@article{Sepulveda2024,

title = {Influence of structural organization on mucoadhesive properties of poloxamer-hyaluronic acid-based micelles and hydrogels: From molecular modelling to biointerfaces interactions},

author = {Anderson Ferreira Sepulveda and Jéssica Bassi da Silva and Marcos Luciano Bruschi and Margareth KKD Franco and Fabiano Yokaichiya and Giovana Radomille Tófoli and Cíntia Maria Saia Cereda and Anabella Patricia Rosso and Fernando C. Giacomelli and Ana Ligia Scott and Daniele Ribeiro de Araujo},

url = {https://www.sciencedirect.com/science/article/abs/pii/S0927775724013918},

doi = {10.1016/j.colsurfa.2024.134527},

issn = {0927-7757},

year  = {2024},

date = {2024-10-00},

urldate = {2024-10-00},

journal = {Colloids and Surfaces A: Physicochemical and Engineering Aspects},

volume = {698},

publisher = {Elsevier BV},

abstract = {New pharmaceutical formulations have been proposed as strategies to improve transport and provide best conditions to control the drug release rate in specific biological environments, such as mucosa surfaces. Herein, formulations containing binary systems Poloxamer (PL) 407 15 % and PL 338 15 %, combined with hyaluronic acid, carrying the local anesthetic bupivacaine (BVC), were studied by molecular dynamics, while other structural parameters were determined by Dynamic Light Scattering for stablishing relationships with mucoadhesive properties and cytotoxicity evaluation. The binary system PL 407 15 %/PL 338 15 % exhibited a well-organized structural morphology, with more hydrated corona, and increased mucoadhesive properties over mucin layers. After hyaluronic acid (HA) incorporation, it was observed an increase on the force of detachment, possibly due to HA role as a linker among mucin layers independently of PL supramolecular structures. On the other hand, the addition of BVC or HA/BVC into the binary system decreased the force of detachment, as a response of augmented of compactness of these hydrogels caused by desolvation of PO core, showing the influence of all components and their chemical interactions into the structural organization and their biopharmaceutical performance relationships.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rosso2024,

title = {Evaluation of polymersome permeability as a fundamental aspect towards the development of artificial cells and nanofactories},

author = {Anabella P. Rosso and Fernando A. de Oliveira and Philippe Guégan and Eliezer Jager and Fernando C. Giacomelli},

url = {https://www.sciencedirect.com/science/article/abs/pii/S0021979724011196},

doi = {10.1016/j.jcis.2024.05.133},

issn = {0021-9797},

year  = {2024},

date = {2024-10-00},

urldate = {2024-10-00},

journal = {Journal of Colloid and Interface Science},

volume = {671},

pages = {88--99},

publisher = {Elsevier BV},

abstract = {Polymersomes are synthetic vesicles with potential use in healthcare, chemical transformations in confined environment (nanofactories), and in the construction of artificial cells and organelles. In this framework, one of the most important features of such supramolecular structures is the permeability behavior allowing for selective control of mass exchange between the inner and outer compartments. The use of biological and synthetic nanopores in this regard is the most common strategy to impart permeability nevertheless, this typically requires fairly complex strategies to enable porosity. Yet, investigations concerning the permeability of polymer vesicles to different analytes still requires further exploration and, taking these considerations into account, we have detailed investigated the permeability behavior of a variety of polymersomes with regard to different analytes (water, protons, and rhodamine B) which were selected as models for solvents, ions, and small molecules. Polymersomes based on hydrophilic blocks of poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) or PEO (poly(ethylene oxide)) linked to the non-responsive blocks poly[N-(4-isopropylphenylacetamide)ethyl methacrylate] (PPPhA) or poly(methyl methacrylate) (PMMA), or to the stimuli pH-responsive block poly[2-(diisopropylamino)ethyl methacrylate] (PDPA) have been investigated. Interestingly, the produced PEO-based vesicles are notably larger than the ones produced using PHPMA-containing block copolymers. The experimental results reveal that all the vesicles are inherently permeable to some extent with permeability behavior following exponential profiles. Nevertheless, polymersomes based on PMMA as the hydrophobic component were demonstrated to be the least permeable to the small molecule rhodamine B as well as to water. The synthetic vesicles based on the pH-responsive PDPA block exhibited restrictive and notably slow proton permeability as attributed to partial chain protonation upon acidification of the medium. The dye permeability was evidenced to be much slower than ion or solvent diffusion, and in the case of pH-responsive assemblies, it was demonstrated to also depend on the ionic strength of the environment. These findings are understood to be highly relevant towards polymer selection for the production of synthetic vesicles with selective and time-dependent permeability, and it may thus contribute in advancing biomimicry and nanomedicine.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Jäger2024,

title = {Membrane Permeability and Responsiveness Drive Performance: Linking Structural Features with the Antitumor Effectiveness of Doxorubicin-Loaded Stimuli-Triggered Polymersomes},

author = {Eliézer Jäger and Peter Černoch and Martina Vragovic and Lindomar Jose Calumby Albuquerque and Vladimir Sincari and Tomáš Heizer and Alessandro Jäger and Jan Kučka and Olga Šebestová Janoušková and Ewa Pavlova and Luděk Šefc and Fernando C. Giacomelli},

url = {https://pubs.acs.org/doi/full/10.1021/acs.biomac.4c00282},

doi = {10.1021/acs.biomac.4c00282},

issn = {1526-4602},

year  = {2024},

date = {2024-07-08},

urldate = {2024-07-08},

journal = {Biomacromolecules},

volume = {25},

number = {7},

pages = {4192--4202},

publisher = {American Chemical Society (ACS)},

abstract = {The permeability and responsiveness of polymer membranes are absolutely relevant in the design of polymersomes for cargo delivery. Accordingly, we herein correlate the structural features, permeability, and responsiveness of doxorubicin-loaded (DOX-loaded) nonresponsive and stimuli-responsive polymersomes with their in vitro and in vivo antitumor performance. Polymer vesicles were produced using amphiphilic block copolymers containing a hydrophilic poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) segment linked to poly[N-(4-isopropylphenylacetamide)ethyl methacrylate] (PPPhA, nonresponsive block), poly[4-(4,4,5,5-tetra-methyl-1,3,2-dioxaborolan-2-yl)benzyl methacrylate] [PbAPE, reactive oxygen species (ROS)-responsive block], or poly[2-(diisopropylamino)ethyl methacrylate] (PDPA, pH-responsive block). The PDPA-based polymersomes demonstrated outstanding biological performance with antitumor activity notably enhanced compared to their counterparts. We attribute this behavior to a fast-triggered DOX release in acidic tumor environments as induced by pH-responsive polymersome disassembly at pH < 6.8. Possibly, an insufficient ROS concentration in the selected tumor model attenuates the rate of ROS-responsive vesicle degradation, whereas the nonresponsive nature of the PPPhA block remarkably impacts the performance of such potential nanomedicines.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Albuquerque2024,

title = {Nucleic acid delivery to retinal cells using lipopeptides as a potential tool towards ocular gene therapies},

author = {Lindomar J.C. Albuquerque and Fernando A. de Oliveira and Marcelo A. Christoffolete and Michelle Nascimento-Sales and Simone Berger and Ernst Wagner and Ulrich Lächelt and Fernando C. Giacomelli},

url = {https://www.sciencedirect.com/science/article/abs/pii/S0021979723021033},

doi = {10.1016/j.jcis.2023.11.003},

issn = {0021-9797},

year  = {2024},

date = {2024-02-00},

urldate = {2024-02-00},

journal = {Journal of Colloid and Interface Science},

volume = {655},

pages = {346--356},

publisher = {Elsevier BV},

abstract = {We evaluated the use of lipopeptides capable to bind to nucleic acids towards plasmid DNA (pDNA) delivery. The investigations were particularly focused on arising retinal pigment epithelial cells (ARPE-19) as motivated by the considerable number of ocular disorders linked to gene aberrations. The lipopeptides comprised the artificial oligoamino acid succinyl-tetraethylene pentamine (Stp) as well as incorporated lysines, histidines, cysteines, fatty acids, and tyrosine trimers. Regardless of the structural differences, the lipopeptides demonstrated to efficiently condense pDNA at nitrogen-to-phosphate molar ratio (N/P) ≥ 6. Spheric nanoparticles were observed by cryo-TEM and dynamic light scattering determined hydrodynamic sizes ranging from 50 to 130 nm. The biological assays evidenced highly efficient pDNA delivery with a lower degree of cytotoxicity compared to the well-known transfecting agent linear polyethylenimine (LPEI). Although more efficient than LPEI, cysteine-containing carriers were demonstrated to be less efficient than the other counterparts possibly due to exceeding polyplex stabilization via disulfide cross links, which could hamper pDNA unpacking at the target site. Therefore, clearly a balance between complex stability and cargo release should be taken into account to optimize the transfection efficiency of the non-viral vectors. The gene transfer activity in ARPE-19 cells suggests the applicability of this kind of carrier for ocular treatments based on retinal gene delivery.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Santos2023,

title = {Amphiphilic star copolymers composed of curcumin core for bacterial inactivation},

author = {Madson RE Santos and Clara LB Fidelis and Flávia S Zandonadi and Fernando C. Giacomelli and Maria Isabel Felisberti},

url = {https://scijournals.onlinelibrary.wiley.com/doi/abs/10.1002/pi.6565},

doi = {10.1002/pi.6565},

issn = {1097-0126},

year  = {2024},

date = {2024-01-00},

urldate = {2024-01-00},

journal = {Polymer International},

volume = {73},

number = {1},

pages = {21--29},

publisher = {Wiley},

abstract = {Polymeric materials with antimicrobial properties hold the potential to be the next generation of therapeutics. This work reports the preparation of amphiphilic and star-like copolymers through arm-first and reversible addition–fragmentation chain transfer polymerization. The copolymers composed of poly(dimethylamine ethyl methacrylate) (PDMAEMA) as the arms and poly(curcumin dimethacrylate) (PCDMA) as the crosslinked core presented a well-controlled amphiphilic structure with low dispersity values (Ð = 1.15). Varying the [CDMA]:[PDMAEMA] molar ratios (4, 6 and 8) led to a significant increase in the molar mass (153, 688 and 1550 kDa), particle size (33, 90 and 105 nm) and the average number of PDMAEMA arms anchored to the curcumin-based core (12, 52 and 125 arms), as determined by dynamic and static light scattering. The antimicrobial activity of cationic PDMAEMA40-co-PCDMAcore was tested against Escherichia coli in the absence of light and under white light to investigate the photodynamic activity of the copolymers. The results demonstrated a concentration dependence but no additional effect under light irradiation. SEM imaging and live/dead assays revealed extensive membrane damage, evidencing a membrane-disruption mechanism. HeLa viability assays demonstrated that at 1 mg mL−1, 80 ± 10% of the cells demonstrated metabolic activity after 24 h. © 2023 Society of Industrial Chemistry.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ribeiro2023,

title = {Polyethylenimine as a Versatile Simultaneous Reducing and Stabilizing Agent Enabling One-Pot Synthesis of Transition-Metal Nanoparticles: Fundamental Aspects and Practical Implications},

author = {Caroline A. S. Ribeiro and Karine Panico and Tamara J. Handajevsky and Fernanda Dias da Silva and Ismael C. Bellettini and Ewa Pavlova and Fernando C. Giacomelli},

url = {https://pubs.acs.org/doi/abs/10.1021/acs.langmuir.3c02538},

doi = {10.1021/acs.langmuir.3c02538},

issn = {1520-5827},

year  = {2023},

date = {2023-12-05},

urldate = {2023-12-05},

journal = {Langmuir},

volume = {39},

number = {48},

pages = {17353--17365},

publisher = {American Chemical Society (ACS)},

abstract = {The large surface area of metallic nanoparticles provides them with particular optical, chemical, and biological properties, accordingly enabling their use in a wide array of applications. In this regard, facile and fast synthetic approaches are desirable for ready-to-use functional materials. Following early investigations focused on the direct synthesis of polymer-coated gold nanoparticles, we herein demonstrate that such a strategy can be used to manufacture different types of d-block transition-metal nanoparticles via a one-pot method in aqueous media and mild temperature conditions. Gold (Au3+), palladium (Pd2+), and silver (Ag+) ions could be reduced using only polyethylenimine (PEI) or PEI derivatives acting simultaneously as a reducing and stabilizing agent and without the aid of any other external agent. The process gave rise, for instance, to Pd urchin-like nanostructures with a large surface area which confers to them outstanding catalytic performance compared to AuNPs and AgNPs produced using the same strategy. The polymer-stabilized AgNPs were demonstrated to be biocide against a variety of microorganisms, although AuNPs and PdNPs do not hold such an attribute at least in the probed concentration range. These findings may provide significant advances toward the practical, facile, and ready-to-use manufacturing of transition-metal nanoparticles for a myriad of applications.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{deOliveira2023,

title = {Balancing gene transfection and cytotoxicity of nucleic acid carriers with focus on ocular and hepatic disorders: evaluation of hydrophobic and hydrophilic polyethyleneimine derivatives},

author = {Fernando A. de Oliveira and Lindomar J. C. Albuquerque and Michelle Nascimento-Sales and Marcelo A. Christoffolete and Ismael C. Bellettini and Fernando C. Giacomelli},

url = {https://pubs.rsc.org/en/content/articlelanding/2023/tb/d3tb00477e/unauth},

doi = {10.1039/d3tb00477e},

issn = {2050-7518},

year  = {2023},

date = {2023-05-24},

urldate = {2023-05-24},

journal = {J. Mater. Chem. B},

volume = {11},

number = {20},

pages = {4556--4571},

publisher = {Royal Society of Chemistry (RSC)},

abstract = {Polyethyleneimine (PEI) derivatives substituted by lactose, succinic acid or alkyl domains were evaluated as nonviral gene delivery vectors towards balancing gene transfection and cytotoxicity. The investigations were focused on pDNA transfection into arising retinal pigment epithelia (ARPE-19) and human hepatocellular carcinoma (HepG2) cell lines. The first mentioned cell line was chosen as motivated by the non-negligible number of ocular disorders linked to gene aberrations, whereas the second one is a cell line overexpressing the asialoglycoprotein receptor (ASGP-R), which can bind to galactose residues. The presence of short alkyl domains (C4 and C6), and particularly the succinylation of the PEI chains, improved the biological outputs of the gene vectors. The presence of hydrophobic units possibly enhances lytic activity, whereas the incorporation of succinic acid slightly reduces polymer–DNA interaction strength, thereby enabling more efficient intracellular unpacking and cargo release. Succinylation is also supposed to decrease cytotoxicity and avoid protein adsorption to the polyplexes. The presence of long carbon chains (for instance, C12) nevertheless, results in higher levels of cytotoxicity and respective lower transfection rates. The sugar-decorated polyplexes are overall less cytotoxic, but the presence of lactose moieties also leads to larger polyplexes and notably weak polymer–DNA binding, which compromise the transfection efficiency. Yet, along with the presence of short lytic alkyl domains, the double-substitution of PEI synergistically boosts gene transfection probably due to the uptake of higher DNA and polymer amounts without cell damage. Overall, the experimental data suggest that ocular and hepatic gene therapies may be potentialized by fine-tuning the hydrophobic-to-hydrophilic balance, and succinic acid is a favorable motif for the modification of PEI.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{deOliveira2023c,

title = {Role of Membrane Features on the Permeability Behavior of Polymersomes and the Potential Impacts on Drug Encapsulation and Release},

author = {Fernando A. de Oliveira and Carin Cristina da Silva Batista and Peter Černoch and Vladimir Sincari and Alessandro Jäger and Eliézer Jäger and Fernando C. Giacomelli},

url = {https://pubs.acs.org/doi/abs/10.1021/acs.biomac.3c00162},

doi = {10.1021/acs.biomac.3c00162},

issn = {1526-4602},

year  = {2023},

date = {2023-05-08},

urldate = {2023-05-08},

journal = {Biomacromolecules},

volume = {24},

number = {5},

pages = {2291--2300},

publisher = {American Chemical Society (ACS)},

abstract = {Self-assembled bilayer structures such as those produced from amphiphilic block copolymers (polymersomes) are potentially useful in a wide array of applications including the production of artificial cells and organelles, nanoreactors, and delivery systems. These constructs are of important fundamental interest, and they are also frequently considered toward advances in bionanotechnology and nanomedicine. In this framework, membrane permeability is perhaps the most important property of such functional materials. Having in mind these considerations, we herein report the manufacturing of intrinsically permeable polymersomes produced using block copolymers comprising poly[2-(diisopropylamino)-ethyl methacrylate] (PDPA) as the hydrophobic segment. Although being water insoluble at pH 7.4, its pKa(PDPA) ∼ 6.8 leads to the presence of a fraction of protonated amino groups close to the physiological pH, thus conducting the formation of relatively swollen hydrophobic segments. Rhodamine B-loaded vesicles demonstrated that this feature confers inherent permeability to the polymeric membrane, which can still be modulated to some extent by the solution pH. Indeed, even at higher pH values where the PDPA chains are fully deprotonated, the experiments demonstrate that the membranes remain permeable. While membrane permeability can be, for instance, regulated by introducing membrane proteins and DNA nanopores, examples of membrane-forming polymers with intrinsic permeability have been seldom reported so far, and the possibility to regulate the flow of chemicals in these compartments by tuning block copolymer features and ambient conditions is of due relevance. The permeable nature of PDPA membranes possibly applies to a wide array of small molecules, and these findings can in principle be translocated to a variety of disparate bio-related applications.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{deOliveira2023b,

title = {Tuning the morphology of block copolymer-based pH-triggered nanoplatforms as driven by changes in molecular weight and protocol of manufacturing},

author = {Fernando A. de Oliveira and Carin C. S. Batista and Lindomar J. C. Albuquerque and Peter Černoch and Miloš Steinhart and Vladimir Sincari and Alessandro Jager and Eliezer Jager and Fernando C. Giacomelli},

url = {https://www.sciencedirect.com/science/article/abs/pii/S0021979722022834},

doi = {10.1016/j.jcis.2022.12.129},

issn = {0021-9797},

year  = {2023},

date = {2023-04-00},

urldate = {2023-04-00},

journal = {Journal of Colloid and Interface Science},

volume = {635},

pages = {406--416},

publisher = {Elsevier BV},

abstract = {The ability to tune size and morphology of self-assemblies is particularly relevant in the development of delivery systems. By tailoring such structural parameters, one can provide larger cargo spaces or produce nanocarriers that can be loaded by hydrophilic and hydrophobic molecules starting ideally from the same polymer building unit. We herein demonstrate that the morphology of block copolymer-based pH-triggered nanoplatforms produced from poly(2-methyl-2-oxazoline)m-b-poly[2-(diisopropylamino)-ethyl methacrylate]n (PMeOxm-b-PDPAn) is remarkably influenced by the overall molecular weight of the block copolymer, and by the selected method used to produce the self-assemblies. Polymeric vesicles were produced by nanoprecipitation using a block copolymer of relatively low molecular weight (Mn ∼ 10 kg.mol−1). Very exciting though, despite the high hydrophobic weight ratio (wPDPA > 0.70), this method conducted to the formation of core–shell nanoparticles when block copolymers of higher molecular weight were used, thus suggesting that the fast (few seconds) self-assembly procedure is controlled by kinetics rather than thermodynamics. We further demonstrated the formation of vesicular structures using longer chains via the solvent-switch approach when the “switching” to the bad solvent is performed in a time scale of a few hours (approximately 3 hs). We accordingly demonstrate that using fairly simple methods one can easily tailor the morphology of such block copolymer self-assemblies, thereby producing a variety of structurally different pH-triggered nanoplatforms via a kinetic or thermodynamically-controlled process. This is certainly attractive towards the development of nanotechnology-based cargo delivery systems.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Du2023,

title = {Engineering of ion permeable planar membranes and polymersomes based on β-cyclodextrin-cored star copolymers},

author = {Haiqin Du and Sandra Kalem and Cécile Huin and Nicolas Illy and Guillaume Tresset and Fernando C. Giacomelli and Philippe Guégan},

url = {https://www.sciencedirect.com/science/article/abs/pii/S0021979722017386},

doi = {10.1016/j.jcis.2022.09.147},

issn = {0021-9797},

year  = {2023},

date = {2023-01-00},

urldate = {2023-01-00},

journal = {Journal of Colloid and Interface Science},

volume = {630},

pages = {465--476},

publisher = {Elsevier BV},

abstract = {For polymersome-based nanoreactor purposes, we herein present the synthesis and characterization of well-defined star amphiphilic copolymers composed of a beta-cyclodextrin (βCD) core and seven poly(butylene oxide)-block-polyglycidol (PBO-PGL) arms per side (βCD-(PBO-PGL)14). The self-assembly behavior of 14-armed βCD-(PBO-PGL)14 and PGL-PBO-PGL (linear analogues without the βCD segment) was investigated using scattering techniques for comparison. The morphologies, including vesicles and micelles, are governed by the hydrophobic-to-hydrophilic (weight) ratio, regardless of the polymer architecture (linear or star). Interestingly, despite notable differences in polymer conformation, the produced supramolecular structures were evidenced to be fairly similar on the structural point of view. We subsequently investigated the ion permeability of the membranes of the self-assemblies focusing on the impact of the presence of βCD. The results demonstrated that the βCD-containing vesicular membranes are less permeable to H+, compared with βCD-free vesicular membranes. The presence of βCD in planar membranes also influences the K+Cl− permeability to some extent. Thus, βCD-containing membranes can be considered as potential candidates in designing nano-containers towards applications where precise changes in environmental pH are required.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Batista2022,

title = {Protein coronas coating polymer-stabilized silver nanocolloids attenuate cytotoxicity with minor effects on antimicrobial performance},

author = {Carin C.S. Batista and Karine Panico and Jiří Trousil and Olga Janoušková and Carlos Eduardo de Castro and Petr Štěpánek and Fernando C. Giacomelli},

url = {https://www.sciencedirect.com/science/article/abs/pii/S0927776522004611},

doi = {10.1016/j.colsurfb.2022.112778},

issn = {0927-7765},

year  = {2022},

date = {2022-10-00},

urldate = {2022-10-00},

journal = {Colloids and Surfaces B: Biointerfaces},

volume = {218},

publisher = {Elsevier BV},

abstract = {Silver nanoparticles are versatile platforms with a variety of applications in the biomedical field. In this framework, their presence in biological media inevitably leads to the interaction with proteins thus conducting to the formation of biomolecular coronas. This feature alters the identity of the nanomaterial and may affect many biological events. These considerations motivated the investigation of protein adsorption onto the surface of polymer-stabilized AgNPs. The metallic colloids were coated by polyethyleneimine (PEI), polyvinylpyrrolidone (PVP), and poly(2-vinyl pyridine)-b-poly(ethylene oxide) (PEO-b-P2VP), and nanoparticle-protein interaction was probed by using a library of analytical techniques. The experimental data revealed a higher extent of protein adsorption at the surface of AgNPs@PVP whereas PEO-b-P2VP coating conducted to the least amount. The main component of the protein coronas was evidenced to be bovine serum albumin (BSA), which is indeed the protein at the highest abundancy in the model biological media. We have further demonstrated reduced cytotoxicity of the silver colloids coated by biomolecular coronas as compared to the pristine counterparts. Nevertheless, the protein coatings did not notably reduce the antimicrobial performance of the polymer-stabilized AgNPs. Accordingly, although the protein-repelling property is frequently targeted towards longer in vivo circulation of nanoparticles, we herein underline that protein coatings, which are commonly treated as artifacts to be avoided, may indeed enhance the biological performance of nanomaterials. These findings are expected to be highly relevant in the design of polymer-stabilized metallic colloids intended to be used in healthcare.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{deOliveira2022,

title = {Reduced cytotoxicity of nanomaterials driven by nano-bio interactions: Case study of single protein coronas enveloping polymersomes},

author = {Fernando A. de Oliveira and Lindomar J.C. Albuquerque and Carlos E. Castro and Karin A. Riske and Ismael C. Bellettini and Fernando C. Giacomelli},

url = {https://www.sciencedirect.com/science/article/abs/pii/S0927776522000704},

doi = {10.1016/j.colsurfb.2022.112387},

issn = {0927-7765},

year  = {2022},

date = {2022-05-00},

urldate = {2022-05-00},

journal = {Colloids and Surfaces B: Biointerfaces},

volume = {213},

publisher = {Elsevier BV},

abstract = {The protein adsorption onto poly(acrylic acid)-block-polystyrene (PAA22-b-PS144) polymersomes has been investigated with regard to structural features, thermodynamic aspects and biological consequences. The light scattering measurements revealed the formation of protein coronas enveloping the polymeric capsules regardless of the chemical nature of the biomacromolecules. The experiments were conducted by using lysozyme, immunoglobulin G - IgG and bovine serum albumin - BSA as model proteins due to their differences concerning size and residual surface charge at physiological pH. The protein adsorption was further confirmed by isothermal titration calorimetry, and the experimental data suggest that the phenomenon is mainly governed by hydrogen bonding and van der Waals interactions. The pre-existing protein layer via the pre-incubation in protein environments notably attenuates the cytotoxicity of the nanomaterial compared to the pristine counterparts. This approach can possibly be extended to different types of assemblies when intermolecular interactions are able to induce protein adsorption and the development of protein coronas around nanoparticles. Such fairly simple method may be convenient to engineer safer nanomaterials towards a variety of biomedical applications when the nanotoxicity is an issue. Additionally, the strategy can possibly be used to tailor the surface properties of nanoparticles by adsorbing specific proteins for targeting purposes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{A.S.Ribeiro2022,

title = {Ready-to-use room temperature one-pot synthesis of surface-decorated gold nanoparticles with targeting attributes},

author = {Caroline A. S. Ribeiro and Lindomar J. C. Albuquerque and Carlos E. de Castro and Rodrigo M. Pereira and Brunno L. Albuquerque and Ewa Pavlova and Luiza Gabriela Schlüter and Bruno L. Batista and Ismael C. Bellettini and Fernando C. Giacomelli},

url = {https://www.sciencedirect.com/science/article/abs/pii/S0021979722001655},

doi = {10.1016/j.jcis.2022.01.145},

issn = {0021-9797},

year  = {2022},

date = {2022-05-00},

urldate = {2022-05-00},

journal = {Journal of Colloid and Interface Science},

volume = {614},

pages = {489--501},

publisher = {Elsevier BV},

abstract = {Gold nanoparticles (AuNPs) can be used in diagnostic and therapeutic applications. The development of facile and fast synthetic approaches is accordingly desirable towards ready-to-use biomedical materials. We report a practical one-pot method for the synthesis in aqueous media and room temperature of surface-decorated AuNPs with enhanced biological responses. The gold ions could be reduced using only polyethyleneimine (PEI) derivatives containing sugar and-or alkyl chains acting simultaneously as reducing and stabilizing agent, without the aid of any other mediator. The process is possibly potentialized by the presence of the amino groups in the polymer chains which further confer colloidal stability. The kinetics of AuNPs nucleation and growth depends on the chemical nature of the polymer chains. Particularly, the presence of lactose moieties conjugated to the PEI chains conducted to surface-decorated AuNPs with low cytotoxicity that are remarkably faster uptaken by HepG2 cells. These cells overexpress asialoglycoprotein (ASGP-R), a galactose receptor. These findings may kick off significant advances towards the practical and ready-to-use manufacturing of functionalized AuNPs towards cell-targeting since the methodology is applicable for a large variety of other ligands that can be conjugated to the same polymer chains.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Frizon2021,

title = {Synthesis of cholesterol containing unsymmetrical dimers: a new series of liquid crystals},

author = {Tiago E. A. Frizon and André A. Vieira and Fernando C. Giacomelli and Rodrigo Cercená and Alexandre Dal Bó and Eduardo Zapp and Eduardo Junca and Antônio A. Chepluki and Cassiano D. Tomasi and Luiz B. Ribeiro and Sumbal Saba and Jamal Rafique},

url = {https://www.tandfonline.com/doi/abs/10.1080/02678292.2021.2007424},

doi = {10.1080/02678292.2021.2007424},

issn = {1366-5855},

year  = {2022},

date = {2022-04-09},

urldate = {2022-04-09},

journal = {Liquid Crystals},

volume = {49},

number = {5},

pages = {758--768},

publisher = {Informa UK Limited},

abstract = {We report an efficient and practical procedure for the synthesis of cholesterol containing unsymmetrical liquid crystals dimers. Liquid crystalline and thermal properties were studied by POM, TGA, DSC, and SAXS analysis. All final products (3a-d) presented liquid crystal properties. The presence of smectic (compounds 3a, 3b, and 3d) and chiral nematic (3 c) mesophases evidenced by polarised optical microscopy (POM) and further confirmed by small-angle X-ray scattering (SAXS) analyses. The compound 3 c remains supercooled until room temperature and presented enantiotropic mesomorphism at a low temperature. This characteristic of organisation and mesomorphism at room temperature makes compound 3 c an ideal candidate for technological applications. The SAXS analyses further suggest possibly the presence of smectic clusters within the nematic liquid crystalline phase. All compounds presented high thermal stability at around 300°C when tested for their thermal properties. The highest occupied molecular orbital (HOMO) energies were estimated from cyclic voltammetry (CV) and used together with the optical absorption measurements to determine the band gap and lowest unoccupied molecular orbital (LUMO) energies. The values obtained were: HOMO (–5.81 to – 6.03 eV), LUMO (–1.53 to – 2.12 eV), and band gap (3.88 to 4.28 eV).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{deOliveira2021b,

title = {Current Designs of Polymeric Platforms Towards the Delivery of Nucleic Acids Inside the Cells with Focus on Polyethylenimine},

author = {Fernando A. de Oliveira and Lindomar J.C. Albuquerque and Gwendoline Delecourt and Véronique Bennevault and Philippe Guégan and Fernando C. Giacomelli},

url = {https://www.ingentaconnect.com/content/ben/cgt/2021/00000021/00000005/art00006},

doi = {10.2174/1566523221666210705130238},

issn = {1566-5232},

year  = {2021},

date = {2021-12-23},

urldate = {2021-12-23},

journal = {CGT},

volume = {21},

number = {5},

pages = {431--451},

publisher = {Bentham Science Publishers Ltd.},

abstract = {Background: Gene delivery is a promising technology for treating diseases linked to abnormal gene expression. Since nucleic acids are the therapeutic entities in such approach, a transfecting vector is required because the macromolecules are not able to efficiently enter the cells by themselves. Viral vectors have been evidenced to be highly effective in this context; however, they suffer from fundamental drawbacks, such as the ability to stimulate immune responses. The development of synthetic vectors has accordingly emerged as an alternative.



Objectives: Gene delivery by using non-viral vectors is a multi-step process that poses many challenges, either regarding the extracellular or intracellular media. We explore the delivery pathway and afterwards, we review the main classes of non-viral gene delivery vectors. We further focus on the progresses concerning polyethylenimine-based polymer-nucleic acid polyplexes, which have emerged as one of the most efficient systems for delivering genetic material inside the cells.



Discussion: The complexity of the whole transfection pathway, along with a lack of fundamental understanding, particularly regarding the intracellular trafficking of nucleic acids complexed to non-viral vectors, probably justifies the current (beginning of 2021) limited number of formulations that have progressed to clinical trials. Truly, successful medical developments still require a lot of basic research.



Conclusion: Advances in macromolecular chemistry and high-resolution imaging techniques will be useful to understand fundamental aspects towards further optimizations and future applications. More investigations concerning the dynamics, thermodynamics and structural parameters of polyplexes would be valuable since they can be connected to the different levels of transfection efficiency hitherto evidenced.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fuentes-García2021,

title = {Sonochemical route for mesoporous silica-coated magnetic nanoparticles towards pH-triggered drug delivery system},

author = {Jesús Antonio Fuentes-García and Alex Carvalho Alavarse and Carlos Eduardo de Castro and Fernando C. Giacomelli and Manuel Ricardo Ibarra and Jean-Jacques Bonvent and Gerardo Fabián Goya},

url = {https://www.sciencedirect.com/science/article/pii/S2238785421008395},

doi = {10.1016/j.jmrt.2021.08.014},

issn = {2238-7854},

year  = {2021},

date = {2021-11-00},

urldate = {2021-11-00},

journal = {Journal of Materials Research and Technology},

volume = {15},

pages = {52--67},

publisher = {Elsevier BV},

abstract = {This work reports a pH-triggered release system based on core@shell mesoporous magnetic nanoparticles (MNP@mSiO2) obtained using a simple and rapid ultrasound-assisted method. Performed characterization reveals magnetic cores of Fe2.9Mn0.1O4 (38 ± 6 nm) and specific loss power values adequate for hyperthermia (463 W/g), surrounded by a mesoporous silica shell (10 ± 2 nm) with large surface area (269 m2 g-1) functionalized with hydroxyl groups (-OH). MNP@mSiO2 were loaded with DOX and amino-silane grops, providing pH-triggered DOX release at acidic environments, driving by dipolar intermolecular interactions. The experimental DOX release kinetics at pH 5.5, 6.6 and 7.4 were determined and adjusted to Gompertz dissolution model (Nash–Sutcliffe efficiency coefficient (NSE>0.9)), where the only strongly pH-dependent variable is the percentage of DOX released. The pH-triggered response observed in the system was ~20% of the DOX loaded into the MNP@mSiO2 is released at pH 6.6 or 7.4, whereas up to 80 wt% is released at pH 5.5. Time to 50% of release and dissociation rate of the system remaining constant, suggesting no-pH influence on these parameters. The biological assays highlight negligible hemolytic effect and cytocompatibility of the hybrid material, pointing out the potential use of MNP@mSiO2 as a magnetic driven drug delivery system with pH-triggered drug release kinetics at acidic environments. These results probe the feasibility of sonochemical methods in the elaboration of biocompatible and controlled properties nanomaterials for drug release applications, with the advantage of accurately responses predictions by mathematical model and using minimal processing steps or laboratory equipment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Batista2021,

title = {Microfluidic-assisted synthesis of uniform polymer-stabilized silver colloids},

author = {Carin C.S. Batista and Alessandro Jäger and Brunno L. Albuquerque and Ewa Pavlova and Petr Stepánek and Fernando C. Giacomelli},

url = {https://www.sciencedirect.com/science/article/abs/pii/S0927775721003071},

doi = {10.1016/j.colsurfa.2021.126438},

issn = {0927-7757},

year  = {2021},

date = {2021-06-00},

urldate = {2021-06-00},

journal = {Colloids and Surfaces A: Physicochemical and Engineering Aspects},

volume = {618},

publisher = {Elsevier BV},

abstract = {We report the controlled synthesis of polymer-stabilized silver nanoparticles (AgNPs) by using microfluidic devices. The microfluidic-based method enabled the preparation of sub-50 nm AgNPs which are much more homogenous compared to those produced in batch reactors where the control over flow and mixing conditions was not performed. The concentration of the silver precursor (silver nitrate - AgNO3) can be tuned to reach smaller or larger nanoparticles, although within a fairly narrow range. Regardless of the polymeric shell, the reducing agent concentration influences the size and polydispersity of the manufactured silver colloids, and relatively lower amounts allow for the manufacturing of more homogeneous nanoparticles. Notably, the use of the block copolymer PEO-b-P2VP as stabilizing agent leads to larger nanoparticles (23–51 nm) compared to those stabilized by PVP (7–14 nm) as possibly linked to different arrangements of the polymer chains at the interface between the precursor solutions. The produced AgNPs are highly uniform, with size distribution width influenced by the polymer concentration (FWHM < 100 nm were determined at higher concentrations), although this variable does not have a distinguished effect on the final size of the manufactured colloids. Overall, we provide relevant new knowledge within the framework of polymer-stabilized AgNPs since a variety of other polymer chains can be probed, possibly with different outcomes regarding the final particle size. The reported findings can thus guide to significant advances towards the manufacturing of highly homogeneous polymer-coated metallic colloids, particularly when a target size is required.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Černoch2021,

title = {Engineering of pH-triggered nanoplatforms based on novel poly(2-methyl-2-oxazoline)-\textit{b}-poly[2-(diisopropylamino)ethyl methacrylate] diblock copolymers with tunable morphologies for biomedical applications},

author = {Peter Černoch and Alessandro Jager and Zulfiya Černochová and Vladimir Sincari and Lindomar J. C. Albuquerque and Rafal Konefal and Ewa Pavlova and Fernando C. Giacomelli and Eliezer Jager},

url = {https://pubs.rsc.org/en/content/articlelanding/2021/py/d1py00141h/unauth},

doi = {10.1039/d1py00141h},

issn = {1759-9962},

year  = {2021},

date = {2021-05-18},

urldate = {2021-05-18},

journal = {Polym. Chem.},

volume = {12},

number = {19},

pages = {2868--2880},

publisher = {Royal Society of Chemistry (RSC)},

abstract = {A two-step synthetic approach via the combination of living cationic ring-opening (CROP) and reversible addition–fragmentation chain transfer (RAFT) polymerization techniques was used to produce novel amphiphilic block copolymers based on the water-soluble poly(2-methyl-2-oxazoline) (PMeOx), which holds protein repelling properties, linked to the hydrophilic–hydrophobic pH-responsive block poly[2-(diisopropylamino)ethyl methacrylate] (PDPA). Hydrodynamic flow focusing nanoprecipitation microfluidics (MF) was further employed to manufacture block copolymer self-assemblies. Interestingly, although all the synthesized macromolecules contained higher amounts of the pH-responsive segment, the microfluidic approach allowed the manufacturing of core–shell micelles and polymersomes. The morphology seems to be driven by the overall molecular weight of the block copolymers rather than by the hydrophilic-to-hydrophobic weight ratio. Longer and shorter amphiphilic chains enabled the manufacturing of core–shell assemblies and polymeric vesicles, respectively. The use of PMeOx and PDPA blocks confers serum stability and pH-responsive behavior to the nanoparticles in a pH window which is particularly useful for tumour detection and therapy. The self-assembled nanostructures are non-toxic even at fairly high polymer concentrations. All these features therefore can be useful in the design of pH-triggered nanoplatforms of distinct morphologies towards a variety of biomedical applications, for instance, the loading and delivery of hydrophobic and hydrophilic therapeutics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Albuquerque2021,

title = {pH-responsive polymersome-mediated delivery of doxorubicin into tumor sites enhances the therapeutic efficacy and reduces cardiotoxic effects},

author = {Lindomar J.C. Albuquerque and Vladimir Sincari and Alessandro Jäger and Jan Kucka and Jana Humajova and Jan Pankrac and Petr Paral and Tomas Heizer and Olga Janouškova and Irina Davidovich and Yeshayahu Talmon and Pavla Pouckova and Petr Štěpánek and Ludek Sefc and Martin Hruby and Fernando C. Giacomelli and Eliézer Jäger},

url = {https://www.sciencedirect.com/science/article/abs/pii/S0168365921001243},

doi = {10.1016/j.jconrel.2021.03.013},

issn = {0168-3659},

year  = {2021},

date = {2021-04-00},

urldate = {2021-04-00},

journal = {Journal of Controlled Release},

volume = {332},

pages = {529--538},

publisher = {Elsevier BV},

abstract = {The delivery of therapeutics into sites of action by using cargo-delivery platforms potentially minimizes their premature degradation and fast clearance from the bloodstream. Additionally, drug-loaded stimuli-responsive supramolecular assemblies can be produced to respond to the inherent features of tumor microenvironments, such as extracellular acidosis. We report in this framework the use of pH-responsive polymersomes (PSs) manufactured using poly([N-(2-hydroxypropyl)] methacrylamide)35-b-poly[2-(diisopropylamino)ethyl methacrylate]75 as the building unit (PHPMA35-b-PDPA75). The self-assemblies were produced with desired size towards long circulation time and tumor accumulation (hydrodynamic diameter - DH ~ 100 nm), and they could be successfully loaded with 10% w/w DOX (doxorubicin), while maintaining colloidal stability. The DOX loaded amount is presumably mainly burst-released at the acidic microenvironment of tumors thanks to the pH-switchable property of PDPA (pKa ~ 6.8), while reduced drug leakage has been monitored in pH 7.4. Compared to the administration of free DOX, the drug-loaded supramolecular structures greatly enhanced the therapeutic efficacy with effective growth inhibition of EL4 lymphoma tumor model and 100% survival rate in female C57BL/6 black mice over 40 days. The approach also led to reduced cardiotoxic effect. These features highlight the potential application of such nanotechnology-based treatment in a variety of cancer therapies where low local pH is commonly found, and emphasize PHPMA-based nanomedicines as an alternative to PEGylated formulations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{deCastro2021,

title = {Evidence of protein coronas around soft nanoparticles regardless of the chemical nature of the outer surface: structural features and biological consequences},

author = {Carlos E. de Castro and Karine Panico and Lucas M. Stangherlin and Lindomar J. C. Albuquerque and Caroline A. S. Ribeiro and Maria C. C. da Silva and Eliézer Jäger and Fernando C. Giacomelli},

url = {https://pubs.rsc.org/en/content/articlelanding/2021/tb/d0tb02734k/unauth},

doi = {10.1039/d0tb02734k},

issn = {2050-7518},

year  = {2021},

date = {2021-03-04},

urldate = {2021-03-04},

journal = {J. Mater. Chem. B},

volume = {9},

number = {8},

pages = {2073--2083},

publisher = {Royal Society of Chemistry (RSC)},

abstract = {The formation of biomolecular coronas around nanoparticles as soon as they come in contact with biological media is nowadays well accepted. The self-developed biological outer surfaces can affect the targeting capability of the colloidal carriers as well as their cytotoxicity and cellular uptake behavior. In this framework, we explored the structural features and biological consequences of protein coronas around block copolymer assemblies consisting of a common pH-responsive core made by poly[2-(diisopropylamino) ethyl methacrylate] (PDPA) and hydrophilic shells of different chemical natures: zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) or highly hydrophilic poly(ethylene oxide) (PEO) and poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA). We demonstrated the presence of ∼50 nm protein coronas around the nanoparticles regardless of the chemical nature of the polymeric shells. The thickness is understood as the sum of the soft and hard layers and it is the actual interface seen by the cells. Although the soft corona composition is difficult to determine because the proteins are loosely bound to the outer surface of the assemblies, the tightly bound proteins (hard corona) could be identified and quantified. The compositional analysis of the hard corona demonstrated that human serum albumin (HSA), immunoglobulin G (IgG) and fibrinogen are the main components of the protein coronas, and serotransferrin is present particularly in the protein corona of the zwitterionic-stabilized assemblies. The protein coronas substantially reduce the cellular uptake of the colloidal particles due to their increased size and the presence of HSA which is known to reduce nanoparticle–cell adhesion. On the other hand, their existence also reduces the levels of cytotoxicity of the polymeric assemblies, highlighting that protein coronas should not be always understood as artifacts that need to be eliminated due to their positive outputs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}