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Microfluidic-assisted engineering of quasi-monodisperse pH-responsive polymersomes toward advanced platforms for the intracellular delivery of hydrophilic therapeutics
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SYSNO ASEP 0505875 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Microfluidic-assisted engineering of quasi-monodisperse pH-responsive polymersomes toward advanced platforms for the intracellular delivery of hydrophilic therapeutics Author(s) Calumby Albuquerque, Lindomar J. (UMCH-V)
Sincari, Vladimir (UMCH-V) ORCID, RID
Jäger, Alessandro (UMCH-V) RID, ORCID
Konefal, Rafal (UMCH-V) RID, ORCID
Pánek, Jiří (UMCH-V) RID, ORCID
Černoch, Peter (UMCH-V) RID, ORCID
Pavlova, Ewa (UMCH-V) RID
Štěpánek, Petr (UMCH-V) RID, ORCID
Giacomelli, F. C. (BR)
Jäger, Eliezer (UMCH-V) ORCID, RIDSource Title Langmuir. - : American Chemical Society - ISSN 0743-7463
Roč. 35, č. 25 (2019), s. 8363-8372Number of pages 10 s. Language eng - English Country US - United States Keywords block copolymers ; microfluidics ; self-assembled Subject RIV CD - Macromolecular Chemistry OECD category Polymer science R&D Projects GA17-09998S GA ČR - Czech Science Foundation (CSF) TN01000008 GA TA ČR - Technology Agency of the Czech Republic (TA ČR) 8J18FR038 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Limited access Institutional support UMCH-V - RVO:61389013 UT WOS 000473248000020 EID SCOPUS 85067954153 DOI 10.1021/acs.langmuir.9b01009 Annotation The extracellular and subcellular compartments are characterized by specific pH levels that can be modified by pathophysiological states. This scenario encourages the use of environmentally responsive nanomedicines for the treatment of damaged cells. We have engineered doxorubicin (DOX)-loaded pH-responsive polymersomes using poly([N-(2-hydroxypropyl)]methacrylamide)-b-poly[2-(diisopropylamino)ethyl methacrylate] block copolymers (PHPMAm-b-PDPAn). We demonstrate that, by taking advantage of the microfluidic technology, quasi-monodisperse assemblies can be created. This feature is of due relevance because highly uniform nanoparticles commonly exhibit more consistent biodistribution and cellular uptake. We also report that the size of the polymer vesicles can be tuned by playing with the inherent mechanical parameters of the microfluidic protocol. This new knowledge can be used to engineer size-specific nanomedicines for enhanced tumor accumulation if the manufacturing is performed with previous knowledge of tumor characteristics (particularly the degree of vascularity and porosity). The pH-dependent DOX release was further investigated evidencing the ability of polymersome to sustain encapsulated hydrophilic molecules when circulating in physiological environment (pH 7.4). This suggests nonrelevant drug leakage during systemic circulation. On the other hand, polymersome disassembly in slightly acid environments takes place enabling fast DOX release, thereby making the colloidal carriers highly cytotoxic. These features encourage the use of such advanced pH-responsive platforms to target damaged cells while preserving healthy environments during systemic circulation. Workplace Institute of Macromolecular Chemistry Contact Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Year of Publishing 2020 Electronic address https://pubs.acs.org/doi/10.1021/acs.langmuir.9b01009
Number of the records: 1