A Virus-Mimicking pH-Responsive Acetalated Dextran-Based Membrane-Active Polymeric Nanoparticle for Intracellular Delivery of Antitumor Therapeutics

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Wannasarit , S , Wang , S , Figueiredo , P , Trujillo Olvera , C X , Eburnea , F , Simón-Gracia , L , Correia , A , Ding , Y , Teesalu , T , Liu , D , Wiwattanapatapee , R , Santos , H A & Li , W 2019 , ' A Virus-Mimicking pH-Responsive Acetalated Dextran-Based Membrane-Active Polymeric Nanoparticle for Intracellular Delivery of Antitumor Therapeutics ' , Advanced Functional Materials , vol. 29 , no. 51 , 1905352 . https://doi.org/10.1002/adfm.201905352

Title: A Virus-Mimicking pH-Responsive Acetalated Dextran-Based Membrane-Active Polymeric Nanoparticle for Intracellular Delivery of Antitumor Therapeutics
Author: Wannasarit, Saowanee; Wang, Shiqi; Figueiredo, Patricia; Trujillo Olvera, Claudia Ximenia; Eburnea, Francesca; Simón-Gracia, Lorena; Correia, Alexandra; Ding, Yaping; Teesalu, Tambet; Liu, Dongfei; Wiwattanapatapee, Ruedeekorn; Santos, Hélder A.; Li, Wei
Contributor: University of Helsinki, Divisions of Faculty of Pharmacy
University of Helsinki, Divisions of Faculty of Pharmacy
University of Helsinki, Division of Pharmaceutical Chemistry and Technology
University of Helsinki, Nanomedicines and Biomedical Engineering
University of Helsinki, Nanomedicines and Biomedical Engineering
University of Helsinki, Drug Research Program
University of Helsinki, Helsinki One Health (HOH)
University of Helsinki, Division of Pharmaceutical Chemistry and Technology
Date: 2019-12-19
Language: eng
Number of pages: 14
Belongs to series: Advanced Functional Materials
ISSN: 1616-301X
URI: http://hdl.handle.net/10138/321185
Abstract: Achieving cellular internalization and endosomal escape remains a major challenge for many antitumor therapeutics, especially macromolecular drugs. Viral drug carriers are reported for efficient intracellular delivery, but with limited choices of payloads. In this study, a novel polymeric nanoparticle (ADMAP) is developed, resembling the structure and functional features of a virus. ADMAP is synthesized by grafting endosomolytic poly(lauryl methacrylate‐co‐methacrylic acid) on acetalated dextran. The endosomolytic polymer mimics the capsid protein for endosomal escape, and acetalated dextran resembles the viral core for accommodating payloads. After polymer synthesis, the subsequent controlled nanoprecipitation on a microfluidic device yields uniform nanoparticles with high encapsulation efficiency. At late endosomal pH (5.0), the ADMAP particles successfully destabilize endosomal membranes and release the drug payloads synergistically, resulting in a greater therapeutic efficacy compared with that of free anticancer drugs. Further conjugation of a tumor‐penetrating peptide enhances the antitumor efficacy toward 3D spheroids and finally leads to spheroid disintegration. The unique structure along with the synergistic endosomal escape and drug release make ADMAP nanoparticles favorable for intracellular delivery of antitumor therapeutics.
Subject: ADENOVIRUS
CARRIERS
CELL-PENETRATING PEPTIDES
CHALLENGES
DESIGN
DRUG-DELIVERY
EFFICIENT
ENDOSOMAL ESCAPE
INHIBITORS
STRATEGIES
drug delivery
endosomal escape
microfluidics
pH-responsive
polymer nanoparticles
116 Chemical sciences
221 Nano-technology
317 Pharmacy
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