期刊
ADVANCED FUNCTIONAL MATERIALS
卷 29, 期 51, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201905352
关键词
drug delivery; endosomal escape; microfluidics; pH-responsive; polymer nanoparticles
类别
资金
- Thailand Research Fund under the Royal Golden Jubilee (RGJ) Ph.D. program [PHD/0180/2556]
- European Regional Development Fund [2014-2020.4.01.15-0012]
- Estonian Research Council [PRG230]
- Finnish Cultural Foundation [00190634]
- Academy of Finland [322093]
- HiLIFE Research Funds
- Sigrid Juselius Foundation
- Norwegian Research Council/Nacamed AS
- European Research Council Proof-of-Concept Research Grant [825020]
- Biocenter Finland: Electron Microscopy Unity of the University
- Light Microscopy Unit of the Institute of Biotechnology
- Academy of Finland (AKA) [322093, 322093] Funding Source: Academy of Finland (AKA)
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.
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