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A Virus‐Mimicking pH‐Responsive Acetalated Dextran‐Based Membrane‐Active Polymeric Nanoparticle for Intracellular Delivery of Antitumor Therapeutics
Author(s) -
Wannasarit Saowanee,
Wang Shiqi,
Figueiredo Patrícia,
Trujillo Claudia,
Eburnea Francesca,
SimónGracia Lorena,
Correia Alexandra,
Ding Yaping,
Teesalu Tambet,
Liu Dongfei,
Wiwattanapatapee Ruedeekorn,
Santos Hélder A.,
Li Wei
Publication year - 2019
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201905352
Subject(s) - endosome , dextran , intracellular , drug delivery , internalization , biophysics , nanoparticle , materials science , capsid , drug carrier , methacrylate , membrane , macromolecule , polymer , nanotechnology , virus , chemistry , cell , biochemistry , biology , virology , copolymer , composite material
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.