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

Saowanee Wannasarit, Shiqi Wang, Patricia Figueiredo, Claudia Ximenia Trujillo Olvera, Francesca Eburnea, Lorena Simón-Gracia, Alexandra Correia, Yaping Ding, Tambet Teesalu, Dongfei Liu, Ruedeekorn Wiwattanapatapee, Hélder A. Santos, Wei Li

Research output: Contribution to journalArticleScientificpeer-review

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.
Original languageEnglish
Article number1905352
JournalAdvanced Functional Materials
Volume29
Issue number51
Number of pages14
ISSN1616-301X
DOIs
Publication statusPublished - 19 Dec 2019
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 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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