Zwitterionic-to-cationic charge conversion polyprodrug nanomedicine for enhanced drug delivery

Theranostics. 2020 May 17;10(15):6629-6637. doi: 10.7150/thno.47849. eCollection 2020.

Abstract

Zwitterionic surface modification is a promising strategy for nanomedicines to achieve prolonged circulation time and thus effective tumor accumulation. However, zwitterion modified nanoparticles suffer from reduced cellular internalization efficiency. Methods: A polyprodrug-based nanomedicine with zwitterionic-to-cationic charge conversion ability (denoted as ZTC-NMs) was developed for enhanced chemotherapeutic drug delivery. The polyprodrug consists of pH-responsive poly(carboxybetaine)-like zwitterionic segment and glutathione-responsive camptothecin prodrug segment. Results: The ZTC-NMs combine the advantages of zwitterionic surface and polyprodrug. Compared with conventional zwitterionic surface, the ZTC-NMs can respond to tumor microenvironment and realize ZTC surface charge conversion, thus improve cellular internalization efficiency of the nanomedicines. Conclusions: This ZTC method offers a strategy to promote the drug delivery efficiency and therapeutic efficacy, which is promising for the development of cancer nanomedicines.

Keywords: charge conversion; nanomedicine; polyprodrug; triggered drug release; zwitterionic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Camptothecin / pharmacology*
  • Cations / chemistry*
  • Cell Line, Tumor
  • Drug Delivery Systems / methods*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Nude
  • Nanomedicine
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Polymers / chemistry*
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Cations
  • Polymers
  • Prodrugs
  • Camptothecin