Molecular programming of biodegradable nanoworms via ionically induced morphology switch toward asymmetric therapeutic carriers

Shoupeng Cao, Jingxin Shao, Yifeng Xia, Hailong Che, Zhiyuan Zhong, Fenghua Meng, Jan C.M. van Hest (Corresponding author), Loai K.E.A. Abdelmohsen (Corresponding author), David S. Williams

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)
48 Downloads (Pure)

Abstract

Engineering biodegradable nanostructures with precise morphological characteristics is a key objective in nanomedicine. In particular, asymmetric (i.e., nonspherical) nanoparticles are desirable due to the advantageous effects of shape in a biomedical context. Using molecular engineering, it is possible to program unique morphological features into the self-assembly of block copolymers (BCPs). However, the criteria of biocompatibility and scalability limit progress due to the prevalence of nondegradable components and the use of toxic solvents during fabrication. To address this shortfall, a robust strategy for the fabrication of morphologically asymmetric nanoworms, comprising biodegradable BCPs, has been developed. Modular BCPs comprising poly (ethylene glycol)-block-poly(caprolactone-gradient-trimethylene carbonate) (PEG−PCLgTMC), with a terminal chain of quaternary ammonium-TMC (PTMC-Q), undergo self-assembly via direct hydration into well-defined nanostructures. By controlling the solution ionic strength during hydration, particle morphology switches from spherical micelles to nanoworms (of varying aspect ratio). This ionically-induced switch is driven by modulation of chain packing with salts screening interchain repulsions, leading to micelle elongation. Nanoworms can be loaded with cytotoxic cargo (e.g., doxorubicin) at high efficiency, preferentially interact with cancer cells, and increase tumor penetration. This work showcases the ability to program assembly of BCPs and the potential of asymmetric nanosystems in anticancer drug delivery.

Original languageEnglish
Article number1901849
Number of pages8
JournalSmall
Volume15
Issue number38
DOIs
Publication statusPublished - 1 Sep 2019

Keywords

  • drug delivery
  • nanomedicine
  • nanostructures
  • self-assembly

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