cRGD-decorated biodegradable polytyrosine nanoparticles for robust encapsulation and targeted delivery of doxorubicin to colorectal cancer in vivo

Xiaolei Gu, Yaohua Wei, Qianyi Fan, Huanli Sun, Ru Cheng, Zhiyuan Zhong* (Corresponding Author), Chao Deng (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Scopus)

Abstract

The clinical success of nanomedicines demands on the development of simple biodegradable nanocarriers that can efficiently and stably encapsulate chemotherapeutics while quickly release the payloads into target cancer cells. Herein, we report that cRGD-decorated biodegradable polytyrosine nanoparticles (cRGD-PTN) boost encapsulation and targeted delivery of doxorubicin (DOX) to colorectal cancer in vivo. The co-assembly of poly(ethylene glycol)-poly(L-tyrosine) (PEG-PTyr) and cRGD-functionalized PEG-PTyr (mol/mol, 80/20) yielded small-sized cRGD-PTN of 70 nm. Interestingly, cRGD-PTN exhibited an ultra-high DOX encapsulation with drug loading contents ranging from 18.5 to 54.1 wt%. DOX-loaded cRGD-PTN (cRGD-PTN-DOX) was highly stable against dilution, serum, and Triton X-100 surfactant, while quickly released DOX in HCT-116 cancer cells, likely resulting from enzymatic degradation of PTyr. Flow cytometry, confocal microscopy and MTT assays displayed that cRGD-PTN-DOX was efficiently internalized into α v β 5 overexpressing HCT-116 colorectal cancer cells, rapidly released DOX into the nuclei, and induced several folds better antitumor activity than non-targeted PTN-DOX and clinically used liposomal DOX (Lipo-DOX). SPECT/CT imaging revealed strong tumor accumulation of 125 I-labeled cRGD-PTN, which was 2.8-fold higher than 125 I-labeled PTN. Notably, cRGD-PTN-DOX exhibited over 5 times better toleration than Lipo-DOX and significantly more effective inhibition of HCT-116 colorectal tumor than non-targeted PTN-DOX control, affording markedly improved survival rate in HCT-116 tumor-bearing mice with depleting side effects at 6 or 12 mg DOX equiv./kg. cRGD-PTN-DOX with great simplicity, robust drug encapsulation and efficient nucleic drug release appears promising for targeted chemotherapy of colorectal tumor.

Original languageEnglish
Pages (from-to)110-118
Number of pages9
JournalJournal of controlled release
Volume301
DOIs
Publication statusPublished - 10 May 2019
Externally publishedYes

Keywords

  • UT-Hybrid-D
  • Enzyme-responsive
  • Polypeptide
  • SPECT/CT imaging
  • Targeted cancer therapy
  • Biodegradable nanoparticles

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