pH/Redox Dual-Responsive Drug Delivery System with on-Demand RGD Exposure for Photochemotherapy of Tumors

Yaning Li, Junfang Nie, Jie Dai, Jun Yin, Binbin Huang, Jia Liu, Guoguang Chen, Lili Ren

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Purpose: Nanotechnology has been widely used in antitumor research. The complex physiological environment has brought significant challenges to the field of antitumor micelles. The ideal micelles must not only have an invisible surface to extend the circulation time but must also enhance the retention of drugs and cellular internalization at the tumor. Methods: A graded response micelle (RPPssD@IR780/DOC) was designed to self-assemble by cRGD-poly(β-amino esters)-polyethylene glycol-ss-distearoyl phosphatidylethanolamine (cRGD-PBAE-PEG-ss-DSPE) loaded with docetaxel (DOC) and IR-780 iodide (IR780). The micelles were designed to allow the PEG shell to prolong the blood circulation time in the body and effectively accumulate in the tumor. Subsequently, the acidic microenvironment of the tumor could transform the PBAE to hydrophilic, thereby increasing the size of micelles and exposing cyclic Arg-Gly-Asp (cRGD) peptides to increase the retention and cellular internalization of micelles in the tumor. After tumor cells had captured micelles, the high expression of glutathione in the cells prompted the release of DOC and IR780. Subsequently, the IR780 was stimulated by an 808-nm laser to generate local heat and reactive oxygen species (ROS) to synergize with DOC to treat the tumor. Results: In vitro and in vivo experimental results suggested that RPPssD@IR780/DOC was a potential photochemical effective for the treatment of tumors with non-negligible antitumor activity and good biocompatibility. Conclusion: A dual-response pH/redox delivery system with on-demand RGD exposure was designed to achieve photochemotherapy of tumors with good biosafety and antitumor effects.

Original languageEnglish
Pages (from-to)5621-5639
Number of pages19
JournalInternational Journal of Nanomedicine
Volume17
DOIs
StatePublished - 2022

Keywords

  • drug delivery
  • ligand hidden
  • micelles
  • photo-chemotherapy
  • size variable

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