DTX@VTX NPs synergy PD-L1 immune checkpoint nanoinhibitor to reshape immunosuppressive tumor microenvironment for enhancing chemo-immunotherapy

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

Detail(s)

Original languageEnglish
Pages (from-to)7544-7556
Journal / PublicationJournal of Materials Chemistry B
Volume9
Issue number36
Online published11 Aug 2021
Publication statusPublished - 28 Sep 2021

Abstract

Immunosuppressed tumor microenvironment (TME) is a major cause of the low response rate in solid tumor patients during PD-1/PD-L1 checkpoint blockade therapy. In this study, a series of small molecule nanomedicines with a 100% drug loading rate were prepared via the nanoprecipitation method. They were used in synergistic chemo-immunotherapy for 4T1 tumors. Among four PD-L1 small-molecule nanoinhibitors, BMS-1 NP with the best anti-tumor performance was selected to replace the therapeutic PD-L1 antibody. The core-shell small-molecule nanomedicine DTX@VTX NP (DTX: Docetaxel and VTX: VTX-2337 or Motolimod) was used to reverse immunosuppressed TME through the depletion of myeloid-derived suppressor cells (MDSCs) and the polarization of macrophages from an M2-like phenotype to M1-like phenotype. Thus, the frequency of cytotoxic CD8T cells was significantly increased, resulting in an effective attack on cancer cells. Combining BMS-1 NPs with DTX@VTX NPs, synergistic chemo-immunotherapy of 4T1 tumors was performed, and the results indicate that the inhibition rates of primary and rechallenge tumors achieved 90.5% and 94.3%, respectively. These results indicate that DTX@VTX NPs can synergize PD-L1 nanoinhibitor BMS-1 NPs to reshape the immunosuppressive tumor microenvironment for enhancing the anti-tumor effect of chemoimmunotherapy for breast.

Citation Format(s)

DTX@VTX NPs synergy PD-L1 immune checkpoint nanoinhibitor to reshape immunosuppressive tumor microenvironment for enhancing chemo-immunotherapy. / Zhang, Rui; Wan, Yingpeng; Lv, Hongying; Li, Futian; Lee, Chun-Sing.

In: Journal of Materials Chemistry B, Vol. 9, No. 36, 28.09.2021, p. 7544-7556.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review