Dataset Information

An erythrocyte-delivered photoactivatable oxaliplatin nanoprodrug for enhanced antitumor efficacy and immune response.

ABSTRACT: The outcome of conventional platinum (Pt)-based chemotherapy is limited by reduced circulation, failure to accumulate in the tumor, and dose-limiting toxicity arising from non-controllable activation. To address these limitations, we present an erythrocyte-delivered and near-infrared (NIR) photoactivatable Pt^IV nanoprodrug for advanced cancer treatment. Compared with small molecule Pt^IV prodrugs, this nanoprodrug exhibits significantly enhanced stability, prolonged circulation in the blood, and minimized side effects. The hitchhiking of the nanoprodrug on erythrocytes dramatically increases Pt accumulation in the tumor. Upon irradiation, the nanoprodrug releases oxaliplatin in a controllable manner, resulting in significant antitumor activity against breast tumors in vivo, as evidenced by the complete elimination of tumors from a single-dose injection. Additionally, this nanoprodrug is associated with remarkably enhanced immunopotentiation. Our study highlights an efficient strategy to overcome the shortcomings of traditional Pt-based chemotherapy via the erythrocyte-mediated delivery of an NIR-activatable nanoprodrug of oxaliplatin, a clinically used anticancer drug.

SUBMITTER: Wang N

PROVIDER: S-EPMC8580000 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An erythrocyte-delivered photoactivatable oxaliplatin nanoprodrug for enhanced antitumor efficacy and immune response.

Wang Na N Deng Zhiqin Z Zhu Qi Q Zhao Jianxiong J Xie Kai K Shi Peng P Wang Zhigang Z Chen Xianfeng X Wang Feng F Shi Jiahai J Zhu Guangyu G

Chemical science 20211006 43

The outcome of conventional platinum (Pt)-based chemotherapy is limited by reduced circulation, failure to accumulate in the tumor, and dose-limiting toxicity arising from non-controllable activation. To address these limitations, we present an erythrocyte-delivered and near-infrared (NIR) photoactivatable Pt<sup>IV</sup> nanoprodrug for advanced cancer treatment. Compared with small molecule Pt<sup>IV</sup> prodrugs, this nanoprodrug exhibits significantly enhanced stability, prolonged circulat ...[more]

PMID: 34880985

Similar Datasets

Project description:PurposeDendritic cell (DC)-based cancer vaccines is a newly emerging and potent form of immune therapy. As for any new technology, there are still considerable challenges that need to be addressed. Here, we investigate the antitumor potential of a novel liposomal vaccine, M/CpG-ODN-TRP2-Lipo.MethodsWe developed a vaccination strategy by assembling the DC-targeting mannose and immune adjuvant CpG-ODN on the surface of liposomes, which were loaded with melanoma-specific TRP2180-188 peptide as liposomal vaccine. M/CpG-ODN-TRP2-Lipo treatment was used to intendedly induce activation of DCs and antitumor- specific immune response in vivo.ResultsOur results demonstrated in vitro that the prepared liposomal particles were efficiently taken up by DCs. This uptake led to an enhanced activation of DCs, as measured by the upregulation of MHC II, CD80, and CD86. Furthermore, M/CpG-ODN-TRP2-Lipo effectively inhibited the growth of implanted B16 melanoma and prolonged the survival of mice. This therapy significantly reduced the number of myeloid-derived suppressor cells (MDSCs) and regulatory T cells, while simultaneously increasing the number of activated T cells, tumor antigen-specific CD8+ cytotoxic T cells, and interferon-γ-producing cells. At the same time, it was found to suppress tumor angiogenesis and tumor cell proliferation, as well as up-regulate their apoptosis. Interestingly, MyD88-knockout mice had significantly shorter median survival times compared to wild-type mice following the administration of M/CpG-ODN-TRP2-Lipo.ConclusionsThe results suggested that the antitumor activities of the vaccine partially rely on the Myd88 signaling pathway. Interestingly, compared to whole tumor cell lysate-based vaccine, M/CpG-ODN-TRP2-Lipo, tumor specific antigen peptide-based vaccine, improved survival of tumor-bearing mice as well as enhanced their antitumor responses. All in all, we describe a novel vaccine formulation, M/CpG-ODN-TRP2-Lipo, with the aim of improving antitumor responses by alleviating the immunosuppressive environment in tumors.

Dataset Information

An erythrocyte-delivered photoactivatable oxaliplatin nanoprodrug for enhanced antitumor efficacy and immune response.

Publications

An erythrocyte-delivered photoactivatable oxaliplatin nanoprodrug for enhanced antitumor efficacy and immune response.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets