期刊
NANOSCALE
卷 13, 期 19, 页码 8998-9008出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0nr08024a
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资金
- Science and Technology Development Plan Projects of Jilin Province [20200201558JC]
- Special Project of Health Research Talents in Jilin Province [2019SC2062]
- Health Technology Innovation Project of Jilin Province [2019J028]
Combination therapy using PD-L1 blockade, PD-L1 siRNA, and DOX shows great potential for treating prostate cancer bone metastasis through synergistic chemoimmunotherapy. Stem cell membrane-camouflaged nanoparticles can enhance blood retention and tumor accumulation, improving therapeutic efficacy.
Programmed cell death ligand 1 (PD-L1) blockade has achieved great success in cancer immunotherapy. PD-L1 siRNA can restore the immune anti-tumor activity of T cells by downregulating the level of PD-L1 on tumor cells, but the efficiency of PD-1/PD-L1 monotherapy is relatively low. Doxorubicin (DOX) can induce tumor cell apoptosis, and then increase the release of tumor antigen. But the expression of PD-L1 in tumor tissues treated with DOX will be enhanced adaptively. Therefore, DOX combination with PD-L1 siRNA can produce a good synergistic anti-tumor effect. In this study, stem cell membrane (SCM) camouflaged polydopamine nanoparticles carrying DOX and PD-L1 siRNA (PDA-DOX/siPD-L1@SCM) were constructed for targeting prostate cancer (PCa) bone metastases. PDA-DOX/siPD-L1@SCM NPs could effectively enhance blood retention and improve accumulation at tumor sites. In vitro and in vivo studies demonstrated that PDA-DOX/siPD-L1@SCM NPs showed excellent performance in synergistic chemoimmunotherapy for PCa bone metastases. Hence, this study provided an effective strategy for developing biomimetic multifunctional nanoparticles for PCa bone metastasis treatment.
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