Journal
JOURNAL OF CONTROLLED RELEASE
Volume 308, Issue -, Pages 29-43Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2019.06.031
Keywords
Photothermal-immunotherapy; Gold/platinum nanosystem; PD-L1 blockage; Active tumor targeting; On-demand release
Funding
- National Natural Science Fund for Distinguished Young Scholar [NSFC31525009]
- National Natural Science Funds [NSFC31600811, NSFC31771096, NSFC 31871008]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars, Sichuan Province, China
- Application Fundamental Research Foundation of Sichuan Province Science and Technology Department, China [2016JY0157]
- Sichuan Innovative Research Team Program for Young Scientists [2016TD0004]
- China Postdoctoral Science Foundation [2018M643486, 2018M643484]
- 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University
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Because of the tumor heterogeneity, poor therapeutic outcome is obtained while the conventional treatments, such as surgery, radiotherapy, or chemotherapy are utilized alone. Herein, combinational therapy strategies have been introduced to solve this problem. Photothermal therapy (PTT) as a non-invasive thermal therapeutic manner has attracting enormous attentions not only for the effective inhibition in primary tumors, but also for producing tumor-associated antigens from ablated tumor cell residues which exhibit the feasibility to enhance the therapeutic outcome of immunotherapy. Here, we report the construction and application of Au@Pt-based nanosystem with rationally designed peptide (LyP-1-PLGVRG-(D)PPA-1, (LMP)-P-D) conjugation for cancer photothermal-immunotherapy. The obtained Au@Pt-(LMP)-P-D nanosystem can serve as a matrix metalloproteinase (MMP) activated tumor targeting agents for effective photothermal therapy together with immune checkpoint blockade immunotherapy by the on-demand release of a D-peptide antagonist of programmed cell death-ligand 1 (PD-L1). The PA imaging demonstrates its effective accumulation in the tumor region by the activated tumor targeting moiety derived from the (LMP)-P-D. Moreover, in vivo anti-tumor studies reveal that Au@Pt-(LMP)-P-D nanosystem can effectively eliminate primary tumors via PTT, and further stimulate the activation of cytotoxic T lymphocytes by PD-L1 immune checkpoint blockage, result in inhibiting the growth of distal tumors and alleviating tumor metastasis. The present study provides a promising strategy for the combination treatment of advanced cancer and obtains a valuable therapeutic outcome in tumor photothermal-immunotherapy.
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