Affiliation:
1. MOE Key Laboratory of High Performance Polymer Materials and Technology and Department of Polymer Science & Engineering College of Chemistry & Chemical Engineering Nanjing University Nanjing 210023 P. R. China
2. Department of Radiation Oncology School of Medicine Stanford University Stanford CA 94305 USA
Abstract
AbstractTumor vascular disrupting therapy has offered promising opportunities to treat cancer in clinical practice, whereas the overall therapeutic efficacy is notably limited due to the off‐target effects and repeated dose toxicity of vascular disrupting agents (VDAs). To tackle this problem, a VDA‐free biomimetic semiconducting polymer nanoparticle (SPNP) is herein reported for precise tumor vascular disruption through two‐stage light manipulation. SPNP consists of a semiconducting polymer nanoparticle as the photothermal agent camouflaged with platelet membranes that specifically target disrupted vasculature. Upon the first photoirradiation, SPNP administered in vivo generates mild hyperthermia to trigger tumor vascular hemorrhage, which activates the coagulation cascade and recruits more SPNP to injured blood vessels. Such enhanced tumor vascular targeting of photothermal agents enables intense hyperthermia to destroy the tumor vasculature during the second photoirradiation, leading to complete tumor eradication and efficient metastasis inhibition. Intriguingly, the mechanism study reveals that this vascular disruption strategy alleviates splenomegaly and reverses the immunosuppressive tumor microenvironment by reducing myeloid‐derived suppressor cells. Therefore, this study not only illustrates a light‐driven self‐recruitment strategy to enhance tumor vascular disruption via a single dose of biomimetic therapeutics but also deciphers the immunotherapeutic role of vascular disruption therapy that is conducive to clinical studies.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Jiangsu Province
State Key Laboratory of Analytical Chemistry for Life Science
Fundamental Research Funds for the Central Universities
Subject
Mechanical Engineering,Mechanics of Materials,General Materials Science
Cited by
9 articles.
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