Journal
BIOMATERIALS
Volume 270, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.120690
Keywords
Immunogenic cell death; Nanoscale coordination polymer; PD-L1; Point-source burst; Tumor
Funding
- National Cancer Institute [1R01CA223184, 1R01CA216436]
- University of Chicago Medicine Comprehensive Cancer Center [NIH CCSG: P30 CA014599]
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This study presents a novel core-shell nanoscale coordination polymer particle design for tri-modality cancer therapy, which efficiently suppresses cancer growth and metastasis through reactivating immune responses.
Cancer immunotherapy, particularly the inhibition of immune checkpoints with neutralizing antibodies, has revolutionized the treatment of some cancer patients. However, immune checkpoint blockade has not provided survival benefits to most patients with colorectal and ovarian cancers. This work reports the design of acid sensitive core-shell nanoscale coordination polymer particles (NCP) comprising a carboplatin prodrug and an siRNA against PD-L1 (siPD-L1) in the core and digitoxin on the shell for tri-modality cancer therapy. Upon cellular uptake, NCP particles rapidly burst in acidic organelles to release carboplatin for apoptosis, digitoxin for inducing immunogenicity, and siPD-L1 for PD-L1 knockdown. With long blood circulation and high tumor accumulation, NCP particles efficiently suppress the growth and metastasis of syngeneic cancers through reactivating innate and adaptive immune responses. NCP particles thus provide a promising platform to synergistically combine chemotherapy and immunotherapy for the treatment of advanced and aggressive cancers.
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