Point-source burst of coordination polymer nanoparticles for tri-modality cancer therapy

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.