Self-assembled Pt(II) metallacycles enable precise cancer combination chemotherapy

Significance Coadministration of drug molecules in adequate combinations for cancer treatment reduces the doses of each constituent, overcomes resistance mechanisms, and reduces the influence of tumor heterogeneity. Here we utilize coordination-driven self-assembly to prepare platinum(II) metallacycles comprising two drug molecules with distinct anticancer mechanisms in precise ratios. Nanoformulations fabricated by encapsulating the metallacycles into amphiphilic diblock copolymers efficiently enter cancer cells and release the active drug molecules at the exact loading ratio in the reductive cancer microenvironments, leading to a synergistic anticancer effect and therefore a favorable treatment outcome. This study provides a promising supramolecular methodology for the precise organization and delivery of bioactive molecules for inducing synergistic biological effects that maximize therapeutic efficacy.