Drug-initiated poly(thiocitc acid) polymer incorporating host-guest interaction for cancer combination chemotherapy

Summary: Combination chemotherapy has shown considerable promise for cancer therapy. However, the hydrophobicity of chemotherapeutic agents and the difficulties of precise drug co-administration severely hinder the development of combination chemotherapy. Herein, we develop a polymeric drug delivery system (D-PTA-CD) to provide robust loading capacity, glutathione-responsive drug release, and precise combination therapy. The vehicle is prepared based on poly(thioctic acid) (PTA) polymers using DM1, a chemotherapeutic agent, as the initiator to endow the vehicle with cancer-inhibiting activity. β-cyclodextrins are incorporated into the side chains to enhance drug loading capacity via host-guest interactions. Attributing to the sufficient disulfide bond on the backbone, D-PTA-CD exhibits accelerated drug release triggered by elevated glutathione levels. Doxorubicin (DOX) and camptothecin (CPT) are encapsulated by D-PTA-CD to afford the combination chemotherapy nanoparticles (NP), DOX-NP, and CPT-NP, respectively, which exhibit significant synergetic anti-cancer effects, highlighting the enormous potential of D-PTA-CD as a versatile drug delivery platform for cancer combination chemotherapy.