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

Kai Yang; Bing Bai; Feihe Huang; Guocan Yu

doi:10.1016/j.isci.2024.109070

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

iScience. 2024 Feb 1;27(3):109070. doi: 10.1016/j.isci.2024.109070. eCollection 2024 Mar 15.

Authors

Kai Yang^{1

2

3}, Bing Bai³, Feihe Huang^{1

2}, Guocan Yu³

Affiliations

¹ Stoddart Institute of Molecular Science, Department of Chemistry, Zhejiang University, Hangzhou 310027, P.R. China.
² ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 311215, P.R. China.
³ Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, P.R. China.

Abstract

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.

Keywords: Cancer; Cell biology; Drug delivery system; Polymer chemistry.