A CD44-targeted Cu(<scp>ii</scp>) delivery 2D nanoplatform for sensitized disulfiram chemotherapy to triple-negative breast cancer
Zhiguo Gao, Yao‐Jia Li, Yu Zhang, Peijing An, Fanghui Chen, Jian Chen, Chaoqun You, Zhifei Wang, Bai‐Wang Sun
Abstract
Recent studies have suggested that the anticancer activity of disulfiram (DSF, an FDA-approved alcohol-abuse drug) is Cu-dependent. Low system toxicity and explicit pharmacokinetic characteristics of DSF necessitate safe and effective Cu supplementation in local lesion for further applications. Herein, we presented a new conceptual 'nanosized coordination transport' strategy of Cu(ii) that was realized in porphyrin-based metal-organic frameworks, Sm-TCPP, with strong binding ability to Cu(ii) due to their coordination interactions. Sm-TCPP(Cu) was coated by hyaluronic acid (HA) that termed by Sm-TCPP(Cu)@HA, acting as 'beneficial horse' to target the tumor-localized HA receptor (CD44), thus liberating Cu(ii) ions in cellular overexpressed reductants. The CD44-mediated Cu(ii) accumulation efficiency of Sm-TCPP(Cu)@HA was benchmarked in vitro and vivo against the free TCPP (Cu) via ICP-MS analysis. More importantly, the sensitization effects of Sm-TCPP(Cu)@HA on the anticancer activity of DSF were demonstrated in vivo and in vitro. This study offered a new class of targeted Cu supplements to sensitize DSF for the effective treatment of cancer and established a versatile methodology for constructing a safe and specific delivery of metal ions within living organisms.