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A CD44-targeted Cu(ii) delivery 2D nanoplatform for sensitized disulfiram chemotherapy to triple-negative breast cancer

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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.

Graphical abstract: A CD44-targeted Cu(ii) delivery 2D nanoplatform for sensitized disulfiram chemotherapy to triple-negative breast cancer

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Supplementary files

Article information


Submitted
15 Jan 2020
Accepted
12 Mar 2020
First published
13 Mar 2020

Nanoscale, 2020, Advance Article
Article type
Communication

A CD44-targeted Cu(II) delivery 2D nanoplatform for sensitized disulfiram chemotherapy to triple-negative breast cancer

Z. Gao, Y. Li, Y. Zhang, P. An, F. Chen, J. Chen, C. You, Z. Wang and B. Sun, Nanoscale, 2020, Advance Article , DOI: 10.1039/D0NR00434K

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