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

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.

• Authors: Zhiguo Gao , Yaojia Li , Yu Zhang , Peijing An , Fanghui Chen , Jian Chen , Chaoqun You , Zhifei Wang , Baiwang Sun
• Journal: Nanoscale (Nanoscale) Vol. 12 Issue 15 Pg. 8139-8146 (Apr 21 2020) ISSN: 2040-3372 [Electronic] England
• PMID: 32236229 (Publication Type: Journal Article)

Chemical References

• Drug Carriers
• Hyaluronan Receptors
• Porphyrins
• tetracarboxyphenylporphine
• Samarium
• Copper
• Hyaluronic Acid
• Disulfiram

Topics

• Animals
• Cell Line, Tumor
• Copper (administration & dosage, chemistry)
• Disulfiram (administration & dosage)
• Drug Carriers
• Drug Delivery Systems
• Female
• Humans
• Hyaluronan Receptors (metabolism)
• Hyaluronic Acid (chemistry, metabolism)
• Mice
• Nanostructures (administration & dosage, chemistry)
• Porphyrins (chemistry)
• Samarium (chemistry)
• Triple Negative Breast Neoplasms (drug therapy, metabolism, pathology)
• Xenograft Model Antitumor Assays