Background: Copper diethyldithiocarbamate (Cu(DDC)) has been demonstrated to possess excellent antitumor activity. However, the extremely poor water solubility of Cu(DDC) bring difficulty for its formulation research. In this study, we aim to develop a novel nanocarrier for Cu(DDC) delivery to overcome this obstacle and enhance antitumor activity.

Methods: The SP94 modified asymmetrical bilayer lipid-encapsulated Cu(DDC) nanoparticles (DCDP) was established by combining the method of inverse microemulsion aggregation and thin-film dispersion. cellular assays and tumor-xenograft experiments were conducted to evaluate the tumor chemotherapeutic effect of DCDP. And the vital role of copper ions played in DSF or DDC (DSF/DDC)-based cancer chemotherapy was also explored.

Results: DCDP with an encapsulation efficiency (EE%) of 74.0% were successfully prepared. SP94 modification facilitated cellular intake for DCDP, and promoted apoptosis to repress tumor cell proliferation (IC, 200 nM). And DCDP effectively inhibited tumor growth with a high tumor inhibition rate of 74.84%. Furthermore, Cu(DDC) was found to facilitate the copper ion accumulation in tumor tissues, which is beneficial to therapy with high potency.

Conclusion: DCDP exhibited high-efficient tumor chemotherapeutic efficacy and provided a novel strategy for investigating the anticancer mechanism of Cu(DDC).

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http://dx.doi.org/10.1080/17425247.2023.2155631DOI Listing

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