The treatment of hepatocellular carcinoma with SP94 modified asymmetrical bilayer lipid-encapsulated Cu(DDC) 2 nanoparticles facilitating Cu accumulation in the tumor.

Background: Copper diethyldithiocarbamate (Cu(DDC) ₂ ) has been demonstrated to possess excellent antitumor activity. However, the extremely poor water solubility of Cu(DDC) ₂ bring difficulty for its formulation research. In this study, we aim to develop a novel nanocarrier for Cu(DDC) ₂ delivery to overcome this obstacle and enhance antitumor activity.
Methods: The SP94 modified asymmetrical bilayer lipid-encapsulated Cu(DDC) ₂ nanoparticles (DCDP) was established by combining the method of inverse microemulsion aggregation and thin-film dispersion. In vitro cellular assays and in vivo 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 ₅₀ , 200 nM). And DCDP effectively inhibited tumor growth with a high tumor inhibition rate of 74.84%. Furthermore, Cu(DDC) ₂ 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) ₂ .