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

ABSTRACT

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 (IC₅₀, 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.

KEYWORDS:

• Disulfiram
• asymmetrical bilayer lipid shell
• cu(DDC)₂ solid core nanoparticles
• SP94
• hepatocellular carcinoma
• copper ion

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17425247.2023.2155631

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [82172086], National Key R&D Program of China [2020YFE0201700], Liaoning Revitalization Talents Program [XLYC1907111, XLYC1908031], Liaoning Province Doctoral Start-up Fund Program [2019-BS-226], Liaoning BaiQianWan Talents Program [(2020)78], Shenyang Science and Technology Talent Support Program [RC210447], the Career Development Program for Young and Middle-aged Teachers of Shenyang Pharmaceutical University [ZQN2019004] and ‘Dual Service’ Program of University in Shenyang.