J Gynecol Oncol | Volume 6, Issue 1 | Research Article | Open Access
Huang RC1,4#, Luo YJ1#, Su YH2,3* and Ling CQ1*
1Naval Medical University (Second Military Medical, University), China
2Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, China
3Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, China
4Department of Outpatient, Hangu Traditional Chinese Medicine Hospital in Binhai New Area, China
#These authors contributed equally to this work
*Correspondance to: Yong-Hua Su
Fulltext PDFObjectives: Several Chinese traditional medicines have been used in chemotherapy, with Shikonin receiving significant attention for its effective anti-tumor properties. However, its low solubility and lack of precise targeting in vivo have limited its biological efficacy, hindering its clinical application. This study focuses on the preparation of Shikonin-loaded Dual targeting Nanomicelles (SDN) that leverage antibody-antigen interactions and tumor microenvironment responsiveness. The anti- Human Epidermal growth factor Receptor-2 antibodies (anti-Her-2) attached to the surface of SDN can effectively target Her-2, a protein that is overexpressed in SKBr-3 cells and BT-474 cells. On the other hand, in response to a slightly higher temperature in tumor tissue, SDN can undergo a phase transition, potentially facilitating endocytosis due to increased hydrophobicity. In this study, we investigate the anti-tumor effects of SDN on in vitro and in vivo breast cancer models with high expression of her-2 positive. Methods: To enhance targeted delivery of shikonin to tumor sites, we developed a Nanodrug Delivery System (SDN), characterized it, and used it to treat BT-474 and SKBR-3 cell lines. Cell proliferation was observed through CCK8 experiments. Acute toxicity experiments involved tail vein injections to assess the potential toxic and side effects of SDN on mouse organs, evaluating its safety. The anti-tumor efficacy of SDN was validated using a BT-474 mouse subcutaneous tumor model. Results: SDN exhibited a complete core-shell spherical shape with excellent serum stability. It demonstrated significant inhibition of HER-2-positive cell proliferation. Acute toxicity experiments indicated improved safety of SDN with reduced organ damage. In vivo tumor inhibition experiments revealed that SDN outperformed traditional shikonin in tumor suppression. Conclusion: By developing Shikonin-loaded Dual targeting Nanomicelles (SDN), this study addressed the limitations of traditional shikonin such as poor water solubility and low targeting efficiency. The enhanced anti-tumor efficacy and biosafety of shikonin warrant further investigation.
Shikonin; Nanomicelle; Dual-targeting; Anti-tumor; Safety
Huang RC, Luo YJ, Su YH, Ling CQ. HER-2 and TME Dual Targeting Shikonin-Loaded Nanomicelle for Anti- Breast Cancer Treatment. J Gynecol Oncol. 2024;6(1):1081..