A multicomponent-based microemulsion for boosting ovarian cancer therapy through dual modification with transferrin and
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ORIGINAL ARTICLE
A multicomponent-based microemulsion for boosting ovarian cancer therapy through dual modification with transferrin and SA-R6H4 Haijun Zhao 1 & Mengyuan Chen 1 & Zhujiang Zhao 2 & Linjia Zhu 3 & Shaofei Yuan 3 Accepted: 17 September 2020 # Controlled Release Society 2020
Abstract Balancing the antitumor activity and systemic toxicity of tripterine still faces a big challenge due to the narrow therapeutic window. To address this issue, we report a microemulsion system based on tripterine, brucea oil, and glycyrrhizin, and dual modified with both transferrin and cell-penetrating peptide SA-R6H4 (Tf/SA-R6H4-TBG-MEs) for combinational and tumortargeted cancer therapy. Such a microemulsion exhibited a spherical shape with a size of ~50 nm and a mildly-negative charge. The half-maximal inhibitory concentration (IC50) of Tf/SA-R6H4-TBG-MEs against ovarian cancer SKOV3 cells was 0.27 ± 0.43 μg tripterine/mL, which was 5.85 times lower than that of free tripterine. The cellular uptake of tripterine after treatment with Tf/SA-R6H4-TBG-MEs was 1.56 times higher than that of TBG-MEs (non-modified microemulsion). In pharmacokinetics studies, the area under the curve of Tf/SA-R6H4-TBG-MEs increased by 1.97 times compared with that of the physical mixture group. The tumoral accumulation of tripterine was significantly improved in Tf/SA-R6H4-TBG-MEs group than TBG-MEstreated group. In antitumor efficacy in vivo, Tf/SA-R6H4-TBG-MEs exhibited the strongest inhibition of tumor growth and the longest survival period among all the groups, which is associated with the rational combination, microemulsion system, and dual modification with tumor-targeted ligands. Importantly, Tf/SA-R6H4-TBG-MEs significantly reduced the toxicity of tripterine against the liver and kidney. Our design provides a new approach for efficient and safe ovarian cancer therapy based on a multicomponent combination. Keywords Combinational therapy . Tripterine . Brucea oil . Targeted drug delivery . SA-R6H4 cell-penetrating peptide . Ovarian cancer
Introduction Ovarian cancer, a common gynecological tumor with high mortality and recurrence rate, seriously threatens women’s health
* Zhujiang Zhao [email protected] * Shaofei Yuan [email protected] 1
Department of Obstetrics and Gynecology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, People’s Republic of China
2
Department of Medical Genetics and Developmental Biology, Medical School of Southeast University, Nanjing 210009, People’s Republic of China
3
Department of Medical Oncology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325200, People’s Republic of China
worldwide [1, 2]. According to the latest survey, the incidence of ovarian cancer reaches about 9 ~ 14/100,000 in the Western countries, such as Europe and the USA; even in the lower area, such as China and Japan, the incidence is also up to 6.1/ 100,000, resulting in a soaring to the top of gynecological malignancies in recent years [3, 4]. In addition to traditional che
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