Introductions: Ovarian cancer is a stubborn malignancy of gynecological system with a high mortality rate. Docetaxel (DTX), the second-generation of anti-tumor drug Taxane, has shown superior efficacy over classic paclitaxel (PTX) in certain cancers. However, its clinical application is hindered by poor bioavailability. The natural spice extract curcumin (Cur) has been discovered to improve the bioavailability of DTX. Therefore, it is meaningful to develop a combined drug strategy of DTX and Cur with methoxy poly (ethylene glycol)poly (L-lactic acid) (MPEG-PLA) copolymers in ovarian cancer therapy. Methods: Injectable DTX-Cur/M nanomicelles were synthesized and characterized in the study. The molecular interactions between DTX, Cur and copolymer were simulated and the drug release behavior was investigated. The anti-tumor activity and anti-tumor mechanisms of DTX-Cur/M were evaluated and explored in both cells and mice model of xenograft human ovarian cancer. Results: DTX-Cur/M nanomicelles with an average particle size of 37.63 nm were obtained. The drug release experiment showed sustained drug release from DTX-Cur/M nanomicelles. The MTT assay and apoptotic study indicated that DTX-Cur/M exhibited stronger inhibition and pro-apoptotic effects on A2780 cells compared with DTX or Cur alone. In vivo antitumor experiment results confirmed that the DTX-Cur/M played the most effective role in anti-ovarian cancer therapy by inhibiting tumor proliferation, suppressing tumor angiogenesis and promoting tumor apoptosis. Conclusion: We designed injectable DTX-Cur/M nanomicelles for co-delivery of DTX and Cur agents to the tumor site through systemic administration. The DTX-Cur/M nanomicelle would be a biodegradable, sustainable and powerful anti-tumor drug candidate with great potential in ovarian cancer treatment.

Two of the biggest hurdles in the deployment of chemotherapeutics against glioma is a poor drug concentration at the tumor site and serious side effects to normal tissues. Nanocarriers delivering different drugs are considered to be one of the most promising alternatives. In this study, a dual delivery system (methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL)) loaded with α-mangostin (α-m) and doxorubicin (Dox) was decorated and constructed by self-assembly to determine its ability to treat glioma. Molecular dynamics simulations showed that MPEG-PCL could provide ideal interaction positions for both α-m and Dox, indicating that the two drugs could be loaded into MPEG-PCL. Based on the in vitro results, MPEG-PCL loaded with α-m and Dox (α-m-Dox/M) with a size of 25.68 nm and a potential of −1.51 mV was demonstrated to significantly inhibit the growth and promote apoptosis in Gl261, C6 and U87 cells, and the effects of the combination were better than each compound alone. The mechanisms involved in the suppression of glioma cell growth were blockage of the cell cycle in S phase by inhibition of CDK2/cyclin E1 and promotion of apoptosis through the Bcl-2/Bax pathway. The synergetic effects of α-m-Dox/M effectively inhibited tumor growth and prolonged survival time without toxicity in mouse glioma models by inducing glioma apoptosis, inhibiting glioma proliferation and limiting tumor angiogenesis. In conclusion, a codelivery system was synthesized to deliver α-m and Dox to the glioma, thereby suppressing the development of glioma by the mechanisms of cell cycle arrest and cellular apoptosis, which demonstrated the potential of this system to improve the chemotherapy response of glioma.

Acquired chemoresistance presents a major clinical impediment, which is an urgent problem to be solved. Interestingly, myeloma cell leukemia‐1 (MCL‐1) and folate receptor expression levels are higher in chemotherapy‐resistant patients than in pretreatment patients. In this study, a multifunctional folic acid (FA)‐targeting core–shell structure is presented for simultaneous delivery of shMCL‐1 and paclitaxel (PTX). The transfection efficiency of shMCL‐1 with the FA‐targeting delivery system is higher than with a nontargeting delivery system in Skov3 and A2780T cells. The FA‐targeting system significantly inhibits cell growth, blocks cell cycles, and promotes apoptosis of cancer cells in vitro. The mechanisms involved in inhibiting growth are related to Bcl‐2/Bax and cdc2/Cyclin B1 pathways. An analysis of RNA sequencing suggests that shMCL‐1 reverses chemoresistance through regulating genes such as regulator of chromosome condensation 2 (RCC2). The synergetic effect of shMCL‐1 and PTX effectively inhibits tumor growth in both PTX‐resistant and normal cancer models by inducing tumor apoptosis, inhibiting proliferation, and limiting tumor angiogenesis. The study results indicate that a FA‐targeting delivery system combining shMCL‐1 with PTX can simultaneously target tumor sites and restore the sensitivity of chemotherapy‐resistant cancer to PTX. These findings have important implications for patients with normal or PTX‐resistant cancer.

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