Treating Breast Cancer Metastasis With Cabazitaxel Loaded PCL6500-PEG5000 Polymeric Micelles

At present, breast cancer threat more and more women's health. And the high metastasis is responsible for the high mortality in breast cancer patients. According to the report,over 90% of the patents die of the metastasis of breast cancer, especial metastasize to the lung.Therefor ,reduce cancer cell metastasis is full of meaning for therapy breast cancer. In this reserch , we construct a novel nano-polymeric delivery system to load drug .we hope it can carry drug targetting to primary tumor and metastatic nodules, kill cancer cell for maximization and provent normal body cell from side effect for minimize.First we choose Polycaprolactone(PCL) decorated with Polyethylene glycol (PEG)—PCL6500-PEG5000 as carrier material. Loading drug—cabazitaxel(CTX) by a typical film hydration/sonication method to prepare polymeric micelles(PCM). In vitro, the characterizations of PCM were investigated. Our experiment result exhibit PCM get50.13±11.96 nm of average diameter and -2.03 ± 0.12mV of the zeta potential. Over 97% of the encapsulation efficiency indicate drug can be loaded into system as expect.When PCM was diluted with PBS(pH7.4), the mean diameter was barely changed within 24. Moreover, in PBS(pH7.4 and pH5.0),the encapsulation effeciency won't change as time within 24h. It suggest PCM can stably exist in blood circulatory system and drug won't be lose in advance.With highly metastic breast cancer cell 4T1 cell ,we perform cellular uptake and cell migration assay. Thie experiment result show PCM can be largely uptook into cell,colocalization with Cytoplasm. In CTX of 10 ng/mL, only 9.25% cell can migrate to the other side of the membrane in CTX injection group relative to negtive control group,and PCM can inhibit 93% plus cell migration. These indicate cabazitaxel can dramatically inhibit cancer cell migration.In nu/nu nude mice ,we inject 4T1 cell into the right mammary gland of the mice to induce the orthotopic metastatic breast cancer model. We investigated the therapeutic efficacy of PCM on tumor growth and metastasis and biodistribution in the model. The vivo result show that PCM can targetting accumulate to the tumor site as time,4h come to the highest.compare to saline group,the tumor volume was 35.5 ± 6.2% for CTX injection and and 25.8 ± 5.8% for PCM,respectively,which indecated both CTX and PCM can effective inhibit the growth of breast cancer. In other hand,lung metastasis can also be reduced by CTX injection and PCM, inhibition efficiency was 86% and 93.5% conrespondingly. Noticeable,PCM is better than CTX in two respect.Take all this, cabazitaxel can dramatically inhibit the growth the breast cancer and the metastasis. If cabazitaxel is loaded into PCM ,the inhibtion efficacy can be further promoted. So this work may expand cabazitaxle apply field to breast cancer and provide an encouraging strategy on treating breast cancer metastasis.