论文部分内容阅读
Tumor cells develop resistance to chemotherapeutic drugs through multiple mechanisms.Overexpression of efflux transporters is an important source of drug resistance.Efflux transporters such as P-glycoprotein reduce intracellular drug accumulation and compromise drug efficacy.Various nanoparticle-based approaches have been investigated to overcome efflux-mediated resistance.These include the use of formulation excipients that inhibit transporter activity and co-delivery of the anticancer drug with a specific inhibitor of transporter function or expression.However, in recent years, increasing studies have shown breast cancer is initiated and maintained by a small fraction of breast cancer stem cells (BCSCs), which are responsible for metastasis,recurrence and drug resistance.Current chemotherapeutics (such as paclitaxel, doxorubicin or cisplatin) fail to cure breast cancer due to the drug-resistance of BCSCs.After chemotherapy, the residual BCSCs produce tumor bulk though continuous self-renewral and differentiation and many other cancer stem cells have been found in their cancer celllines, such as brain cancer cell (U87),hepatic cancer cell (Hep G-2).Therefore, in order to cure cancer, it is necessary to inhibit self-renewral of CSCs, and eradicate them by improving sensitivity to chemotherapy.Therefore,therapeutic strategies that selectively target CSCs will ultimately lead to better cancer treatments.Currently, accessible conventional therapeutic agents mainly eliminate the bulk tumor but do not eliminate CSCs.Therefore, the discovery and improvement of CSC-targeting therapeutic agents are necessary.So following stretage may be the better method to cure different cancers:(1) Targeting conventional therapeutic agents to cancer cells and cancer stem cells;(2) Targeting delivery conventional therapeutics and CSCs sensitive therapeutics to caner cell and cancer stem cells respectively;(3) The combination of ABC transporter inhibitors (ATIs) and conventional therapeutics with nanocarrier to reverse the MDR of CSCs, and then realize better treatment of cancer disease