Breast cancer has been the first killer of women health worldwide for decades, and metastasis is the leading cause of death for breast cancer patients.

Recently, the chemo-immunotherapy combination strategy has attracted much attention in cancer therapy field. However, the existence of cancer stem cells (CSC) is always neglected, which might cause the failure of chemo-immunotherapy, because CSC are often tolerant to T cells, and the proportion of CSC in tumor tissues is too low to be cleaned up by systemically administrated chemotherapeutic agents.

Regarding this issue, Prof. LI Yaping's group from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, constructed a cocktail strategy based on a spatio-temporally controlled nano device, named PM@THL, into which chemotherapy against both bulk tumor cells and CSC and immune checkpoint blockade therapy are integrated. The research was published in Advanced Materials.

In this study, the chemotherapeutic agent paclitaxel, the anti-CSC agent thioridazine, and the PD-1/PD-L1 inhibitor HY19991 were all incorporated into an enzyme/pH dual-sensitive nanoparticle with a micelle-liposome double-layer structure.

PM@THL is a hybrid liposome with the size of about 100 nm in blood circulation and not easily cleared by mononuclear-phagocyte system, endowing it with good pharmacokinetics stability. When transferring to tumor tissues, the liposome dissociated to micelles with the size of 40-50 nm, favoring cellular uptake by tumor cells and achieving sequential drug release at the set time and site.

The therapy effect was tested on metastatic breast cancer mice model. PM@THL increased the intra-tumoral drug concentrations, reduced the tumor volumes by 93.45%, and inhibited 97.64% of the lung metastasis nodules formation. It also declined the proportion of CSC and enhances the T cells infiltration in tumor tissues, thus prolonged the survival of mice. Therefore, the scientist concluded that this cocktail nano device could be a promising strategy for improving the therapy of metastatic breast cancer.

This work was supported by National Natural Science Foundation of China, Key Scientific Research Program of CAS, and the Youth Innovation Promotion Association of CAS.

The article link: https://doi.org/10.1002/adma.201806202

Cocktail strategy based on spatio-temporally controlled nano device for treating metastatic breast cancer. (Image by Lang Tianqun)

Contacts:
Prof. LI Yaping,
E-mail: ypli@simm.ac.cn

(Credit: YIN Qi; Editor: PAN Peihua)