Ly6Chi Monocytes Delivering pH‐Sensitive Micelle Loading Paclitaxel Improve Targeting Therapy of Metastatic Breast Cancer

Many immune cells are capable of homing to sites of disease and eradicating infections and abnormal cells. However, their efficacy is usually down‐regulated in tumor microenvironments and it is difficult to boost. It is presumed that the anticancer activity of immune cells can be improved by integrating an additional therapeutic modality such as chemotherapy into the cells. Here, Ly6Chi monocytes armed with the paclitaxel (PTX)‐loading pH‐sensitive micelle (PM), termed as PM@MC, are prepared. The PM internalization does not significantly affect the properties of the host Ly6Chi monocytes. In the 4T1 metastatic breast cancer mice model, PM@MCs home to both primary tumor and the lung metastasis foci. PM@MC exhibit 15‐fold higher intratumor PTX accumulation than the commercial PTX injection, and achieve a tumor inhibiting rate of 96.8% and a lung metastasis suppression rate of 99.2%. No significant change is recorded in histology of major organs and in hematological and biochemical parameters after PM@MC treatment. The pH‐sensitive micelle/Ly6Chi monocyte drug delivery device thus has the application potential in the targeting therapy of breast cancer with metastasis. Paclitaxel (PTX)‐loading pH‐responsive micelle (PM)‐loading Ly6Chi circulating monocytes (PM@MC) are constructed. PM@MC can be efficiently internalized by 4T1 cells, increasing the PTX amount in tumors and in the lungs. Considering that tumor‐targeting behavior of PM@MC is independent of enhanced permeability and retention effect and heterogeneity of tumors, this can be an effective strategy for targeting therapy for metastatic breast cancer.