Co-Delivery of Paclitaxel and Interleukin-12 Regulating Tumor Microenvironment for Cancer Immunochemotherapy

Abstract

In the treatment of malignant tumors, the combination of chemotherapy that can directly kill tumor cells and immunotherapy that can activate the body's immune system and regulate tumor microenvironments is becoming one of the most promising cancer treatments. However, to co-deliver agents with different physicochemical properties for immunochemotherapy is still facing a challenge. Here, nanoparticles are developed for the co-delivery of the hydrophobic chemotherapeutic drug paclitaxel (PTX) and biomacromolecule interleukin-12 (IL-12) through the acid-sensitive material mPEG-Dlink_m -PDLLA and low-temperature expansion effect of Pluronic F127. The nanoparticles encrich in the tumor site, significantly inhibit the growth and metastasis of breast cancer cells 4T1, and prolong the overall survival of tumor-bearing mice. The underlying immune mechanism is further explored. The combination of PTX and IL-12 activates T lymphocytes and NK cells to release IFN-γ, selectively inhibits regulatory T cells and induces M1-type differentiation of tumor-related macrophages, thereby improving tumor immunosuppressive microenvironments. This study may provide an effective strategy for cancer immunochemotherapy through co-delivery of chemotherapeutic drug and immune cytokine by the facile thermo-sponge nanoparticles.

Keywords: drug co-delivery; immunochemotherapy; interleukin-12; paclitaxel; tumor microenvironments.