Enhancing Triple Negative Breast Cancer Immunotherapy by ICG-Templated Self-Assembly of Paclitaxel Nanoparticles

Combination cancer immunotherapy has shown promising potential for simultaneously eliciting antitumor immunity and modulating the immunosuppressive tumor microenvironment (ITM). However, combination immunotherapy with multiple regimens suffers from the varied chemo-physical properties and inconsistent pharmacokinetic profiles of the different therapeutics. To achieve tumor-specific codelivery of the immune modulators, an indocyanine green (ICG)-templated self-assembly strategy for preparing dual drug-loaded two-in-one nanomedicine is reported. ICG-templated self-assembly of paclitaxel (PTX) nanoparticles (ISPN), and the application of ISPN for combination immunotherapy of the triple negative breast cancer (TNBC) are demonstrated. The ISPN show satisfied colloidal stability and high efficacy for tumor-specific codelivery of ICG and PTX through the enhanced tumor permeability and retention effect. Upon laser irradiation, the ICG component of ISPN highly efficiently induces immunogenic cell death of the tumor cells via activating antitumor immune response through photodynamic therapy. Meanwhile, PTX delivered by ISPN suppresses the regulatory T lymphocytes (T-regs) to combat ITM. The combination treatment of TNBC with ISPN and alpha PD-L1-medaited immune checkpoint blockade therapy displays a synergistic effect on tumor regression, metastasis inhibition, and recurrence prevention. Overall, the ICG-templated nanomedicine may represent a robust nanoplatform for combination immunotherapy.