Dual blockade immune checkpoint for breast cancer treatment based on a tumor penetrating peptide assembling nanoparticle.
Cancer immunotherapy can enhance the antitumor effect of drugs through a combinatorial approach in a synergistic manner. However, the effective targeted delivery of various drugs remains a challenge. We generated a peptide assembling tumor targeted nano delivery system based on a breast cancer homing and penetrating peptide for the co delivery of a programmed cell death ligand 1 (PD L1) small interfering RNA (siRNA)(siPD L1) and an idoleamine 2,3 dioxygenase inhibitor as a dual blockade of an immune checkpoint .The vector is capable of specifically accumulating in the breast cancer tumor site in a way that allows the siRNA to escape from endosomal vesicles after being endocytosed by tumor cells. The drug within these cells then acts to block tryptophan metabolism. The results showed that locally released siPD L1 and 1MT favor the survival and activation of cytotoxic T lymphocytes(CTLs) resulting in apoptosis of breast cancer cells. Therefore, this study provides a potential approach for treating breast cancer by blocking immunological checkpoints through the assembly of micelles with functional peptides.
ACS applied materials interfaces