Penetrable Nanoplatform for "Cold" Tumor Immune Microenvironment Reeducation.

ABSTRACT

Lack of tumor-infiltration lymphocytes (TILs) and resistances by overexpressed immunosuppressive cells (principally, myeloid-derived suppressor cells (MDSCs)) in tumor milieu are two major challenges hindering the effectiveness of immunotherapy for "immune-cold" tumors. In addition, the natural physical barrier existing in solid cancer also limits deeper delivery of drugs. Here, a tumor-targeting and light-responsive-penetrable nanoplatform (Apt/PDGs/@pMOF) is developed to elicit intratumoral infiltration of cytotoxic T cells (CTLs) and reeducate immunosuppressive microenvironment simultaneously. In particular, porphyrinic metal-organic framework (pMOF)-based photodynamic therapy (PDT) induces tumor immunogenic cell death (ICD) to promote CTLs intratumoral infiltration and hot "immune-cold" tumor. Upon being triggered by PDT, the nearly 10 nm adsorbed drug-loaded dendrimer de-shields from the nanoplatform and spreads into the deeper tumor, eliminating MDSCs and reversing immunosuppression, eventually reinforcing immune response. Meanwhile, the designed nanoplatform also has a systemic MDSC inhibition effect and moderate improvement of overall antitumor immune responses, resulting in effective suppression of distal tumors within less significant immune-related adverse effects (irAEs) induced.