Penetrable Nanoplatform for "Cold" Tumor Immune Microenvironment Reeducation

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Immunotherapy

Background:

• Immunotherapy faces challenges in
• immune-cold
• tumors due to lack of tumor-infiltrating lymphocytes (TILs) and immunosuppressive cells like myeloid-derived suppressor cells (MDSCs).
• Solid tumors also present physical barriers limiting drug delivery.

Purpose of the Study:

• To develop a tumor-targeting, light-responsive nanoplatform to enhance immunotherapy effectiveness.
• To simultaneously promote cytotoxic T cell (CTL) infiltration and reeducate the immunosuppressive tumor microenvironment.

Main Methods:

• A nanoplatform (Apt/PDGs_^s@pMOF) combining aptamers, drug-loaded dendrimers, and porphyrinic metal-organic frameworks (pMOFs) was designed.
• Photodynamic therapy (PDT) triggered drug release and immunogenic cell death (ICD).
• Systemic effects on MDSCs and immune responses were evaluated.

Main Results:

• The nanoplatform induced ICD, promoting CTL infiltration and converting
• immune-cold
• tumors to an immune-hot state.
• PDT triggered drug release, which penetrated deeper into the tumor to eliminate MDSCs and reverse immunosuppression.
• The nanoplatform demonstrated systemic MDSC inhibition and suppressed distal tumors with reduced immune-related adverse effects (irAEs).

Conclusions:

• The developed nanoplatform effectively overcomes key immunotherapy resistance mechanisms in solid tumors.
• This approach holds promise for enhancing cancer immunotherapy by modulating the tumor microenvironment and improving drug delivery.