Doxorubicin and siRNA-PD-L1 co-delivery with T7 modified ROS-sensitive nanoparticles for tumor chemoimmunotherapy

Area of Science:

• Nanomedicine
• Immunotherapy
• Cancer Biology

Background:

• Tumor cells evade immune responses by overexpressing immunosuppressive molecules like PD-L1, which inhibits T-cell activity.
• Targeting the PD-1/PD-L1 pathway is a key strategy in cancer immunotherapy.
• Chemotherapy drugs like doxorubicin can be limited by delivery and resistance mechanisms.

Purpose of the Study:

• To develop a novel nanoparticle system for co-delivery of siRNA-PD-L1 and doxorubicin.
• To enhance tumor targeting and cellular uptake via T7 peptide modification.
• To investigate the synergistic effects of chemoimmunotherapy in a tumor model.

Main Methods:

• Fabrication of ROS-responsive nanoparticles modified with T7 peptide for co-delivery of siRNA-PD-L1 and doxorubicin.
• In vitro assessment of T7-mediated cellular uptake and ROS-triggered drug release.
• In vivo evaluation of tumor targeting, chemoimmunotherapy efficacy, and antitumor effects in a 4T1 tumor model.

Main Results:

• Nanoparticles demonstrated efficient T7-mediated cellular uptake and intracellular ROS-triggered payload release in vitro.
• In vivo studies showed improved tumor targeting and enhanced chemoimmunotherapy in the 4T1 model.
• Co-delivery system significantly outperformed doxorubicin-only nanoparticles by promoting T-cell proliferation via siRNA-PD-L1.

Conclusions:

• ROS-responsive nanoparticles offer a promising platform for combined siRNA-PD-L1 immunotherapy and doxorubicin chemotherapy.
• The T7 peptide facilitates targeted delivery to tumor cells.
• This dual-delivery strategy effectively overcomes tumor-induced immunosuppression and enhances therapeutic outcomes.