Light-triggered multifunctional nanoplatform for efficient cancer photo-immunotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Cancer immunotherapy faces challenges from tumor immune escape and adverse effects.
• Photo-immunotherapy, combining phototherapy (PDT/PTT) with immunotherapy, enhances treatment efficacy.
• Novel nanoparticle systems are needed to improve drug delivery and therapeutic synergy.

Purpose of the Study:

• To develop and evaluate mesoporous hexagonal core-shell zinc porphyrin-silica nanoparticles (MPSNs) for advanced photo-immunotherapy.
• To assess MPSNs as a drug carrier and photosensitizer for synergistic cancer treatment.
• To investigate the efficacy of MPSNs-based photo-immunotherapy combined with checkpoint blockade against primary and metastatic tumors.

Main Methods:

• Synthesis and characterization of MPSNs with zinc porphyrin core and mesoporous silica shell.
• Loading MPSNs with R837 (imiquimod) for pH-responsive drug release and combining with programmed death ligand-1 (PD-L1) checkpoint blockade.
• Evaluating laser-triggered photodynamic therapy (PDT) and photothermal therapy (PTT) activity of MPSNs@R837.
• Assessing the induction of immunogenic cell death, dendritic cell maturation, and tumor-specific immune responses in vivo.
• Investigating the therapeutic effects on primary and metastatic tumors and systemic toxicity.

Main Results:

• MPSNs demonstrated high laser-triggered PDT and PTT activity and excellent drug loading capacity.
• MPSNs@R837 induced efficient immunogenic cell death and promoted dendritic cell maturation via pH-responsive R837 release.
• The combined therapy of MPSNs@R837, PDT, PTT, and PD-L1 blockade significantly inhibited primary and metastatic tumors.
• The treatment exhibited negligible systemic toxicity.

Conclusions:

• MPSNs serve as effective photosensitizers and drug carriers for synergistic photo-immunotherapy.
• The developed therapeutic strategy integrating PTT, PDT, and checkpoint blockade shows significant potential for suppressing cancer metastasis.
• This approach offers a promising avenue for more effective and safer cancer treatment.