Activating Antitumor Immunity and Antimetastatic Effect Through Polydopamine-Encapsulated Core-Shell Upconversion...

Area of Science:

• Oncology
• Nanomedicine
• Immunotherapy

Background:

• Cancer metastasis causes most deaths, yet current therapies often focus only on primary tumors.
• Combining photodynamic therapy (PDT) and photothermal therapy (PTT) offers synergistic potential for cancer treatment.
• Existing PDT/PTT strategies primarily target primary tumors, overlooking metastatic disease.

Purpose of the Study:

• To develop and evaluate a synergistic phototherapy approach using upconversion-polymer hybrid nanoparticles for enhanced primary tumor elimination and metastasis control.
• To investigate the immunomodulatory effects of this combined PDT/PTT strategy.
• To assess the efficacy of this nanoplatform in combination with immune checkpoint blockade for inhibiting tumor relapse and metastasis.

Main Methods:

• Fabrication of upconversion-polymer hybrid nanoparticles loaded with chlorin e6 photosensitizer.
• In vitro and in vivo evaluation of combined photodynamic and photothermal therapy efficacy.
• Assessment of systemic and humoral antitumor immune responses.
• Combination therapy with immune checkpoint blockades in tumor metastasis models.

Main Results:

• The hybrid nanoparticles effectively generated reactive oxygen species upon near-infrared light irradiation, enabling synergistic PDT/PTT.
• The synergistic phototherapy significantly enhanced primary tumor elimination and induced robust systemic antitumor immunity.
• Combination therapy with immune checkpoint blockades suppressed tumor relapse and metastasis, significantly prolonging survival in mouse models.

Conclusions:

• Synergistic phototherapy using upconversion-polymer hybrid nanoparticles is a potent strategy for primary tumor eradication and combating metastasis.
• This nanoplatform effectively enhances immunogenic cell death and boosts antitumor immune responses.
• The approach holds promise for developing novel immunotherapeutic strategies against metastatic cancer.