Tumor immunotherapy boosted by R837 nanocrystals through combining chemotherapy and mild hyperthermia

Area of Science:

• Oncology
• Immunology
• Materials Science

Background:

• Melanoma is an aggressive skin cancer with poor prognosis, often resistant to immunotherapy due to low immune cell infiltration.
• Current immunotherapies for melanoma show limited efficacy and are often combined with chemotherapy or radiotherapy.
• Developing combined therapeutic strategies that enhance immune response and prevent metastasis is crucial for melanoma treatment.

Purpose of the Study:

• To develop a novel drug delivery system for melanoma treatment that combines immunomodulation, induction of immunogenic cell death (ICD), and immune enhancement.
• To investigate the efficacy of the developed system in enhancing cytotoxic T cell (CTL) infiltration and inhibiting melanoma growth, metastasis, and recurrence.

Main Methods:

• Preparation of imiquimod (R837) nanocrystals coated with polydopamine (PDA) to form R837@PDA.
• Loading of R837@PDA into chitosan hydrogel (CGP) to create the R837@PDA@CGP (RPC) drug-loaded gel system.
• Evaluation of RPC's effects on inducing ICD, enhancing CTL infiltration, and inhibiting melanoma progression in vivo.

Main Results:

• The RPC system successfully induced immunogenic cell death (ICD) in melanoma cells.
• Significant enhancement in cytotoxic T cell (CTL) infiltration within the melanoma tumor microenvironment was observed.
• RPC treatment effectively inhibited melanoma tumor growth, metastasis, and recurrence, acting as an in situ vaccine.

Conclusions:

• The developed R837@PDA@CGP system demonstrates significant potential as a combined therapeutic strategy for melanoma.
• This approach effectively leverages immunomodulation and ICD induction to boost anti-tumor immunity and overcome treatment resistance.
• The system holds promise for long-term inhibition of melanoma metastasis and recurrence by establishing a robust cancer-immunity cycle.