Lymph node-targeted immune-activation mediated by imiquimod-loaded mesoporous polydopamine based-nanocarriers

Area of Science:

• Immunology
• Nanotechnology
• Biomaterials

Background:

• Toll-like receptor (TLR) agonists stimulate the innate immune system for anticancer immunotherapy.
• Current TLR agonists cause "wasted inflammation" due to rapid dissemination, limiting efficacy and increasing side effects.
• Restricting TLR agonist action to lymphoid tissues is crucial for improving anticancer immunotherapy.

Purpose of the Study:

• To develop novel nano-adjuvants for enhanced anticancer immunotherapy.
• To improve the delivery and retention of imiquimod (a TLR 7 agonist) in lymphoid tissues.
• To combine photothermal therapy with immune activation for melanoma treatment.

Main Methods:

• Imiquimod (R837) was loaded into mesoporous polydopamine (MPDA) nanocarriers.
• The nanocarrier surface was modified with polyvinyl pyrrolidone (PVP) to improve lymphatic drainage.
• The nano-adjuvants' ability to promote dendritic cell (DC) maturation and their transport to lymph nodes (LNs) were evaluated.
• The combination of photothermal effect and immune activation was assessed for melanoma treatment.

Main Results:

• The designed PVP-MPDA@R837 nano-adjuvants efficiently loaded imiquimod.
• These nano-adjuvants enhanced DC maturation compared to free imiquimod.
• The nanocarriers showed improved transport and retention in proximal lymph nodes.
• Effective DC activation and CD8+ T cell responses were observed in draining LNs.
• MPDA-based photothermal effect induced tumor apoptosis, enhancing immune responses.
• Significant inhibition of subcutaneous B16 melanoma growth was achieved.

Conclusions:

• The developed PVP-MPDA@R837 nano-adjuvants effectively deliver TLR 7 agonists to lymph nodes.
• This strategy enhances immune activation and anticancer efficacy.
• Combining photothermal therapy with lymphatic-focused immune activation offers a promising approach for melanoma treatment.