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

Abstract

Toll-like receptor (TLR) agonists are the potent stimulants of innate immune system and hold promises as an adjuvant for anticancer immunotherapy. Unfortunately, most of them are limited by a prompt dissemination, and thus caused "wasted inflammation". Hence, how to restrict their action radius into lymphoid tissues is of great relevance to enhance their efficacy and concomitantly alleviates the side effects. Here, imiquimod (R837), a TLR 7 agonist, was loaded into mesoporous polydopamine (MPDA) nanocarriers with high efficiency. Moreover, its surface was modified by polyvinyl pyrrolidone (PVP) to enhance their lymphatic drainage ability. These nano-adjuvants have obvious advantages in promoting dendritic cell (DC) maturation in comparison to free R837. Moreover, their transportation and retention ability in proximal lymph nodes (LNs) were also confirmed, by which lymphatic drug exposure can be maximized to a great extent. Consequently, effective DC activation and CD8⁺ T cell responses were observed as expected by R837 released in draining LNs. This effect was further enhanced by the presence of endogenous tumor antigens from apoptosis debris induced by MPDA-based photothermal effect, and thus led to the growth inhibition of subcutaneous B16 melanomas. The results demonstrated the great potency against melanoma of the designed PVP-MPDA@R837 nano-adjuvants by combining photothermal conversion property of MPDA with lymphatic-focused immune-activation.

Keywords: Drug delivery; Imiquimod; Immunotherapy; Lymph nodes; Mesoporous polydopamine.