Petaloid Metal-Organic Frameworks for Resiquimod Delivery To Potentiate Antitumor Immunity.

ABSTRACT

The morphological features of materials significantly influence their interactions with cells, consequently affecting the cellular uptake of these materials. In this study, we examine the cellular uptake behavior of spherical metal-organic frameworks (MOFs) and petaloid MOFs, both possessing similar sizes and compositions. In comparison to spherical MOFs, dendritic cells (DCs) and macrophages exhibit superior phagocytic uptake of petaloid MOFs. Next, the results demonstrate that R848@petaloid MOFs more effectively promote the repolarization of tumor-associated macrophages (TAMs) from the M2 to M1 phenotype and the maturation of DCs. More importantly, the R848-loaded petaloid MOFs are found to significantly enhance the therapeutic effects of radiotherapy (RT) by eliciting antitumor responses. Furthermore, R848@petaloid MOFs combined with RT and αPD-L1 elicit a potent abscopal effect, effectively suppressing tumor metastasis. Therefore, this work proposes a new strategy to enhance the uptake of immunomodulators by immune cells through modulating the morphology of drug delivery carriers.