Camptothecin Nanowires Remold Tumor-Associated Macrophages Polarization Through the cGAS-STING Signaling-Mediated Antitumor Immunity

This study successfully developed a novel tumor-associated macrophages (TAMs)-targeting nanoplatform-sialic acid-disulfide bond-camptothecin (SA-SS-CPT) nanowires. This system significantly improved the solubility and bioavailability of camptothecin (CPT) and achieved active targeted drug delivery by utilizing sialic acid as a targeting ligand to specifically recognize the highly expressed Siglec-E receptor on TAMs. Upon internalization into TAMs, the disulfide bond in the SA-SS-CPT nanowires was cleaved in response to intracellular glutathione (GSH), leading to the controlled re-lease of CPT. SA-SS-CPT induced DNA damage in TAMs, thereby activating the cGAS-STING signaling pathway, promoting the polarization of TAMs toward the M1 phenotype, enhancing pro-inflammatory and anti-tumor immune responses, and effec-tively inhibiting tumor immune escape. Furthermore, the SA-SS-CPT nanowires syner-gistically enhanced the efficacy of PD-L1 blockade immunotherapy, collectively remod-eling the tumor immune microenvironment and ultimately facilitating significant tumor clearance.