Acta Biomater 2022 Aug 15. Epub 2022 Aug 15.
College of Chemistry and Materials Science, Jinan University, Guangzhou, 510632, P. R. China. Electronic address:
In the complex tumor microenvironment (TME), tumor-associated macrophages (TAMs) play an important role in immunosuppression and tumor growth; hence, tumor cells are no longer the only target during tumor treatment. However, how to simultaneously target both tumor cells and TAMs to effectively eliminate the tumor remains a challenge. Herein, based on the specific receptors for cancer cells and TAMs, we prepared bidirectional anisotropic palladium nanoclusters (
[email protected] NPs) to simultaneously target tumor cells and TAMs for enhancing the therapeutic effect. In these nanoclusters, the Pd-HA part was obtained by modifying hyaluronic acid (HA) on the surface of ultra-small Pd nanozymes that could target CT26 cells. Moreover, with the high peroxidase (POD) and catalase (CAT) activity of Pd nanozymes, Pd-HA NPs directly caused cancer cell death by producing HO and highly toxic reactive oxygen therapy (ROS) through chemodynamic therapy (CDT). The other part of Pd NPs functioned as a carrier that linked mannose (Man) and the imiquimod molecule (R837) to obtain
[email protected] NPs, which could specifically connect the mannose receptor of TAMs and perform targeted reprogramming of TAMs to M1 phenotype to reverse immunosuppression and further activate immunotherapy to form "double therapy". Therefore, the strategy of "double therapy" provides new sights for treating malignant tumors. STATEMENT OF SIGNIFICANCE: : How to simultaneously target tumor cells and tumor-associated macrophages (TAMs) in the tumor microenvironment remains a challenge in tumor therapy. In this study, we used a simple method to construct bidirectional anisotropic Pd nanoclusters (
[email protected] NPs) that can simultaneously target tumor cells and TAMs. With the modified HA, the Pd-HA showed good targeting to CT26 cells under the effect of Pd nanozymes that can directly kill cancer cells through the production of toxic reactive oxygen species. On the other hand, with the targeting of mannose on the surface of nanoclusters,
[email protected] were specifically ingested by TAMs, which induced their transformation into M1 phenotype to reverse tumor immunosuppression. Through bidirectional anisotropy,
[email protected] NPs achieved the "double therapy" effect with CDT and immunotherapy on tumors.