Sialic acid-functionalized nanomaterials for targeted cancer therapy, diagnosis, and theranostics.

Targeted cancer therapy, by leveraging the overexpression of specific molecules on tumors, such as sialic acid (SA), offers a promising strategy to enhance antitumor efficacy while minimizing off-target effects. SA modification of nanomaterials can target both tumor cells and tumor-associated immune cells, thereby improving drug delivery and therapeutic outcomes. Tumor cells with high SA expression bind to sialic acid-binding immunoglobulin-like lectins (Siglecs) and selectins expressed on tumor-associated immune cells, potentially contributing to immunosuppression. By binding to these receptors, SA-modified nanomaterials enhance tumor biodistribution and cellular uptake, and improve the efficacy of chemotherapeutics. Additionally, SA-functionalized nanomaterials can target tumor-associated immune cells such as tumor-associated macrophages (TAMs), and allow for the delivery of chemoimmunotherapeutic agents that can deplete TAMs or reprogram them to an antitumor M1 phenotype. SA-modified nanomaterials can also target peripheral blood monocytes and neutrophils, and serve as vehicles for drug delivery to the tumor core. Furthermore, SA-functionalized nanomaterials are valuable in cancer imaging and theranostics, enhancing the efficacy of imaging agents and theranostic nanomaterials. Theismultifaceted approach holds significant potential for advancing targeted cancer therapies.