Radiotherapy Potentiates the P-Selectin Targeted Cancer Drug Delivery Based on a Cisplatin and Mitoxantrone Coassembled Fucoidan Nanogel
Huimin Wang, Hong Deng, Menghan Gao, Yiyi Zhang, Runmeng Liu, Wei Hou, Haiyan Xu, Weiqi Zhang
Abstract
Targeted delivery of coencapsulated drugs can increase therapeutic indices of cancers including improved tumor inhibition and safety profile. However, most cancers lack tumor specific receptors (antigens) to guide the targeted delivery. Tumoral P-selectin can be rapidly upregulated after ionization radiation, indicating it is a highly selective target for drug delivery. In this work, we had fucoidan, a natural polysaccharide with intrinsic affinity toward P-selectin, and the chemotherapeutics cisplatin and mitoxantrone coassembled into a composite nanogel (FCM), and meanwhile exploited its P-selectin targeted therapeutic potentials in combination with radiotherapy using a murine breast cancer model. The radiation significantly enhanced the P-selectin level in tumor and subsequently boosted the cancer-targeted delivery of FCM. In current FCM, fucoidan not only acted as matrix for drugs encapsulation but also functioned as targeting ligand, thus providing a facile and P-selectin targeted codelivery of chemotherapeutics that could be potentiated by tumor radiation.