Bioinspired Polymeric Nanomedicines with Tumor Extracellular Matrix Anchoring Capability for Prolonged Tumor Retention and Drug Delivery.

The unsatisfactory delivery efficacy of nanocarriers adversely restricts the therapeutic activity of encapsulated cargoes, and the current strategies, such as ligand decoration, is limited by the tumor heterogeneity of patients. Inspired by the excellent adhesion behavior of mussels, we developed a nanocarrier (Ac-NP) of catechol-decorated hyperbranched polyglycerol (HPG) to enable strong anchoring to ECM components (collagen I, laminin, proteoglycans), markedly improving the delivery efficacy of various anticancer agents. Meanwhile, to minimize its nonspecific ECM anchoring following intravenous injection, the nanocarrier was masked by 4-carboxyphenylboronic acid (PBA), and the resultant TAc-NPs exhibited specific tumor extracellular ECM-anchoring capability. TAc-NPs showed a 2.3-fold increase in tumor accumulation, with over 70% retained in the ECM. This ECM-anchored system significantly enhanced the therapeutic efficacy of extracellular (BB94), intracellular (doxorubicin), and membrane-targeted (BMS-1) drugs for efficient chemoimmunotherapy. Our strategy offers a broadly applicable nanoplatform for delivery of various types of anticancer agents without the limitation of tumor heterogeneity.