Polysaccharide-based nanocarriers for efficient transvascular drug delivery

Polysaccharide-based nanocarriers (PBNs) are the focus of extensive investigation because of their biocompatibility, low cost, wide availability, and chemical versatility, which allow a wide range of anticancer agents to be loaded within the nanocarriers. Similar to other nanocarriers, most PBNs are designed to extravasate out of tumor vessels, depending on the enhanced permeability and retention (EPR) effect. However, the EPR effect is compromised in some tumors due to the heterogeneity of tumor structures. Transvascular transport efficacy is decreased by complex blood vessels and condensed tumor stroma. The limited extravasation impedes efficient drug delivery into tumor parenchyma, and thus affects the subsequent tumor accumulation, which hinders the therapeutic effect of PBNs. Therefore, overcoming the biological barriers that restrict extravasation from tumor vessels is of great importance in PBN design. Many strategies have been developed to enhance the EPR effect that involve nanocarrier property regulation and tumor structure remodeling. Moreover, some researchers have proposed active transcytosis pathways that are complementary to the paracellular EPR effect to increase the transvascular extravasation efficiency of PBNs. In this review, we summarize the recent advances in the design of PBNs with enhanced transvascular transport to enable optimization of PBNs in the extravasation of the drug delivery process. We also discuss the obstacles and challenges that need to be addressed to clarify the transendothemial mechanism of PBNs and the potential interactions between extravasation and other drug delivery steps.