An EPR-Independent extravasation Strategy: Deformable leukocytes as vehicles for improved solid tumor therapy

Effective delivery of therapeutic modality throughout the tumorous nidus plays a crucial role in successful solid tumor treatment. However, conventional nanomedicines based on enhanced permeability and retention (EPR) effect have yielded limited delivery/therapeutic efficiency, due mainly to the heterogeneity of the solid tumor. Leukocytes, which could intrinsically migrate across the vessel wall and crawl through tissue interstitium in a self-deformable manner, have currently emerged as an alternative drug delivery vehicle. In this review, we start with the intrinsic properties of leukocytes (e.g., extravasation and crawling inside tumor), focusing on unveiling the conceptual rationality of leveraging leukocytes as EPR-independent delivery vehicles. Then we discussed various cargoes-loading/unloading strategies for leukocyte-based vehicles as well as their promising applications. This review aims to serve as an up-to-date compilation, which might provide inspiration for scientists in the field of drug delivery.