Biological rationale for the design of polymeric anti-cancer nanomedicines

Understanding the biological features of cancer is the basis for designing efficient anti-cancer nanomedicines. On one hand, important therapeutic targets for anti-cancer nanomedicines need to be identified based on cancer biology, to address the unmet medical needs. On the other hand, the unique pathophysiological properties of cancer affect the delivery and interactions of anti-cancer nanomedicines with their therapeutic targets. This review discusses several critical cancer biological properties that challenge the currently available anti-cancer treatments, including cancer heterogeneity and cancer stem cells, the complexcity of tumor microenvironment, and the inevitable cancer metastases. In addition, the biological bases of the enhanced permeability and retention (EPR) effect and tumor-specific active targeting, as well as the physiological barriers for passive and active targeting of anti-cancer nanomedicines are covered in this review. Correspondingly, possible nanomedicine strategies to target cancer heterogeneity, cancer stem cells and metastases, to overcome the challenges related to tumor passive targeting and tumor penetration, and to improve the interactions of therapeutic payloads with the therapeutic targets are discussed. The focus is mainly on the designs of polymeric anti-cancer nanomedicines.