Taking advantage of the highly permeable vasculature and lack of lymphatic drainage in solid tumors (EPR effect), nanosized drug delivery systems or nanomedicines have been extensively explored for tumor-targeted drug delivery. However, in most clinical cases tumors such as the early stage tumors and post-surgery microscopic residual tumors have not yet developed such pathological EPR features, i.e., EPR-deficient. Therefore, nanomedicines may not be applicable for such these tumors. Macrophages by nature can actively home and extravasate through the tight vascular wall into tumors and migrate to their hypoxic regions, and possess perfect stealth ability for long blood circulation and impressive phagocytosis for drug loadings. Thus, nanomedicines loaded in macrophages would harness both merits and gain the active tumor homing capability independent of the EPR effect for treatments of the EPR-deficient tumors. Herein, the critical considerations, current progress, challenges and future prospects of macrophages as carriers for nanomedicines are summarized, aiming at rational design of EPR-independent tumor-targeting active nanomedicines for targeted early and adjuvant cancer chemotherapy.
Keywords: EPR effect; cancer drug delivery; cell carriers; macrophage; nanomedicine; tumor targeting.
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