Nanomedicine Penetration to Tumor: Challenges, and Advanced Strategies to Tackle This Issue

SIMPLE SUMMARY: Scientists have been working on the development of nanomedicine-based tumor therapy, rather than conventional treatment, to treat cancer for several years. Unfortunately, biological barriers hinder the delivery of nanomedicine to tumors. There are different strategies applied by researchers to improve the nanomedicine penetration to tumors, such as the modification of nanoparticle features and controlling the cancer micro-environment. However, complicated cancer micro-environments and delivery problems prevent these approaches from achieving optimal results. Changes in the extra-cellular matrix or blood vessels modify tumor microenvironments in a way that provides improved nanomedicine penetration and distribution but not to an optimal level. Herein, we reviewed the challenges of nanomedicine penetration to tumors along with possible approaches to deal with this concern. ABSTRACT: Nanomedicine has been under investigation for several years to improve the efficiency of chemotherapeutics, having minimal pharmacological effects clinically. Ineffective tumor penetration is mediated by tumor environments, including limited vascular system, rising cancer cells, higher interstitial pressure, and extra-cellular matrix, among other things. Thus far, numerous methods to increase nanomedicine access to tumors have been described, including the manipulation of tumor micro-environments and the improvement of nanomedicine characteristics; however, such outdated approaches still have shortcomings. Multi-functional convertible nanocarriers have recently been developed as an innovative nanomedicine generation with excellent tumor infiltration abilities, such as tumor-penetrating peptide-mediated transcellular transport. The developments and limitations of nanomedicines, as well as expectations for better outcomes of tumor penetration, are discussed in this review.