Glycans as Targets for Drug Delivery in Cancer

SIMPLE SUMMARY: Alterations in glycosylation are frequently observed in cancer cells. Different strategies have been proposed to increase drug delivery to the tumor site in order to improve the therapeutic efficacy of anti-cancer drugs and avoid collateral cytotoxicity. The exploitation of drug delivery approaches directed to cancer-associated glycans has the potential to pave the way for better and more efficient personalized treatment practices. Such strategies taking advantage of aberrant cell surface glycosylation patterns enhance the targeting efficiency and optimize the delivery of clinically used drugs to cancer cells, with major potential for the clinical applications. ABSTRACT: Innovative strategies have been proposed to increase drug delivery to the tumor site and avoid cytotoxicity, improving the therapeutic efficacy of well-established anti-cancer drugs. Alterations in normal glycosylation processes are frequently observed in cancer cells and the resulting cell surface aberrant glycans can be used as direct molecular targets for drug delivery. In the present review, we address the development of strategies, such as monoclonal antibodies, antibody–drug conjugates and nanoparticles that specific and selectively target cancer-associated glycans in tumor cells. The use of nanoparticles for drug delivery encompasses novel applications in cancer therapy, including vaccines encapsulated in synthetic nanoparticles and specific nanoparticles that target glycoproteins or glycan-binding proteins. Here, we highlight their potential to enhance targeting approaches and to optimize the delivery of clinically approved drugs to the tumor microenvironment, paving the way for improved personalized treatment approaches with major potential importance for the pharmaceutical and clinical sectors.