Mannose and Mannose‐6‐Phosphate Receptor–Targeted Drug Delivery Systems and Their Application in Cancer Therapy

In order to overcome the main disadvantages of conventional cancer therapies, which prove to be inadequate because of their lack of selectivity, the development of targeted delivery systems is one of the main focuses in anticancer research. It is repeatedly shown that decorating the surface of nanocarriers with high-affinity targeting ligands, such as peptides or small molecules, is an effective way to selectively deliver therapeutics by enhancing their specific cellular uptake via the binding between a specific receptor and the nanosystems. Nowadays, the need of finding new potential biological targets with a high endocytic efficiency as well as a low tendency to mutate is urgent and, in this context, mannose and mannose-6-phosphate receptors appear promising to target anticancer drugs to cells where their expression is upregulated. Moreover, they open the path to encouraging applications in immune-based and gene therapies as well as in theragnostic purposes. In this work, the potential of mannose- and mannose-6-phosphate-targeted delivery systems in cancer therapy is discussed, emphasizing their broad application both in direct treatments against cancer cells with conventional chemotherapeutics or by gene therapy and also their encouraging capabilities in immunotherapy and diagnostics purposes.