Nanoparticles Functionalized with Ligands of Cell Surface Nucleolin for Cancer Therapy and Diagnosis

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Conventional cancer chemotherapies are often limited by their non-targeted nature and their inadequate delivery to the tumor affecting the normal tissues and leading to toxic adverse effects. In order to improve the anticancer efficacy and safety of these drugs, as well as the diagnosis capacity of imaging agents, nanoparticles drug delivery system has been developed combining ligands enabling tumor targeting at a cellular level and drug carrier capacity. Nucleolin (NCL) is a multifunctional protein that could shuttle from nucleolus to nucleoplasm, cytoplasm and cell surface. This ribonucleo protein over expressed at the cell surface of cancer cells is involved in many cancer processes supporting tumorigenesis such as cell proliferation and apoptosis. Additionally, NCL expression is enhanced in angiogenic vessels, enabling multi-targeting strategies toward the tumor microenvironment. In this context, several compounds targeting NCL, such as the aptamer AS1411, the peptide F3 and the multivalent pseudopeptide N6L, have been developed and investigated for cancer therapy. Due to their cancer cell targeting capacities, these compounds have been evaluated to mediate highly specific and effective nanoparticles for drug delivery to the tumor. In this report, we present a review of literature focusing on drug-loaded nanoparticles conjugated with these nucleolin ligands, strikingly emphasizing the success of such a strategy.