Bioresponsive and multifunctional cyclodextrin-based non-viral nanocomplexes in cancer therapy: Building foundations for gene and drug delivery, immunotherapy and bioimaging

The interest towards application of nanomaterials in field of cancer therapy is that the drawbacks of conventional therapies including chemoresistance, radio-resistance and lack of specific targeting of tumor cells can be solved by nanotechnology. Cyclodextrins (CDs) are amphiphilic cyclic oligosaccharides that can be present in three forms of α-, β- and γ-CDs, and they can be synthesized from natural sources. The application of CDs in cancer shows an increasing trend due to benefits of these nanocomplexes in improving solubility and bioavailability of current bioactives and therapeutics for cancer. CDs are widely utilized in delivery of drugs and genes in cancer therapy, and by targeted delivery of these therapeutics into target site, they improve anti-proliferative and anti-cancer potential. The blood circulation time and tumor site accumulation of therapeutics can be improved using CD-based nanostructures. More importantly, the stimuli-responsive types of CDs including pH-, redox- and light-sensitive types can accelerate release of bioactive compound at tumor site. Interestingly, the CDs are able to mediate photothermal and photodynamic impact in impairing tumorigenesis in cancer, enhancing cell death and improving response to chemotherapy. In improving the targeting ability of CDs, their surface functionalization with ligands has been conducted. Moreover, CDs can be modified with green products such as chitosan and fucoidan, and they can be embedded in green-based nanostructures to suppress tumorigenesis. The internalization of CDs into tumor cells can occur through endocytosis and this can be clethrin-, caveolae- or receptor-mediated endocytosis. Furthermore, CDs are promising candidates in bioimaging, cancer cell and organelle imaging as well as isolating tumor cells. The main benefits of using CDs in cancer therapy including sustained and low release of drugs and genes, targeted delivery, bioresponsive release of cargo, ease of surface functionalization and complexation with other nanostructures. The application of CDs in overcoming drug resistance requires more investigation.