Mediation of synergistic chemotherapy and gene therapy via nanoparticles based on chitosan and ionic polysaccharides

Nanoparticles (NPs)-based on various ionic polysaccharides, including chitosan, hyaluronic acid, and alginate have been frequently summarized for controlled release applications, however, most of the published reviews, to our knowledge, focused on the delivery of a single therapeutic agent. A comprehensive summarization of the co-delivery of multiple therapeutic agents by the ionic polysaccharides-based NPs, especially on the optimization of the polysaccharide structure for overcoming various extracellular and intracellular barriers toward maximized synergistic effects, to our knowledge, has been rarely explored so far. For this purpose, the strategies used for overcoming various extracellular and intracellular barriers in vivo were introduced first to provide guidance for the rational design of ionic polysaccharides-based NPs with desired features, including long-term circulation, enhanced cellular internalization, controllable drug/gene release, endosomal escape and improved nucleus localization. Next, four preparation strategies were summarized including three physical methods of polyelectrolyte complexation, ionic crosslinking, and self-assembly and a chemical conjugation approach. The challenges and future trends of this rapidly developing field were finally discussed in the concluding remarks. The important guidelines on the rational design of ionic polysaccharides-based NPs for maximized synergistic efficiency drawn in this review will promote the future generation and clinical translation of polysaccharides-based NPs for cancer therapy.