Figure 1.

(a) Synthetic scheme of hydrophobic 5β-cholanic acid modified GC. (b) Schematic illustration of effective self-assembly of DOX-CNPs by hydrophobic interactions between DOX and cholanic acid moieties of GC polymers in mild conditions. (c) Synthetic scheme of thiolated glycol chitosan (tGC) by chemical conjugation of Sulfo-LC-SPDP to the amine group of GC polymers. (d) Schematic illustration of fthe ormulation process of small and compact Poly-siRNA/tGC complexes. First, weak charge interactions occur between negatively charged Poly-siRNA and positively charged GC polymers. Next, Poly-siRNA/tGC complexes are further stabilized by chemical disulfide crosslinking between tGC and Poly-siRNA. (e) Schematic representation of the combinational delivery process by GC-based nano-platforms. CNP-based delivery platforms exhibit almost similiar physico-chemical properties after encapsulation of drugs with extremely different physical features, i.e. DOX and siBcl2. Finally DOX-CNPs and siRNA-CNPs show outstanding tumor accumulation and localization tendencies thereafter similar cellular uptake followed by intracellular trafficking to the site of action, cytosol for the RNAi process and nucleus for DOX action, which will benefit anti-cancer therapeutic effects in a combinatorial way.