Abstract

Polysaccharides possess great potential as building blocks in the development of drug delivery vehicles. This can be attributed to their outstanding virtues, such as biocompatibility,biodegradability, and possession of a plenty of functional groups. Their chemical flexibility
allows for the modification of polysaccharides, leading to diverse functionalities that are valuable in biomedical applications. A promising functionality is stimuli-responsiveness that results in a change of physical or chemical properties of polysaccharide-based nanocarriers in
response to an environmental change, such as pH, temperature, and light. Herein, recent strategies to develop polysaccharide-based nanomaterials for biomedical application are mapped out. Furthermore, using carboxymethyl cellulose (CMC) as a promising pH-sensitive
polysaccharide, two types of stimuli-responsive polysaccharide-based nanomaterials were developed and evaluated as potential tumor targeting drug delivery nanocarriers.
The first system involves dual pH/reduction responsive polysaccharide-based bionanogels(ssBNGs) prepared by aqueous crosslinking polymerization. CMC is grafted with pendant
oligo(ethylene oxide) containing methacrylate (OEOMA), and crosslinked with a disulfidelabeled dimethacrylate, yielding disulfide crosslinked ssBNGs with a diameter ≈ 24 nm
measured by dynamic light scattering. ssBNGs exhibit dual pH/reduction-responsive drug release, attributed to less interactions between the encapsulated drug molecules and CMC at acidic pH and the reductive cleavage of disulfide crosslinkers. The possibility of conjugating a
targeting ligand to ssBNGs is confirmed with a model water-soluble UV-active dye.
The second system includes dual pH/temperature responsive bionanogels (DuR-BNGs). Thermoresponsive polymers undergo volume change above their lower critical solution temperature (LCST) due to a hydrophilic/hydrophobic transition. DuR-BNGs were prepared by grafting thermoresponsive monomers: di(ethylene oxide) methyl ether methacrylate (MEO2MA) and OEOMA from CMC in the presence of crosslinker via aqueous crosslinking polymerization. The self-association of grafted P(MEO2MA-co-OEOMA) above their LCST resulted in a micelle-like structure of DuR-BNGs as well as narrow size distribution. DuR-BNGs exhibit pH responsive drug release due to the pH-dependent interaction of CMC with drug molecules. The
temperature-responsive drug release was driven by the shrinkage of DuR-BNGs networks upon high temperature treatment, thereby expelling encapsulated cargoes causing rapid drug release. The non-specific protein absorption of DuR-BNGs is evaluated with bovine serum albumin
(BSA) as a model.
The potential application of two types of dual stimuli-responsive bionanogels (BNGs) in drug delivery is demonstrated with cell viability by MTT assay and cellular uptake using confocal laser scanning microscopy and flow cytometry.