Recent advances in pH/enzyme-responsive polysaccharide-small-molecule drug conjugates as nanotherapeutics

Now-a-days, the polysaccharides are extensively employed for the delivery of small-molecule drugs ascribed to their excellent biocompatibility, biodegradability and modifiability. An array of drug molecules is often chem-ically conjugated with different polysaccharides to augment their bio-performances. As compared to their therapeutic precursors, these conjugates could typically demonstrate an improved intrinsic solubility, stability, bioavailability and pharmacokinetic profiles of the drugs. In current years, various stimuli-responsive particu-larly pH and enzyme-sensitive linkers or pendants are also exploited to integrate the drug molecules into the polysaccharide backbone. The resulting conjugates could experience a rapid molecular conformational change upon exposure to the microenvironmental pH and enzyme changes of the diseased states, triggering the release of the bioactive cargos at the targeted sites and eventually minimize the systemic side effects. Herein, the recent advances in pH and enzyme-responsive polysaccharide-drug conjugates and their therapeutic benefits are sys-tematically reviewed, following a brief description on the conjugation chemistry of the polysaccharides and drug molecules. The challenges and future perspectives of these conjugates are also precisely discussed.

Automated summary

Nowadays, polysaccharides are extensively used for drug delivery due to their excellent biocompatibility, biodegradability, and modifiability. Different drug molecules are often chemically conjugated with polysaccharides to improve their solubility, stability, bioavailability, and pharmacokinetic profiles. Stimuli-responsive linkers or pendants, particularly pH and enzyme-sensitive ones, are also employed to integrate drug molecules into polysaccharide backbones. This review systematically discusses recent advances in pH and enzyme-responsive polysaccharide-drug conjugates and their therapeutic benefits, as well as the challenges and future perspectives.