Novel mitochondrial targeting charge-reversal polysaccharide hybrid shell/core nanoparticles for prolonged systemic circulation and antitumor drug delivery.

Novel mitochondrial targeting charge-reversal polysaccharide hybrid shell/core nanoparticles for prolonged systemic circulation and antitumor drug delivery. Drug Deliv. 2019 Dec;26(1):1125-1139 Authors: Fang L, Zhang W, Wang Z, Fan X, Cheng Z, Hou X, Chen D Abstract Stability in systemic circulation, effective tumor accumulation, and the subsequent crucial subcellular targeting are significant elements that maximize the therapeutic efficacy of a drug. Accordingly, novel nanoparticles based on polysaccharides that simultaneously presented prolonged systemic circulation and mitochondrial-targeted drug release were synthesized. First, the mitochondrial-targeted polymer, 3,4-dihydroxyphenyl propionic acid-chitosan oligosaccharide-dithiodipropionic acid-berberine (DHPA-CDB), was synthesized, which was used to form self-assembled curcumin (Cur)-encapsulated cationic micelles (DHPA-CDB/Cur). Negatively charged oligomeric hyaluronic acid-3-carboxyphenylboronic acid (oHA-PBA), a ligand to sialic acid and CD44, was further added to the surface of the preformed DHPA-CDB/Cur core to shield the positive charges and to prolong blood persistence. oHA-PBA@DHPA-CDB/Cur formed a covalent polyplex of oHA-PBA and DHPA-CDB/Cur via the pH-responsive borate ester bond between PBA and DHPA. The mildly acidic tumor environment led to the degradation of borate ester bonds, thereby realizing the exposure of the cationic micelles and causing a charge reversal f...
Source: Drug Delivery - Category: Drugs & Pharmacology Tags: Drug Deliv Source Type: research