Construction Of Stimuli-responsive Nano-drug Carriers For Drug Delivery

Biodegradable polymeric micelles in aqueous solutions have been extensively explored as amost promising candidate in drug delivery systems for targeted cancer chemotherapy.They can be prepared by the partial hydrophobic modifications of hydrophilic polymers that result in amphiphilic character and consequently induce the self-assembly of polymers into nanoparticles.To overcome severe side effect that are associated with traditional hydrophobic antitumor drugs,nanocarriers used to transport drugs need to overcome many obstacles,including good water solubility,long in vivo circulation times,efficient bioavailability,high preferential accumulation at the tumor sites and low systemic side effects.Specially,stimuli-responsive micelles were furnished for specific tumor targetability and maximal drug release controllability inside the target cells upon changes in physical and chemical environments,such as redox and pH.Therefore,we prepared stimuli-responsive nanoparticles for drug delivery:1)A pH and reduced response polymer nanomicelle drug carrier was designed and prepared.We prepared a copolymer(Mal7-S-S-AcDex)capable of disintegrating in a weak acid and a reducing medium,which the maltoheptaose composed of a glucose ring as a hydrophilic skeleton,and the acetalized glucan as a hydrophobic skeleton.Cystamine with a disulfide bond links the hydrophobic and hydrophilic moieties to form an amphiphilic polymer,spontaneously forms micelles in a PBS buffer solution,and embeds the antitumor drug DOX.The micelles are able to disintegrate in the microenvironment of the tumor cells,releasing the drug and killing the cancer cells.2)The pH and H2O2 double-reactive amphiphilic polymer NM-Mal7-AcMal7 with maltose heptasaccharide as skeleton is prepared.The maltoheptaose skeleton is rich in hydroxyl groups to facilitate modification of nitrogen mustard prodrug molecules,and can be sensitized to the pH of the maltoheptaose molecule by the aldehyde reaction to form AcMal7 as a hydrophobic fragment.The amphiphilic block copolymer can spontaneously form prodrug micelles,and Lapa is embedded in the core to aggregate nanoparticles that promote drug co-delivery.The weak acid environment in the lysosome can disrupt the acetal bond,disintegrate the nanoparticles and release the ROS-responsive nitrogen mustard prodrug and Lapa.Lapa releases H2O2 under the catalysis of biological enzymes,and the nitrogen mustard prodrug molecules are decomposed to form quinone methides and boric acid,which induce tumor cell apoptosis.