The Synthesis And Characterization Of A Novel PH-redox Sensitive Nano-drug Carrier

Cancer is a major human disease. In contrast to conventional therapies-surgery, radiation, and chemotherapy, which have some disadvantages such as the poor selectivity, great side effects, drug resistance and low bioavailability. In the paper, we attempt to design a smart pH-redox sensitive nano drug carrier in the attachment and delivery of water-insoluble anticancer drugs. One goal is the design of pH-reduction sensitive linkage that has novel functional and dynamic properties that are desirable to release water insoluble anticancer drug in a controlled and sustainable way, thus improved the bioavailability of drugsFirstly, graphene oxide (NGO) was synthesized by oxidezing graphite using a modified Hummers’method. The structure and morphology of as-made NGO were characterized by Fourier transform infrared (FTIR), UV-Vis, SEM, TEM and AFM. The NGO prepared with a morphology of lamellar layer contained the oxygen-based functional groups such as-OH,-COOH and C=O. The maximum UV-vis absorption spectrum of NGO was225nm, which showed the successful synthesis of NGO. The average particle size of NGO and NGO-PEG were184.08nm and96.72nm. However, the prepared NGO was soluble in water but aggregated in solutions rich in salts or proteins such as cell medium and serum. This was likely due to screening of the electrostatic charges and nonspecific binding of proteins on the NGO. To our best knowledge, NGO exhibited excellent stability in all biological solutions when appropriately functionalized.Secondly, to impart aqueous stability and prevent biofouling of NGO, we conjugated NGOod biocompatibility of four-armed PEG-amine to the carboxylic acid groups on NGO via carbodiimide catalyzed amide formation. PEGylation was confirmed by Fourier transform infrared (FTIR), UV-vis, size distribution and fluorescence spectra. The resulting PEGylated NGO was further explored in PBS and DMEM solution. NGO-PEG were96.72nm in average size, PDI was0.365. And it stood in the fridge without any agglomeration during60days also confirmed successful PEGylation, which exhibited excellent stability in vitro and could have widespread prospect for biomedical application.We developed a pH-redox drug delivery system that loaded two anticancer drugs. First, anticancer drug MTX and pegylated NGO was linked via disulfide bond. Then DOX·HCL was loaded on NGO by π-π effect. The nano carrier was characterized using UV-vis, fluorescence spectrum, particle size. And the redox sensitive tests and drug release in vitro study were conducted. Study shows MTX with a loading content of77.45%and the release from the carrier is accelerated in the presence condition of10mM GSH, and achieving71.97%release of total MTX in56h. Beside, DOX·HCl with a loading content of62.67%and the release from the carrier is accelerated in the acid condition of pH5.0, and achieving61.31%release of total DOX·HC1in56h. After the intravenous injection, the drug-loading nanoparticles targeted to the tumor tissue with the EPR effect. In high GSH environment of tumor cells, disulfide bond was broken, MTX released quickly. And in the acid congdition, DOX-HC1released slowly, The designed nano drug carrier extended the body cycle, so as to realize the dual release of drug.