Preparation And Application Of Functionalized Nanocarriers Of Drug

It is well-known that nitric oxide (NO) is one of the important regulatorymolecules in vivo. the nitric oxide synthase(NOS)catalytic arginine generated NO. Itis well-known that nitric oxide (NO) is an endogenous free radical that plays a keyrole in the regulation of several physiological processes, such as the control ofvasodilation, platelet interaction with the vessel wall, immune responses, woundhealing and cellular communication. However, the physiological effects of NO arehighly dependent on concentration in the opposing beneficial and deleterious effects.Thus, it is very important to develop control NO release drugs in vivo. Malignanttumor (cancer), A serious threat to human health. With the society progress, theenvironment has been destroyed seriously and the rates of the human cancers haveincreased. In recent years, the human development of various new drugs and therapiesin clinical development for cancer treatment have made great progress, the currentmethod of treating cancer have surgery, radiotherapy and chemotherapy.Chemotherapy is one of the most promising ways to cure cancer. However,conventional chemotherapy have serious side effects. The drug nanocarriers withgood stability, good biocompatibility, easy modification and other characteristics, socombining the drug with a carrier for targeting, controlling delivery has become thehot topic of research. Therefore, it is significant to develop safe, stable, targeted andmulti-functional drug carriers for cancer diagnosis and therapy.In this study, based on the biocompatibility of chitosan modified the goldnanoparticles for control NO release to avoid the Oxidative stress. at the same times,PLGA are widely used drug carriers for controlled release since they offer manyadvantages like increased treatment effectiveness, reduced toxicity and are ofbiodegradable nature. Anticancer drug-loaded PLGA@MTX-AuNRs nanoparticles(NPs) were synthesized and were functionalized with fluorescence AS1411antinucleolin aptamers for site-specific targeting against tumor cells which overexpresses nucleolin receptors to imaging, targeted delivery of drugs and combinedchemotherapy and hyperthermia treatment, and avoid the limitations of singletherapy.and carried out the following work:1、In this work, Based on endogenous nitric oxide is one of the important regulatorymolecules in vivo, the physiological effects of NO are highly dependent onconcentration in the opposing beneficial and deleterious effects, Gold nanoparticlescan catalyze the endogenous NO donor nitrosothiols (GSNO) release NO.we present the synthesis of chitosan surface-modified gold nanoparticles (AuNPs@CS) as afunctional material to catalyze the controlled NO release from S-nitrosothiols (RSNO)which are one of the important endogenous NO donor in vivo. In this case, goldnanoparticles were used as the main catalytically active element, while chitosanmainly provided controlled effect. By using an amperometric technique and electronspin resonance (ESR) to detect the amount of NO release, we found the amount ofrelease NO is decreasing with the concentration of chitosan on the surface of goldnanoparitcles increasing. The mechanism is the cleavage of the RS-NO bond by theAuNPs@CS due to the formation of a RS-Au bond on the surface of AuNPs@CS.The available metallic surface area determines the amount of NO that can be released.Consequently, the controlled NO release in vivo can be realized via changing theamount of CS on the surface of AuNPs. It is a promising pathway for therapeuticsbecause ofAuNPs@CS biocompatibility and RSNO natural reservoir of NO.2、Base on most anticancer drugs are hydrophobic compounds of poorly water-soluble,toxic to limit its application. it is significant to solve these problems to using intoclinical of anti-cancer drugs. PLGA are widely used drug carriers for controlledrelease since they offer many advantages like increased treatment effectiveness,reduced toxicity and are of biodegradable nature. The particles were characterized byDynamic light scattering(DLS), scanning electron microscopy(SEM), transmissionelectron microscope (TEM) and UV-visible spectroscopy (UV). the entrapmentefficiency and drug loading of MTX@PLGA-NPs was investigated via UV method.The results showed that NPs prepared by the best condition were spherical in shape,and the particles diameters dPLGA=82.3±4.2nm. Cytotoxicity studies were carried outA549cells. Above all, we are succeed synthesized PLGA coated with hydrophobicanticancer drugs methotrexate (MTX) nanoparticles. In vitro release experiments, weare found that PLGA@MTX can quick release under acidic, and the cell toxicityexperiment found that the PLGA has high biological safety, and PLGA@MTX haveimprove the effectiveness of cell toxicity. This proved that PLGA can be used forcarrier of hydrophobic drugs.3、Base on PLGA are widely used drug carriers for controlled release since theyoffer many advantages like increased treatment effectiveness, reduced toxicity and areof biodegradable nature. In this work, anticancer drug-loaded PLGA-methotrexate–AuNRs nanoparticles (NPs) were synthesized and were functionalized with AS1411antinucleolin aptamers for site-specific targeting against tumor cells which over expresses nucleolin receptors and. The particles were characterized by Dynamic lightscattering(DLS), transmission electron microscope (TEM) and UV-visiblespectroscopy (UV). Cytotoxicity studies were carried out in two different cancer celllines, HEPG-2and normal cells LO-2. Confocal microscopy and flowcytometryconfirmed the cellular uptake of particles and targeted drug delivery. AuNRsgenerated photothermal effect and damage cancer cell. Combination of chemotherapyand photothermal effect could induce effectively apoptosis in cancer cell and avoidthe limitations of single therapy. The morphology analysis of the NPs proved that theparticles were smooth and spherical in shape with a size at107nm. Drug-loadingstudies indicated that under the same drug loading, the aptamer targeted NPs showenhanced cancer killing effect compared to the corresponding non-targeted NPs. Inaddition, the PLGA@MTX-AuNRs NPs exhibited high encapsulation efficiency andsuperior sustained drug release. The results confirmed that AS1411-PLGA@MTX-AuNRs NPs are potential carrier candidates for differential targeteddrug delivery and Combination of chemotherapy and photothermal effect couldinduce effectively apoptosis in cancer cell and avoid the limitations of single therapywhile normal cells without harm.