Synthesis Of Multifunctional Nanoparticles For Biomedical Applications

Nanobiotechnology is the hot spot of today’s scientific research, which is anintersection of nanotechnology and biotechnology.The functional nanoparticleshas agreat prospect in the biomedical field, such as biological probes, magnetictransfection and protein separation, targeted drug delivery, drug delivery, etc. To studythe interaction between the nanoparticles and the biologically active substance bymodifyingthe surface of the nanoparticles, in which lay the theoretical foundation forits subsequent applications in the field of biomedical. The ligand-exchange reactionmethodis based on the binding affinity of multidentateamine groups to the QDs orIONPs surface. After the ligand exchange, the NPs were converted from oil-soluble towater-soluble. At last, the stable multifunctional water-soluble nanoparticles wereobtained.The dendrimer PAMAM is a carrier, which is widely used in this paper. PAMAMdendrimers were prepared by a divergent synthesis scheme using the reagent excessmethod starting from EDA by consecutive Michael addition and ester amidationreaction. For the surface of PAMAM with numerous functional groups (amine,carboxyl, and hydroxyl), and it can be modified with different functionalities(conjugation of anti cancer drug and targeting moiety). After the modification of PEG,the pharmacokinetic properties of drugs and the drug distribution in vivo can beimprove, the stability in the body is increased, the toxicity and immunogenicity arereduced. And then the liand wascombined with nanoparticles, which is used asbiological probes and targeted drug delivery. A tumor targeted and pH-responsive drug release system that is based on folicacid (FA) conjugated to poly(ethylene glycol)(PEG)-modified dendrimers (PAMAM)with doxorubicin (DOX) andsuperparamagnetic iron oxide (Fe3O4) has beenconstructed andcharacterized.IONPs were stabilized by FA-PEG-G3.5PAMAMdendrimers. The anticancer drugDOX was conjugated to the dendrimer segments ofamino-stabilized IONPs using hydrazine as thelinker via hydrazone bonds, which areacid cleavable and can be used as an ideal pH-responsive drugrelease system. Notably,these novel nanoparticlescontaining DOX conjugates showed great potential forapplicationin both MRI detection and cancer therapy by virtue oftheir targetingfunction, in addition to EPR accumulation, whichallowed the anticancer drug to beorientated directly to thetarget sites, although the nanoparticles without tagetingmoiety.A tumor targeted and drug-loaded system that is based on folic acid (FA)conjugated to poly(ethylene glycol)(PEG)-modified dendrimers (PAMAM) withpaclitaxel (PTX), Cy5.5fluorophore and superparamagnetic ironoxide (IONPs) hasbeen constructed and characterized. And through a variety of detection methods tocharacterize the size of its structure, morphology, both the physical and chemicalproperties were studied. The attached FA could facilitate the use of the conjugates as afolate receptor-targeted drug deliverysystem. TheCLSMpictures of cell in vitro canprove that the role the targeting molecule FA plays in the uptake of NPconjugates bythe cell.These novel PTX-loaded conjugates have the potential to enhance the effectof fluorescenceimaging, MRI contrast and cancer therapy in the course of deliveringdrugs to target sites.This provides the research foundation for tumor detection andtargeted therapy.We have developed an imaging system by co-conjugating QDs and IONPs withmPEG-G3.5PAMAM for both of MRI and fluorescent imaging concurrently, whichcombination of QDs and IO as a single probe strives to improve imaging withpractical clinical feasibility andthe anti-VEGF was selected as the targetingmoiety.These preliminarydata demonstrated that the conjugation of anti-VEGF moleculesto the surface of the NPs, which favors the anti-VEGF receptorrecognition,was responsible for the targeting ability of anti-VEGF-PEG-G3.5-QDs@IONPs, andin turn beneficial to theirentry into the cells through endocytosis or macropinocytosis.It isparently seen that anti-VEGF conjugated NPs exhibitedefficientreceptor-mediated endocytosis in VEGF receptoroverexpressingcancer cells, ascompared to non-targeted NPs.Conjugation of hybridnanoparticles show better cancerimaging ability as an MRcontrast agent in vivo and fluorescent imaging effects exvivo asthe result of the combined anti-VEGF, thereby greatly improvingthe efficacyof imaging.The same applications of targeting mechanism of targeting molecules anti-VEGFspecific binding of VEGF overexpressing of the tumor surface, after preparing thefluorescent the targeted drug loading release system. The ligand-exchange reaction isbased on the binding affinity of the anticancer drugs DOX modified-G3.5PAMAM tothe QDs surface. Doxorubicin and quantum dots are connected through this effectivemethod, by this way the QDs were converted to high quantum yield ofwater-soluble complexes so that the composite nanoparticles can play an importantrole in cancer targeted treatment. Meanwhile, the PEGylation of PAMAM dendrimermodified onto the surface of the nanoparticle, which greatly improve the stability ofquantum dots. And the good biocompatibility and low toxicity of PEG and PAMAMmake its application in biology.Optical and magnetic resonance (MR) imaging probes were integrated byconjugating DTPAgadolinium(Gd) derivative to quantum dot based FA-PEG-G3.5PAMAM. It is known that carboxyl canbe used to stabilize QDs with oleic acidcoating, and obtained water-soluble macromolecular fluorescent QDs. The remainingcarboxyl groups can chelate Gd to preparea dual probe, which contains MR imagingand fluorescence imaging molecules, then through a series of characterizationmethods to characterize its structure.The dual probe shows better cancer imaging ability as an MRcontrast agent in vivo and fluorescent imaging effects ex vivo astheresult of the combined FA, thereby greatly improvingthe efficacy of imaging.