Preparation And Bioproperties Of Doxorubicin-loaded Magnetic Nanocarrier

Cancer is a leading cause of death worldwide because various factors may causecancer and it’s difficult to cure. Everyone is scared when it comes to cancer. Currently,available therapies for cancer are surgery, radiotherapy and chemotherapy.Chemotherapy is the most important one, but traditional chemotherapy will do harmto normal cell when it apply to treat cancer. Currently available therapies areinadequate and spur demand for improved technologies. Rapid growth innanotechnology towards the development of nanomedicine products holds greatpromise to improve therapeutic strategies against cancer. Nanocarriers are widelyused in cancer therapy due to their unique target strategy and drug deliverymechanism. They can improve the pharmacokinetic and pharmacodynamic profiles ofconventional therapeutics and may thus optimize the efficacy of existing anti-cancercompounds. In any cancer therapy, there is a balance between potential benefit andpotential harm of the treatment. The aim of any nano-application of a drug is to shiftthis balance in favor of the benefits.A variety of nanoscale drug delivery system including lip-based nanocarrier,nanocapsules, polymeric nanoparticles, polymeric micelles, dendrimers, inorganicnanoparticles, are currently under active investigation for delivery of small moleculedrugs as well as therapeutic macromolecules like proteins, peptides, aptamers, DNAand small interfering RNA(siRNA). These nanomedicines can successfully overcomemany drawbacks of free drugs and therapeutic molecules which include but are notlimited to poor solubility, non-selective activity, poor biodistribution andpharmacokinetics(PK), dose-limiting toxicity and also multi-drug resistance. Some ofthe salient advantages of nanocarriers include their increase drug stability, ability tosolubilize hydrophilic and hydrophobic agents, improved PK and biodistribution,tunable payload release, the ability to specifically target their payload to diseasedtissues and cells by modification of their surface chemistries, and their ability torespond to various internal and external stimuli for triggered release to achievetemporal and spatial control over the release of therapeutic payloads. When designing nanocarriers, one needs to address the variables which may lead to potential safetyconcerns including the material used for construction of the nanocarriers, doses orconcentration of the nanocarriers, the size, shape, surface charge, reactivity andsolubility. Due to the consideration of these variables could enable the development ofrobust nanosystem with many promising features. In the aspect of targeting strategy,nanocarrier has small size (less than200nm) that they can extravasate into the tumorsthrough enhanced permeability and retention (EPR) effect. Besides, Polymericmicelles can be functionalized for active targeting by chemically modifying theirsurface with targeting ligands that show a strong specificity for antigens or receptorsover-expressed on cancer cells. In the aspect of drug release, there are two ways torelease drugs: sustained release or stimuli-responsive release.Polymeric micelles exhibit several features that favor their utility for drugdelivery applications in in cancer. Polymeric micelle is a core-shell drug deliverysystem self-assembly by hydrophilic segments PEG and hydrophobic segment PLGA.Beyond the common advantage of nanocarriers, PEG-PLGA polymer is more stableand has long blood circulation. Magnetic iron oxide nanoparticles have raised muchinterest during the recent years due to their novel properties (superparamagnetism,high saturation field, blocking temperature, etc.) and potential applications in organicsynthesis, biotechnology and finally in medicine. The medicinal applications include:controlled drug delivery systems (DDS), magnetic resonance imaging (MRI),magnetic fluid hyperthermia (MFH), macromolecules and pathogens separation,cancer therapy and soon.We aim to prepare doxorubicin-loaded magnetic nanocarrier and study itsproperties. Firstly, we successfully synthesized Fe3O4nanoparticles through thermaldecomposition method, synthesized mPEG-PLGA copolymer through ring-openingpolymerization. The morphologies Fe3O4nanoparticles were observed by TEM, theimages showed that Fe3O4nanoparticles were spherical in shape and had a gooddispersibility in nanoscale. The size of Fe3O4nanoparticles were8nm. XRD analysisfuther proved the synthesis of Fe3O4nanoparticles. FTIR spectrum of mPEG-PLGAcopolymer indicaded that we synthesized mPEG-PLGA copolymer, has it has a good biocompatibility because the hemolytic rate is less than1%, no significantcytotoxicity can be seen for mPEG-PLGA indicated that it’s safe and nontoxicity.Then, we fabricated doxorubicine (DOX)-loaded magnetic nanocarrier byco-encapsulating Fe3O4nanoparticles and DOX into the core of mPEG-PLGAcopolymer via a facile dialysis method. FTIR analysis of Fe3O4nanoparticles, DOX,mPEG-PLGA and nanocarrier indicated that DOX and Fe3O4nanoparticles weresuccessfully loaded in the carriers. A satisfactory drug-loading content (4.63%) andencapsulation efficiency (27.53%) was achieve. TEM image showed nanoarriers werespherical in shape with average diameter of about70nm. Particle size of nanocarriersmeasured by TEM was smaller than those measured by dynamic light scattering (DLS)which was99.7±12.6nm due to the shrinking of polymer micelles during drying forthe preparation of TEM specimen. What’s more, the zeta potential of the carriers was-20.3±3.1mV and the polydispersity index were0.25, stability assay showed thatnanocarrier can remain stable for a long time. The release rate of DOX was found toincrease with decreasing pH, such that58.6%and83.7%of DOX were released whenstored in pH7.4and5.0, respectively.The cytotoxicity of the nanocarrier wereevaluated by MTT assay. The IC50value of free DOX and drug carrier was1.57μg/mL and15.01μg/mL in A549celles. The IC50value of free DOX and drug carrierwas2.81μg/mL and15.20μg/mL in Hela celles. Hela celles were treated withnanocarriers and were observe under fluorescence microscope to determaininternalization of DOX, the results showed that DOX was released into Hela cells andembedded in nucleus. Laser scanning confocal microscope (CLSM) futher revealedthe internatilization of DOX into nucleus and cytoplasm.