Preparation Of Functionalized Carbon-encapsulated Magnetic Nanocomposites And Their Performance In Controlled Release

Magnetic targeted drug delivery system has attracted increasing attentions inthe field of drug delivery, because it can accomplish the targeted, controlledrelease and hyperthermia simultaneously, so as to significantly improve thetreatment efficiency for tumor and reduce the side effect. As a kind of smartdruge delivery carrier, magnetic thermosensitive nanocomposites have receivedconsiderable interest, which are obtained by incorporating magneticnanoparticles in the thermosensitive polymer. On one hand, magneticcomponents could be firstly targeted at specific tumor issue in the presence of anexternal magnetic field and realize hyperthermia; On the other hand,functionalized magnetic components with a thermosensitive organic layer asdrug containers could achieve controlled release induced by their response to thetemperature change, thus overcoming several limitations of conventional cancertherapy.However, magnetic nanoparticles could hardly be stabilized in dispersionbecause of their own magnetism. Therefore, the most crucial in the preparationof magnetic thermosensitive nanocomposites is obtaining stable, evenlydispersed magnetic nanoparticles and provide a supporter for polymer. Recently, variable carbon nanomaterials are among the widely used carriers for core/shellstructured composite, of which the properties of good chemical, mechanical andthermal stabilities are suitable for the accommodation of polymer layer.Under such background, this paper focuses on the preparation,characterization and preliminary application of functionalizedcarbon-encapsulated magnetic microspheres. It contains thermosentitivemicrospheres with a carbon core (CMS/PNIPAM), solid magneticthermosensitive microspheres (TSMCMSs)，hollow microspheres (TSCHMSs)and their performance in hyperthermia and drug delivery. Moreover, theinteractions between magnetic thermosensitive microspheres and protein wereinvestigated by spectroscopy, which provide the foundation for their applicationin targeted drug delivery.The main research contents and conclusions are as follows:1. Preparation of CMS/PNIPAM: the carbon microspheres produced bychemical vapor deposition were chose as carriers, then, oxidized-carbonmicrospheres were obtained by mixed-acid oxidization to produce enoughoxygen-containing functional groups on their surface; the siliane agent3-(trimethoxysilyl)-propyl methacrylate (MPS) was used to functionalize theoxidized-carbon microspheres so as to generate a hydrophobic surfaces on themicrospheres; thereafter, the as-synthesized particles were used as seeds in theradical polymerization of N-isopropylacrylamide to introduce a thermosensitivepolymer shell onto the surfaces of the CMSs in the presence of an initiator and acrosslinker. The morphology and structures of the composite microspheres werecharacterized by field emission scanning electron microscopy (FESEM),transmission electron microscopy (TEM), Fourier transformation infraredspectroscopy (FTIR), thermogravimetry (TG) and dynamic light scattering(DLS). Results indicate that: the optimum synthesis condition is12h forreaction time and15for crosslinking density; according to TEM analysis, hybridmicrospheres prepared under this condition have a polymer layer with a thickness of about25nm and a swelling ration (SR) of2.6; CMS/PNIPAMshows apparent thermosensitivity and its lower critical solution temperature(LCST) takes place at about30℃; the thickness of polymer layer could beadjusted by the crosslinking agent’s concentration; both computationalsimulation and experiments demonstrate that5-fluorouracil could be chosen as amodel drug for evaluating the loading efficiency of CMS/PNIPAM; moreover,the lower crosslinking density could improve the loading efficieny, whencrosslinking density increased from15to25, their saturated loading amountdecreased from17.91to15.84mg/g.2. Preparation of TSMCMSs: firstly, carbon-encapsulated magneticmicrospheres were synthesized from ferrocene and acetone by solvothermalmethod; then magnetic thermosensitive microspheres were prepared usingcarbon-encapsulated magnetic microspheres as cores, N-isopropylacrylamide asthermosentitive monomer, potassium persulfate as initiator and N, N-methylenebisacrylamide as crosslinker. Results demonstrate that: the grafting ration ofpolymer is8.77%; TSMCMSs are superparamagnetic, whose saturatedmagnetism is13.75emu/g; they generate heat when inductive magnetic field isapplied to them and have a specific absorption rate of77.0W/g, showing goodpotential for hyperthermia; they have a hydrodynamic diameter of280nm withan LCST at around45℃and a SR of7.0; the controlled release experimentsshow the microspheres have excellent drug-loading and temperature-triggereddrug-release ability for5-fluorouracil.3. Preparation of TSCHMSs: hollow magnetic microspheres were firstlyobtained from ferric chloride, ethylene glycol and polyvinylpyrrolidone; thenmagnetic thermosensitive microspheres with hollow Fe3O4as cores weresynthesized using carbon nanomaterial as a steric stablizier and polymersupporter, N-isopropylacrylamide as thermosentitive monomer, potassiumpersulfate as initiator and N, N-methylene bisacrylamide as crosslinker; Resultsindicate that the grafting ration of polymer is5.51%; TSCHMSs have an LCST at around43℃, a SR of4.1and show apparent magnetism with a magnetizationof56.9emu/g at5kOe; under an inductive magnetic field, they increase thetemperature of the medium to45℃in18minutes and have a specificabsorption rate of240W/g, showing potential for hyperthermia as thermoseeds;according to the drug loading and release experiment, TSCHMSs have asaturated loading amount of30.3mg/g at4h; the cumulative release fraction is18.8%and36.2%at35℃and50℃respectively, showing excellentdrug-loading and controlled release ability for5-fluorouracil.4. Spectroscopic interactions between functionalized microspheres andprotein: at25℃, TSMCMSs could quench the fluorescence of BSA and thequenching is dependent on the concentration of TSMCMSs; by fitting theStern-Volmer equation, it can be concluded that it is a static quenching; theirinteraction is spontaneous and based on hydrogen bond; moreover, UV-Visanalysis demonstrates that the existence of TSMCMSs induced theconformational change of BSA; the circular dichroism results confirm theskeleton of BSA become loose after interacting with TSMCMSs; when itsconcentration increases from0to30mg/L, the random coil content of thesecondary structure increases from33.0%to36.0%. Hollow TSCHMSs have thesimilar interaction with BSA. However, owing to their smaller nanoparticle size,they quench BSA more deeply and make the skeleton of BSA looser. Moreover,the toxicity of the carriers should be further discussed in the biologicenvironment.