Design, Preparation And Properties Of Multifunctional Fluorescent Nanocarriers Based On Polyphosphazene Materials

With the development of nanotechnology, nanomaterials have been found theirpotential as drug carriers. Nanomaterials and nanotechnology are applied in thedrug release systems in order to increase the dissolution, the intake and thetarget activity. Thus, the effectiveness of the drug can be greatly improved. Asdrug release systems, nanocarriers, especially the recent multifunctionalnanocarriers, have their bright future in the field of medical treatment andmedicine. Therefore, the research and development of novel multifunctionalnanocarriers have been a hot spot for our researchers. Till now, the technicaldifficulties of synthesis are still the lack of researches on multifunctionalnanocarriers. Our researchers are trying to find an easy way to prepare for thebase material of the novel multifunctional nanocarriers.Poly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)] materials can beeasily synthesized under the mild conditions. Moreover, when used as thematrix of multifunctional nanocarrier, poly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)] materials also possess many merits:(1) Various nanocarrierscan be designed and prepared based on these particular materials;(2) Poly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)] materials have the sameexcellent properties as other polyphosphazene materials, especially thebiocompatibility;(3) Poly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)]materials have their highly crosslinking structures which lead to excellentthermal stability and solvent resistance;(4) Poly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)] materials are synthesized through the crosslinking reactionof hexachlorocyclotriphosphazene (HCCP) and4,4-sulfonyldiphenol (BPS),which means the backbone of poly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)] materials possesses active N atoms from HCCP and active hydroxyl groups from BPS;(5) Poly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)] materials possess relatively high drug loading rate andexcellent drug slow-release performance;(6) It is very important that poly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)] materials possess excellentintrinsically fluorescent properties. This work is mainly focused on the designand preparation of multifunctional nanocarriers based on poly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)] materials. The detailedresearch contents and results are as follows:1. The study first discovers that poly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)] materials, including nanotubes and microspheres, exhibitexcellent intrinsically fluorescent properties. The poly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)] fluorescent nanoparticles can be well dispersed inboth aqueous and organic media. The formation of highly crosslinkingstructure based on HCCP not only leads to enhancement of optical properties,including fluorescent intensity and photobleaching stability, but also endowsthe complex with outstanding solvent resistance and thermal stability.2. A facile strategy has been successfully developed to fabricate hollowfluorescent poly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)] nanocarrier.The mean diameter of interior cavities can be well adjusted (typically in arange from100to300nm). These nanocarriers manifest high drug storagecapacity (380mg g-1,406mg g-1and435mg g-1of doxorubicinhydrochloride as the increase of the interior cavity) and excellent sustainedrelease property (up to15days). Moreover, such nanocarriers possessoutstanding fluorescent property, justifying their promising applications in drugdelivery.3. In situ surface-initiated atom transfer radical polymerization (ATRP) ofpoly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)] materials is fullydiscussed. As a model, poly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)]microspheres are functionalized via ATRP. A core-shell structure, i.e.microspheres coated with a polystyrene shell, is successfully formed and thenumber-average molecular weight of the grafted polymer chains can be wellcontrolled. Furthermore, the polystyrene-grafted microspheres are still active for further block copolymerization of methyl methacrylate. Based on thisfunctionalization strategy, we have then successfully grafted poly(N-isopropylacrylamide) onto the surface of poly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)] nanotubes forming a new kind of fluorescenttemperature sensitive nanocarrier. Its drug storage capacity can reach up toabout233mg g-1doxorubicin hydrochloride. The drug release can be wellcontrolled by adjusting temperature. Moreover, this nanocarrier also exhibitsexcellent fluorescent property.4. A new strategy to prepare fluorescent magnetic nanocarrier based oncarbon nanotubes has been successfully developed. First, on the basis ofexternal template self-assembly mechanism, carbon nanotubes are uniformlycoated by poly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)] nanocoating,which endows the carbon nanotubes with excellent fluorescent property. Then,based on the complexing capability of active N atoms in the backbone of poly[cyclotriphosphazene-co-(4,4-sulfonyldiphenol)] coating, Fe3O4nanoparticlesare easily deposited onto the surface of nanotubes, which endows the carbonnanotubes with excellent magnetic properties. Moreover, this nanocarriermanifests relatively high drug storage capacity (106mg g-1doxorubicinhydrochloride) and excellent sustained release property (up to10days). Thehemolysis test indicates that the fluorescent magnetic nanocarrier possessesoutstanding biocompatibility.