Drug-loaded Nano-micelles And Three Dimensional Organic Framework Based On Four-arm Rigid Structure Unit

Adamantane is a highly systematic cage-like structured hydrocarbon with a high rigid ring system.Due to its good lipophilicity,low biotoxicity,unique three-dimensional structure,good thermal and oxidative stabilities,adamantane has a broad application space in chemical industry,biomedicine,functional polymer materials,special functional materials and other fields.Nowadays,multifunctional polymers,such as stimuli-responsive polymers and organic frameworks,have attracted more and more attention.In this work,a series of pH-sensitive polymeric micelles and organic three dimensional framework based on adamantane were designed and synthesized.The pH-sensitiveness of the polymeric micelles and the gas adsorption abilities of the organic 3D framework were further studied.The detailed contents were listed as follows:pH-sensitive star-shaped copolymers(Ad-[P(EMA-co-MAA)-b-PPEGMA]4)were synthesized using poly(ethyl methacrylate)(PEMA)as the hydrophobic segment and poly(poly-(ethylene glycol)methyl ether monomethacrylate)(PPEGMA)as hydrophilic segment and poly(methacrylic acid)(PMAA)as the pH-sensitive segment.Paclitaxel(PTX)was used as a model drug and loaded into the star polymeric micelles.The relationship among polymer microstructure,micellar mesoscopic structure,drug release performance was studied.The results showed that the polymeric micelles possessed high stability and good pH-sensitiveness.In vitro drug release studies revealed that less than 20%of the PTX released at an acidic condition of pH 1.2,whereas more than 70%was released within the same time interval at pH 6.8.In vitro cytotoxicity suggested that the low cytotoxicity of the blank micelles,while the PTX-loaded micelles providing the cytotoxicity to MCF-7 cells.pH-sensitive random star-shaped copolymers(Ad-P(EMA-co-MAA)4)were synthesized.The self-assembled properties of the random copoymers were studied under the different conditions.The effects of solvent,polymer concentration and dialysis time on the self-assembly behavior of Ad-P(EMA-co-MAA)4 were investigated.In vitro drug release behavior of the PTX-loaded micelles suggested that the release rate of PTX could be influenced by the pH values of environment.In the acidic condition,less than 20%PTX were released from the micelles,while 78%PTX were released under the alkaline condition.The cytotoxicity assay indicated the low cytotoxicity of the blank micelles and significant drug efficiency of the PTX-loaded micelles.Organic three dimensional framework(MF-1)was designed and synthesized via Sonogashira-Hagihara coupling of 1,3,5,7-tetra(1,3-dibromophenyl)adamantane "knot" and 1,3,5,7-tetra(alkynylbenzene)adamantane "linker" MF-1 showed good chemical stability and thermal stability due to the adamantane-based monomers.The BET surface area and pore size distribution of MF-1 was 438 m2 g-1 and 0.61-0.77 nm,respectively.In addition,adsorption capacities of MF-1 for small gas molecules(CO2,CH4,N2,)were investigated in details.