| ?- cyclodextrin(?-CD), with a special ring structure and cavity, can form inclusion complexes with different compounds such as organic molecules, rare gases, inorganic compounds by van der Waals force, hydrophobic interactions and hydrogen-bond interaction. In the field of medical research, ?-CD and its derivatives can effectively improve the drug solubility and bioavailability,reduce the toxic and side effect of drug, and be suitable to work as drug carrier for a variety of targeting drug delivery system. In the field of environmental management, P-CD can effectively promote the transformation of biological pollutants, remove organic pollutants and heavy metals from the environment.Super paramagnetic Fe3O4 nanoparticles have a lot of good properties, such as good magnetic responsiveness, biocompatibility, low toxicity, large specific surface area, and the advantages of easy recycling and reuse. Fe3O4 nanoparticles have widely been used in the fields of dye removal and magnetic targeting anti-cancer drug delivery system.Fe3O4 nanoparticles modified by ?-CD and its derivatives, are expected to enhance the carrying capacity of drugs and the adsorption capacity of organic pollutants by the inclusion effects of cyclodextrins. At the same time, integrated with super paramagnetic and excellent magnetic responsiveness of Fe3O4 nanoparticles, drug inclusion complexes with cyclodextrin and its derivatives are more apt to locate at cancerous tissue and enhance the adsorption ability for pollutant.In this article, we firstly prepared two kinds of inclusion complexes,podophyllotoxin-hydroxypropyl-?- cyclodextrin (POD-HP-?-CD) and camptothecin-sulfobutyl ether-?- cyclodextrin (CPT-SBE-p-CD) . The effects of cyclodextrin derivatives on the solubility and anticancer activities of the two drugs were also been studied. The results show that a 1:1 stoichiometric inclusion complex between POD and HP-?-CD can be formed by freeze-drying method. With the effect of HP-?-CD, the maximum solubility of POD can reach to 2.12 mg/mL;the average drug-loading is 2.71%, RSD is 0.56%, encapsulation efficiency is 34.19%.POD-HP-?-CD also can significantly inhibit the cell proliferation of HacaTand Hela cell lines in vitro. By the pH induction method, CPT and SBE-?-CD can form a 1:4 stoichiometric inclusion complex and the maximum solubility of CPT can be raised to 1.3 mg/mL. The drug-loading is 3.63%, RSD is 1.61%, and encapsulation efficiency is 92.43%.The inclusion complex of CPT and SBE-?-CD can effectively inhibit the cell proliferation of Hepg2 and NCI - 446 cell lines in vitro.In order to effectively enhance the targeting ability of the inclusion complex between anti-cancer drug and cyclodextrin for cancerous tissue, we plan to use bi-carbonyl imidazole grafted polyethylene glycol 6000 (PEG6000) as the coupling reagent to prepare ?-CD modified magnetic nanoparticles which can load anti-cancer drug in one pot under room temperature. To verify the feasibility of the coupling manner and the PEG coupling reagent, we at first graft Doxorubicin(DOX) to the surface of -NH2 modified Fe3O4 nanoparticles directly by the as prepared PEG6000 coupling reagent. The DOX loaded magnetic nanoparticles showed good anti-cancer effects both in Caenorhabditis elegans model and mice model. Compared to saline group, drug loaded magnetic nanoparticles show the best anti-tumor effects aiming at tumor-bearing mice, and the relative tumor inhibiting rate is 52.13%, followed by DOX group with a relative tumor inhibiting rate of 45.50%. The relative tumor inhibiting rate of the blank magnetic particles is 19.19%. Compared to saline group, the relative tumor inhibiting rate of the other three groups are all significant difference (P<0.05). The result shows that neither the coupling manner nor the PEG coupling reagent can affect the antitumous effect of chemotherapeutics. The average drug loading rate of three batches of DOX @ PEG @ MNPs was 0.986% (m/m), RSD was 0.32%.Based on the former study, in order to amplify the drug carrying category, and enhance the drug loading ratio of magnetic nanoparticles, we adopt PEG6000 coupling reagent to graft ?-CD molecular onto the surface of -NH2 modified Fe3O4 nanoparticles(CD@PEG@MNPs) and evaluate the drug loading ability of the magnetic nanoparticles for DOX(DOX @ CD @ MNPs).The average drug loading rate of three batches of DOX @ CD@ MNPs was 1.31% (m/m), RSD was 3.14%. The anti-tumor effects of DOX @ CD@ MNPs aiming at tumor-bearing mice were not as high as DOX group ( P<0.05 ), however, DOX @ CD@ MNPs still showed tumor inhibiting effect with a data of 25.50%, compared with saline group. Otherwise, DOX @ CD@ MNPs shows lower toxicity than DOX group, therefore, it maybe used as effective anti-cancer drug targeting system by further structural modification.Finally, we prepared Fe3O4 magnetic nanoparticles modified with Hydroxypropyl-P-cyclodextrin (HP-?-CD) and Polyethylene glycol 400 (PEG400) by a facile one pot homogeneous precipitation method. The nano particles showed excellent ability for the removal of Congo red(CR) from aqueous solutions. The value of the maximum adsorption capacity calculated according to the Langmuir isotherm model were 1.895 g/g, which are much high and about 19 times that of Fe3O4 nanoparticles. Desorp-tion study further indicates the good regeneration ability of the nanocomposites. The results suggest that the HP-?-CD/PEG400-modified Fe3O4 nanoparticles is a promising adsorbent for CR removal from aqueous solutions, and it is easily recycled owing to its large specific surface area and unique magnetic responsiveness. |
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