高分散共轭聚合物-金属有机框架纳米立方体的制备及抗肿瘤应用

Nano-sized metal-organic frameworks possess uniform pores and high specific surface area of traditional frameworks, and enhanced permeability and retention effect of the nanomaterials, can be used as a new class of drug carriers. Recently, these materials have been heavily explored in the fields of drug delivery and tumor theranostics. However, chemotherapy using these nanoparticles as drug delivery vehicles alone cannot lead to high tumor inhibition efficiency. Other therapeutic modalities should be combined to improve the therapeutic effect. In this work, a general approach for the synthesis of conjugated polymer (CP)-zeolitic imidazolate framework-8 (ZIF-8) nanocubes was developed. With the assistance of cetyl trimethyl ammonium bromide, hydrophobic conjugated polymer poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)-alt-4,7(2,1,3-benzothiadiazole)] (PCPDTBT) was transferred into aqueous solution through microemulsion method. After mixing with zinc ions and 2-methylimidazole, PCPDTBT can be encapsulated within ZIF-8, forming nanocubes with an average size of around 60 nm. After surface modification with amphiphilic block copolymer F127, the obtained nanocubes exhibited high dispersity and colloidal stability in aqueous solutions. The hydrodynamic diameter of the F127 coated nanocubes was around 62 nm, and did not change obviously after storing for 7 d. The nanocomposites exhibited high drug loading capacity, and can release drug in an acidic responsive manner, which was beneficial for chemotherapy. Due to the strong absorption of PCPDTBT in the near infrared region, the nanocubes can be used for photothermal therapy with a 730 nm laser. ZIF-8 coating also improved the photothermal conversion efficiency of PCPDTBT to around 42.5%, which can be useful for efficient photothermal therapy. Animal experiments were performed to demonstrate the antitumor ability of the nanocubes. With the combination of chemotherapy and photothermal therapy, the drug loaded nanocubes can inhibit the tumor growth in vivo efficiently under laser irradiation, and meanwhile, do not cause obvious damage to normal organs. Therefore the obtained nanocubes can be effective antitumor a ents.