Preparation of Highly-dispersed Conjugated Polymer-Metal Organic Framework Nanocubes for Antitumor Application

doi:10.6023/A23030095

Abstract

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 agents.

Key words: metal-organic frameworks, conjugated polymer, nanocubes, photothermal effect, combined therapy

Cite this article

Bo Sun, Wenwen Ju, Tao Wang, Xiaojun Sun, Ting Zhao, Xiaomei Lu, Feng Lu, Quli Fan. Preparation of Highly-dispersed Conjugated Polymer-Metal Organic Framework Nanocubes for Antitumor Application[J]. Acta Chimica Sinica, 2023, 81(7): 757-762.

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Fig. & Tab. 6

Figure 1. Schematic illustration of the fabrication of conjugated polymer-MOF nanocubes for the combination therapy of tumor

Figure 2. TEM images of the nanoparticles obtained by adding F127 (a) immediately, (b) 10 min, and (c) overnight after the injection of zinc nitrate; (d) hydrodynamic size distributions of ZIF-8@F127 nanocubes

Figure 3. (a) TEM image of CZF; (b) absorption spectrum of CZF solution and the chemical structure of PCPDTBT; temperature elevation of CZF solution after illuminated with 730 nm laser under (c) different power densities and (d) absorbance; (e) photothermal stability of CZF; (f) the linear fitting curve of the time data versus －ln θ

Figure 4. (a) Cumulative release of DOX from CZF/DOX under different conditions; (b) cell viabilities after incubated with CZF and CZF/ DOX at different concentrations

Figure 5. (a) Infrared thermal images and (b) temperature elevation curves at the tumor sites of the mice under laser irradiation after the injection of saline and CZF/DOX solution; (c) tumor volumes and (d) body weights of the mice during different treatments; (e) the weights and (f) the photographs of the isolated tumors after the treatments

Figure 6. H&E staining of the major organs and the tumors of the mice after the treatments

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