利用負載阿霉素的金屬有機框架涂層磁性納米顆粒精準治療結腸癌

2024年9月，浙江大學材料科學與工程學院；伊利諾伊大學芝加哥分校藥學院藥學系；浙江大學動物科學學院應用生物資源研究所，浙江蠶蜂資源利用與創新重點實驗室 (School of Materials Science &Engineering,Zhejiang University, Hangzhou, Zhejiang 310027, China；Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, 60607, United States；Key Laboratory of Silkworm and Bee Resource Utilization and Innovation of Zhejiang Province,Institute of Applied Bioresource Research, College of Animal Science, Zhejiang University, Hangzhou, Zhejiang 310058,China;) Honglin Jiang老師研究團隊在《Acs Applied Materials & Interfaces》上發表論文：

“Precision Treatment of Colon Cancer Using Doxorubicin-Loaded Metal-Organic-Framework-Coated Magnetic Nanoparticles"

“利用負載阿霉素的金屬有機框架涂層磁性納米顆粒精準治療結腸癌"

Abstract：

Due to the limited efficacy and evident side effects of traditional chemotherapy drugs attributed to their lack of specificity and selectivity, novel strategies are essential for improving cancer treatment outcomes. Here, we successfully engineered Fe₃O₄ magnetic nanoparticles coated with zeolitic imidazolate framework-8 (ZIF-8). The resulting nanocomposite (Fe₃O₄@ZIF-8) demonstrates efficient adsorption of a substantial amount of doxorubicin (DOX) due to the porous nature of ZIF-8. The drug-loaded nanoparticles, Fe₃O₄@ZIF-8/DOX, exhibit significant accumulation at the tumor site in SW620 colon-cancer-bearing mice when guided by an external magnetic field. Within the acidic microenvironment of the tumor, the ZIF-8 framework collapses, releasing DOX and effectively inducing tumor cell death, thereby inhibiting cancer progression while not causing undesired side effects, as confirmed by a variety of in vitro and in vivo characterizations. In comparison to free DOX, Fe₃O₄@ZIF-8/DOX nanoparticles show superior efficacy in colon cancer treatment. Our findings suggest that Fe₃O₄@ZIF-8 holds promise as a carrier for small-molecule drug adsorption and its ferromagnetic properties provide drug targeting capabilities, thereby enhancing therapeutic effects on tumors at the same drug dosage. With excellent biocompatibility, Fe₃O₄@ZIF-8 demonstrates potential as a drug carrier in targeted cancer chemotherapy. Our work suggests that a combination of magnetic targeting and acid-responsiveness holds great promise for advancing targeted cancer therapy in precision nanomedicine.

摘要：

由于傳統化療藥物缺乏特異性和選擇性，其療效有限，副作用明顯，因此新的策略對于改善癌癥治療效果至關重要。在這里，我們成功地設計了包裹有沸石咪唑酸框架-8 （ZIF-8）的Fe3O4磁性納米顆粒。由于ZIF-8的多孔性，所得到的納米復合材料（Fe3O4@ZIF-8）能夠有效吸附大量的阿霉素（DOX）。負載藥物的納米顆粒Fe3O4@ZIF-8/DOX在外部磁場引導下，在SW620結腸癌小鼠的腫瘤部位表現出顯著的積累。在腫瘤的酸性微環境中，ZIF-8框架崩潰，釋放DOX并有效誘導腫瘤細胞死亡，從而抑制癌癥進展，同時不會引起不良副作用，這一點得到了各種體外和體內表征的證實。與游離DOX相比，Fe3O4@ZIF-8/DOX納米顆粒在結腸癌治療中表現出療效。我們的研究結果表明，Fe3O4@ZIF-8有望成為小分子藥物吸附的載體，其鐵磁特性提供了藥物靶向能力，從而在相同藥物劑量下增強對腫瘤的治療效果。Fe3O4@ZIF-8具有良好的生物相容性，具有作為靶向癌癥化療藥物載體的潛力。我們的工作表明，磁性靶向和酸反應性的結合對于推進精確納米醫學中的靶向癌癥治療具有很大的希望。

該論文中，SW620的體外培養是使用Ausbian特級胎牛血清完成的。