用于癌症光动力疗法-化疗联合疗法的 CPP10 靶向光活化 MOF 纳米系统

IF 6.7 3区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Journal of Science: Advanced Materials and Devices Pub Date : 2024-06-25 DOI:10.1016/j.jsamd.2024.100761
Jiahui Kong, Mengru Cai, Rongyue Zhu, Yongqiang Zhang, Yuji Du, Xiaohong Jing, Yufei Sun, Rongrong Chang, Changhai Qu, Xiaoxv Dong, Jian Ni, Xingbin Yin
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引用次数: 0

摘要

近年来,胃癌的发病率逐年上升。姜黄素(CUR)在治疗胃癌方面显示出巨大的潜力,但其生物利用度低、疗效差,阻碍了它在临床上的广泛应用。此外,在光动力疗法中,姜黄素被发现是一种出色的光敏剂。本研究采用铁基金属有机框架(MOF)铁四(4-羧基苯基)卟啉(Fe-TCPP,FT)作为光敏剂和单核剂。天然抗肿瘤活性成分 CUR 同时作为化疗剂和光敏剂被载入纳米粒子 CUR@FT (CF)。最后,在纳米颗粒表面修饰了一种细胞穿透肽(CPP10),构建了一种药物递送系统(CPP10-PEG@CUR@FT,CCF),该系统可以主动靶向肿瘤细胞,同时发挥化疗和光动力疗法的协同治疗作用。FT纳米颗粒的高载药量和pH敏感性为CUR的高效递送提供了良好的载体。聚乙二醇(PEG)共轭 CPP10(PEG-CPP10)涂层可使纳米颗粒特异性地靶向胃癌细胞,显著改善纳米颗粒在体内和体外的吸收,提高生物安全性。我们评估了 FT 作为给药载体的热稳定性、载药能力和安全性。我们还评估了各种纳米颗粒的体外光动力性能和毒性,以及 CPP10-PEG@CUR@FT 的靶向性和生物相容性。结果表明,CPP10-PEG@CUR@FT可特异性靶向肿瘤细胞,在光照下对胃癌细胞(MKN45)的杀伤作用远强于游离CUR。其对其他器官和组织的毒性和副作用较低,具有良好的生物安全性。实验结果表明,FT 和 CUR 在光动力治疗和化疗中具有协同作用。总之,我们的新型 CUR 靶向纳米给药系统将光动力疗法和化疗结合起来治疗肿瘤,具有显著的优势。这种方法引入了化疗、光动力疗法和靶向给药相结合的新概念,有可能为胃癌的临床治疗提供一种新策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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CPP10-targeted photoactivatable MOF nanosystem for combined photodynamic Therapy−Chemotherapy of cancer

The annual prevalence of gastric cancer has increased in recent years. Curcumin (CUR) has shown great potential in the treatment of gastric cancer; however, its low bioavailability and poor efficacy hinder its widespread clinical application. Additionally, CUR has been found to be excellent photosensitizer in photodynamic therapy. In this study, the Fe-based metal-organic framework (MOF) Fe Tetrakis (4-carboxyphenyl) porphyrin (Fe-TCPP,FT) was used as a photosensitizer and mononuclear agent. The natural anti-tumor active ingredient CUR was loaded as both a chemotherapeutic agent and photosensitizer to form the nanoparticles CUR@FT (CF). Finally, a cell-penetrating peptide (CPP10) was modified on the surface of the nanoparticles to construct a drug delivery system (named CPP10-PEG@CUR@FT, CCF) that could actively target tumor cells while exerting a synergistic therapeutic effect of chemotherapy and photodynamic therapy. This can improve the efficacy of CUR as a chemotherapeutic drug or photosensitizer, and the high drug load and pH sensitivity of FT nanoparticles provide an excellent carrier for the efficient delivery of CUR. The polyethene glycol (PEG)-conjugated CPP10 (PEG-CPP10) coating allows nanoparticles to specifically target gastric cancer cells, significantly improving the absorption of nanoparticles in vivo and in vitro and improving biosafety. We evaluated the thermal stability, drug loading capacity, and safety of FT as a drug delivery vehicle. We also assessed the in vitro photodynamic performance and toxicity of various nanoparticles and the targeting and biocompatibility of CPP10-PEG@CUR@FT. CPP10-PEG@CUR@FT could specifically target tumor cells, and its effect on killing gastric cancer cells (MKN45) under light was much stronger than that of free CUR. Its toxicity and side effects to other organs and tissues are low, offering good biosafety. The experimental results showed that FT and CUR exerted synergistic effects on photodynamic therapy and chemotherapy. In summary, our novel CUR-loaded targeted nano drug delivery system offers significant advantages by combining photodynamic therapy and chemotherapy for tumor treatment. This approach introduces a new concept for integrating chemotherapy, photodynamic therapy and targeted drug delivery, potentially providing a new strategy for the clinical treatment of gastric cancer.

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来源期刊
Journal of Science: Advanced Materials and Devices
Journal of Science: Advanced Materials and Devices Materials Science-Electronic, Optical and Magnetic Materials
CiteScore
11.90
自引率
2.50%
发文量
88
审稿时长
47 days
期刊介绍: In 1985, the Journal of Science was founded as a platform for publishing national and international research papers across various disciplines, including natural sciences, technology, social sciences, and humanities. Over the years, the journal has experienced remarkable growth in terms of quality, size, and scope. Today, it encompasses a diverse range of publications dedicated to academic research. Considering the rapid expansion of materials science, we are pleased to introduce the Journal of Science: Advanced Materials and Devices. This new addition to our journal series offers researchers an exciting opportunity to publish their work on all aspects of materials science and technology within the esteemed Journal of Science. With this development, we aim to revolutionize the way research in materials science is expressed and organized, further strengthening our commitment to promoting outstanding research across various scientific and technological fields.
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