Synthesis of acid-activated reversible conversion supramolecular nanoplatform: application in drug delivery and anti-tumor activity

IF 2.8 4区工程技术 Q2 POLYMER SCIENCE

Macromolecular Research Pub Date : 2023-11-21 DOI:10.1007/s13233-023-00209-7

Cuiting Yang, Xiangyu Chen, Jinkui Teng, Shuai Chen, Jianmei Yang, Xiaoqing Liu, Junnan He, Jin Zhang, Yan Zhao

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Abstract

Supramolecular nanoplatforms with stimuli-responsive behavior feature sensitive performance and effective drug delivery, which are desirable as intelligent drug delivery systems. Generally, tumor cells are characterized by excessive acid production, resulting in a lower pH in the tumor microenvironment (pH < 6.5) than in normal tissues (pH ≈7.4) and providing the possibility for the drug delivery system to exploit this decrease in pH as a trigger for drug release. Here, an acid-sensitive supramolecular nanoplatform (CM-β-CD/FC₁₂⁺Br⁻ NPs) with assembly/disassembly properties was designed and constructed, which was exploited to capture, deliver, and release anti-tumor compound CSL. 2D NOESY was utilized to examine the host–guest interaction and the potential mechanism for CM-β-CD/FC₁₂⁺Br⁻ NPs loading CSL. CM-β-CD/FC₁₂⁺Br⁻ NPs present good blood compatibility. Cytotoxicity assay revealed that CSL-loaded NPs display minimal toxicity against normal cells BEAS-2B and good anticancer ability against five human cancer cell lines, especially for Human hepatoma cell line SMMC-7721. In addition, cell apoptosis and cycle assay further verified that CSL-loaded NPs-induced apoptosis in SMMC-7721 cells up to ~ 93%, as well as blocking the cells in G0/G1 phase and inhibiting the proliferation of SMMC-7721 cells in a dose-dependent manner. We expect that CM-β-CD/FC₁₂⁺Br⁻ NPs will be potential acid-answered drug delivery candidates.

Graphical Abstract

The acid-activated reversible conversion CM-β-CD/ FC₁₂⁺Br⁻ nanoparticles (NPs) are constructed to trap, deliver and release anti-liver cancer compound Celastrol (CSL). CSL-loaded NPs display a high release rate of CSL at the acidic environment within hepatoma cells, exhibit a high cytotoxicity and apoptotic rate for SMMC-7721 cells and arrest the cells at G0/G1 phase in a dose-dependent manner. CM-β-CD/ FC₁₂⁺Br⁻ NPs help to realize liver cancer treatment.

Abstract Image

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酸活化可逆转化超分子纳米平台的合成:在药物传递和抗肿瘤活性中的应用

具有刺激响应行为的超分子纳米平台具有敏感的性能和有效的给药性能，是智能给药系统的理想选择。通常，肿瘤细胞的特点是产生过多的酸，导致肿瘤微环境中的pH值(pH < 6.5)低于正常组织(pH≈7.4)，并为药物递送系统提供了利用pH值降低作为药物释放触发器的可能性。本文设计并构建了一种具有组装/拆卸特性的酸敏感超分子纳米平台(CM-β-CD/FC12+Br−NPs)，用于捕获、传递和释放抗肿瘤化合物CSL。利用二维NOESY分析了CM-β-CD/FC12+Br−NPs加载CSL的主客体相互作用和潜在机制。CM-β-CD/FC12+Br - NPs具有良好的血液相容性。细胞毒性实验表明，负载csl的NPs对正常细胞BEAS-2B的毒性很小，但对5种人类癌细胞系，特别是对人肝癌细胞系SMMC-7721具有良好的抗肿瘤能力。此外，细胞凋亡和周期实验进一步证实，负载csl的nps诱导SMMC-7721细胞凋亡高达93%，并在G0/G1期阻断细胞，并以剂量依赖性方式抑制SMMC-7721细胞的增殖。我们预计CM-β-CD/FC12+Br - NPs将成为潜在的酸应答药物递送候选者。摘要构建了酸激活可逆转化CM-β-CD/ FC12+Br -纳米颗粒(NPs)，用于捕获、传递和释放抗肝癌化合物Celastrol (CSL)。负载CSL的NPs在肝癌细胞内的酸性环境下显示出高的CSL释放率，对SMMC-7721细胞表现出高的细胞毒性和凋亡率，并以剂量依赖的方式将细胞阻滞在G0/G1期。CM-β-CD/ FC12+Br−NPs有助于实现肝癌的治疗。

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来源期刊

Macromolecular Research 工程技术-高分子科学

CiteScore

4.70

自引率

8.30%

发文量

100

审稿时长

1.3 months

期刊介绍： Original research on all aspects of polymer science, engineering and technology, including nanotechnology Presents original research articles on all aspects of polymer science, engineering and technology Coverage extends to such topics as nanotechnology, biotechnology and information technology The English-language journal of the Polymer Society of Korea Macromolecular Research is a scientific journal published monthly by the Polymer Society of Korea. Macromolecular Research publishes original researches on all aspects of polymer science, engineering, and technology as well as new emerging technologies using polymeric materials including nanotechnology, biotechnology, and information technology in forms of Articles, Communications, Notes, Reviews, and Feature articles.