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双作用吉西他滨递送：用于靶向癌症治疗和抗菌防御的壳聚糖-磁铁矿-沸石胶囊

Dual-Action Gemcitabine Delivery: Chitosan-Magnetite-Zeolite Capsules for Targeted Cancer Therapy and Antibacterial Defense.

作者信息

Guarín-González Yuly Andrea, Cabello-Guzmán Gerardo, Reyes-Gasga José, Moreno-Navarro Yanko, Vergara-González Luis, Martin-Martín Antonia, López-Muñoz Rodrigo, Cárdenas-Triviño Galo, Barraza Luis F

机构信息

Laboratorio Térmico de Nano y Macromateriales, Edificio de Procesos Sustentables, Departamento de Ingeniería en Maderas, Universidad del Bío-Bío, Concepción 4081112, Chile.

Facultad de Ciencias, Departamento de Biología y Química, Universidad del Bío-Bío, Chillán 3780000, Chile.

出版信息

Gels. 2024 Oct 21;10(10):672. doi: 10.3390/gels10100672.

DOI:10.3390/gels10100672
PMID:39451325
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11507657/
Abstract

Cancer and infectious diseases are two of the world's major public health problems. Gemcitabine (GEM) is an effective chemotherapeutic agent against several types of cancer. In this study, we developed macrocapsules incorporating GEM into a chitosan matrix blended with magnetite and zeolite by ionic gelation. Physicochemical characterization was performed using HRTEM-ED, XRD, FESEM-EDS, FT-IR, TGA, encapsulation efficiency (%E.E.), and release profiles at pHs 7.4 and 5.0. Cell viability tests against A549 and H1299 cell lines, and microbiological properties against staphylococcal strains were performed. Our results revealed the successful production of hemispherical capsules with an average diameter of 1.22 mm, a rough surface, and characteristic FT-IR material interaction bands. The macrocapsules showed a high GEM encapsulation efficiency of over 86% and controlled release over 24 h. Cell viability assays revealed that similar cytotoxic effects to free GEM were achieved with a 45-fold lower GEM concentration, suggesting reduced dosing requirements and potentially fewer side effects. Additionally, the macrocapsules demonstrated potent antimicrobial activity, reducing growth by over 90%. These results highlight the macrocapsules dual role as a chemotherapeutic and antimicrobial agent, offering a promising strategy for treating lung cancer in patients at risk of infectious diseases or who are immunosuppressed.

摘要

癌症和传染病是世界上两大主要的公共卫生问题。吉西他滨（GEM）是一种针对多种癌症的有效化疗药物。在本研究中，我们通过离子凝胶法制备了将GEM包裹在与磁铁矿和沸石混合的壳聚糖基质中的大胶囊。使用高分辨率透射电子显微镜-能谱仪（HRTEM-ED）、X射线衍射仪（XRD）、场发射扫描电子显微镜-能谱仪（FESEM-EDS）、傅里叶变换红外光谱仪（FT-IR）、热重分析仪（TGA）、包封率（%E.E.）以及在pH值为7.4和5.0时的释放曲线进行了物理化学表征。针对A549和H1299细胞系进行了细胞活力测试，并针对葡萄球菌菌株进行了微生物学特性测试。我们的结果表明成功制备出了平均直径为1.22毫米、表面粗糙且具有特征性FT-IR材料相互作用带的半球形胶囊。大胶囊显示出超过86% 的高GEM包封率以及24小时的控释效果。细胞活力测定表明，使用低45倍的GEM浓度可实现与游离GEM相似的细胞毒性作用，这表明给药需求减少且潜在副作用可能更少。此外，大胶囊表现出强大的抗菌活性，使细菌生长减少超过90%。这些结果突出了大胶囊作为化疗药物和抗菌剂的双重作用，为治疗有传染病风险或免疫抑制的肺癌患者提供了一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/869e50f312d3/gels-10-00672-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/aeb0f98e44e5/gels-10-00672-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/d145ee2408b4/gels-10-00672-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/2c3acc5b1f4a/gels-10-00672-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/d392e8c9aa64/gels-10-00672-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/8f8a8a570c3e/gels-10-00672-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/59efabadfd8a/gels-10-00672-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/e05de68b81ff/gels-10-00672-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/869e50f312d3/gels-10-00672-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/aeb0f98e44e5/gels-10-00672-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/d145ee2408b4/gels-10-00672-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/b3d050783fe7/gels-10-00672-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/2c3acc5b1f4a/gels-10-00672-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/d392e8c9aa64/gels-10-00672-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/8f8a8a570c3e/gels-10-00672-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/59efabadfd8a/gels-10-00672-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/e05de68b81ff/gels-10-00672-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ad/11507657/869e50f312d3/gels-10-00672-g009.jpg

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本文引用的文献

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Reinforcement learning strategies in cancer chemotherapy treatments: A review.强化学习策略在癌症化疗治疗中的应用：综述。
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Chitosan - zeolite scaffold as a potential biomaterial in the controlled release of drugs for osteoporosis.壳聚糖-沸石支架作为一种用于骨质疏松症药物控释的潜在生物材料。
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The past, present, and future of chemotherapy with a focus on individualization of drug dosing.
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Comparative analysis of three vs. four cycles of neoadjuvant gemcitabine and cisplatin for muscle invasive bladder cancer.比较新辅助吉西他滨和顺铂三联与四联方案治疗肌层浸润性膀胱癌。
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A novel chitosan oligosaccharide derivative: Synthesis, antioxidant and antibacterial properties.一种新型壳寡糖衍生物：合成、抗氧化和抗菌性能。
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may be a key factor regulating the chemosensitivity of pancreatic cancer to gemcitabine.可能是调节胰腺癌对吉西他滨化疗敏感性的关键因素。
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Engineering a folic acid-decorated ultrasmall gemcitabine nanocarrier for breast cancer therapy: Dual targeting of tumor cells and tumor-associated macrophages.工程化一种用于乳腺癌治疗的叶酸修饰的超小吉西他滨纳米载体：对肿瘤细胞和肿瘤相关巨噬细胞的双重靶向作用
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Emerging pro-drug and nano-drug strategies for gemcitabine-based cancer therapy.基于吉西他滨的癌症治疗的新兴前药和纳米药物策略。
Asian J Pharm Sci. 2022 Jan;17(1):35-52. doi: 10.1016/j.ajps.2021.06.001. Epub 2021 Jul 1.
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