Multifunctional PAMAM Dendrimers Carrying SAHA, 5-FU, and a Therapeutic Gene for Targeted Co-Delivery Toward Colorectal Cancer Cells

IF 3.2 3区生物学 Q2 BIOCHEMICAL RESEARCH METHODS Biotechnology Journal Pub Date : 2024-11-17 DOI:10.1002/biot.202400362

Bünyamin Bulkurcuoğlu, Mustafa Ulvi Gürbüz, Silvia Tyciakova, Kristina Pavlov, Nikoleta Mojzesova, Miroslava Matuskova, Metin Tülü, Şebnem Erçelen

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Abstract

A promising approach to treat colorectal cancer (CRC) involves combining chemotherapy, epigenetics, and gene therapy to combat drug resistance. Multifunctional nanocarriers have emerged as a valuable tool for targeted CRC therapy. By delivering multiple treatments directly to cancer cells, these nanocarriers offer the potential for improved outcomes and reduced side effects. PAMAM-based dendrimers were functionalized with a unique combination of folic acid, 5-FU, SAHA, and plasmid DNA pCIneoGFP for targeted delivery to CRC cells. Biophysical characterizations of therapeutic loaded dendrimers and their complexes with pCIneoGFP were performed by: dynamic light scattering, fluorescence spectroscopy, and gel electrophoresis. Further, cellular analyses of dendriplexes demonstrated high transfection efficiency and anticancer activity on HCT 116 and HT-29 cell lines. We have successfully developed a multifunctional nanocarrier platform based on PAMAM dendrimers, offering a promising tool for targeted combination therapy of CRC.

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携带 SAHA、5-FU 和治疗基因的多功能 PAMAM 树枝状聚合物，可对结直肠癌细胞进行靶向联合给药。

治疗结直肠癌（CRC）的一种前景广阔的方法是结合化疗、表观遗传学和基因疗法来对抗耐药性。多功能纳米载体已成为 CRC 靶向治疗的重要工具。通过直接向癌细胞输送多种治疗药物，这些纳米载体有望提高疗效并减少副作用。我们用叶酸、5-FU、SAHA 和质粒 DNA pCIneoGFP 的独特组合对基于 PAMAM 的树枝状聚合物进行了功能化处理，以实现对 CRC 细胞的靶向递送。研究人员通过动态光散射、荧光光谱和凝胶电泳对载入治疗药物的树枝状聚合物及其与 pCIneoGFP 的复合物进行了生物物理表征。此外，树枝状复合物的细胞分析表明，它对 HCT 116 和 HT-29 细胞系具有很高的转染效率和抗癌活性。我们成功开发了一种基于 PAMAM 树枝状聚合物的多功能纳米载体平台，为靶向联合治疗 CRC 提供了一种前景广阔的工具。

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来源期刊

Biotechnology Journal Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

8.90

自引率

2.10%

发文量

123

审稿时长

1.5 months

期刊介绍： Biotechnology Journal (2019 Journal Citation Reports: 3.543) is fully comprehensive in its scope and publishes strictly peer-reviewed papers covering novel aspects and methods in all areas of biotechnology. Some issues are devoted to a special topic, providing the latest information on the most crucial areas of research and technological advances. In addition to these special issues, the journal welcomes unsolicited submissions for primary research articles, such as Research Articles, Rapid Communications and Biotech Methods. BTJ also welcomes proposals of Review Articles - please send in a brief outline of the article and the senior author''s CV to the editorial office. BTJ promotes a special emphasis on: Systems Biotechnology Synthetic Biology and Metabolic Engineering Nanobiotechnology and Biomaterials Tissue engineering, Regenerative Medicine and Stem cells Gene Editing, Gene therapy and Immunotherapy Omics technologies Industrial Biotechnology, Biopharmaceuticals and Biocatalysis Bioprocess engineering and Downstream processing Plant Biotechnology Biosafety, Biotech Ethics, Science Communication Methods and Advances.