Colon-Targeted Sustained-Release Combinatorial 5-Fluorouracil and Quercetin poly(lactic-co-glycolic) Acid (PLGA) Nanoparticles Show Enhanced Apoptosis and Minimal Tumor Drug Resistance for Their Potential Use in Colon Cancer

IF 4.9 Q1 CHEMISTRY, MEDICINAL ACS Pharmacology and Translational Science Pub Date : 2024-08-20 DOI:10.1021/acsptsci.4c0046210.1021/acsptsci.4c00462

Ahmed Kh. Abosalha, Paromita Islam, Jacqueline L. Boyajian, Rahul Thareja, Sabrina Schaly, Amal Kassab, Stephanie Makhlouf, Sarah Alali and Satya Prakash*,

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Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide, acting as a significant public health problem. 5-Fluorouracil (5-FU) is a key chemotherapy for various types of cancer, due to its broad anticancer activity. However, the emergence of drug resistance is a considerable limitation in the clinical application of 5-FU. Quercetin (QC) is proposed as an adjuvant therapy to minimize drug resistance to chemotherapeutics and enhance their pharmacological efficacy. The oral delivery of 5-FU and QC is challenged by poor aqueous solubility of QC and poor cellular permeability of 5-FU. To solve this issue, novel polylactide-co-glycolide (PLGA) combinatorial nanoparticles loading 5-FU and QC were prepared to deliver them directly to the colon. These sustained-release combinatorial nanoparticles recorded a significant decrease in cancer cell proliferation, C-reactive protein (CRP) level, and Interleukin-8 (IL-8) expression by 30.08%, 40.7%, and 46.6%, respectively. The results revealed that this combination therapy may offer a new strategy for the targeted delivery of chemotherapeutics to the colon.

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结肠靶向缓释 5-氟尿嘧啶和槲皮素聚乳酸-共聚乙醇酸 (PLGA) 组合纳米粒子显示出更强的细胞凋亡能力和最小的肿瘤耐药性，有望用于结肠癌治疗

结直肠癌（CRC）是全球第三大常见癌症，是一个重大的公共卫生问题。5-氟尿嘧啶（5-FU）具有广泛的抗癌活性，是治疗各种癌症的主要化疗药物。然而，耐药性的出现极大地限制了 5-FU 的临床应用。槲皮素（QC）被建议作为一种辅助疗法，以最大限度地减少化疗药物的耐药性，并提高其药效。由于 QC 的水溶性差和 5-FU 的细胞渗透性差，5-FU 和 QC 的口服给药面临挑战。为解决这一问题，研究人员制备了负载 5-FU 和 QC 的新型聚乳酸-聚乙二醇（PLGA）组合纳米颗粒，将它们直接输送到结肠。这些缓释组合纳米粒子显著降低了癌细胞增殖、C反应蛋白（CRP）水平和白细胞介素-8（IL-8）表达，降幅分别为30.08%、40.7%和46.6%。研究结果表明，这种联合疗法可为向结肠靶向输送化疗药物提供一种新策略。

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来源期刊

ACS Pharmacology and Translational Science Medicine-Pharmacology (medical)

CiteScore

10.00

自引率

3.30%

发文量

133

期刊介绍： ACS Pharmacology & Translational Science publishes high quality, innovative, and impactful research across the broad spectrum of biological sciences, covering basic and molecular sciences through to translational preclinical studies. Clinical studies that address novel mechanisms of action, and methodological papers that provide innovation, and advance translation, will also be considered. We give priority to studies that fully integrate basic pharmacological and/or biochemical findings into physiological processes that have translational potential in a broad range of biomedical disciplines. Therefore, studies that employ a complementary blend of in vitro and in vivo systems are of particular interest to the journal. Nonetheless, all innovative and impactful research that has an articulated translational relevance will be considered. ACS Pharmacology & Translational Science does not publish research on biological extracts that have unknown concentration or unknown chemical composition. Authors are encouraged to use the pre-submission inquiry mechanism to ensure relevance and appropriateness of research.