Synergistic delivery of 5-FU and thymoquinone via biogenic CaCO₃ NPs in hyperglycemia-linked colorectal cancer cell.

IF 3.4 Q2 PHARMACOLOGY & PHARMACY

Therapeutic delivery Pub Date : 2025-11-01 Epub Date: 2025-12-05 DOI:10.1080/20415990.2025.2594305

Prethiba K Ganasan, Norsharina Ismail, Ahmad Faizal Abdull Razis, Md Zuki Bin Abu Bakar, Kim Wei Chan

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引用次数: 0

Abstract

Aim: This study evaluated two novel combination therapies using 5-Fluorouracil (5-FU), Thymoquinone (TQ), and cockle shell - derived calcium carbonate nanoparticles (CaCO₃ NPs) against HT-29 colorectal cancer (CRC) cells under hyperglycemic conditions.

Methods: 5-FU and TQ were successfully encapsulated into CaCO₃ NPs through encapsulation at various drug-to-nanoparticle ratios. Physicochemical characterization was performed to confirm the morphology, and particle stability. Drug release studies assessed pH-responsive behavior, while biocompatibility was evaluated on NIH/3T3 cells. Cytotoxicity and cell cycle analyses were conducted on HT-29 cells under glycemic and hyperglycemic conditions.

Results: High encapsulation efficiency was achieved at a 1:5 drug-to-nanoparticle ratio while maintaining the aragonite structure and stable physicochemical properties. The nanoformulations exhibited pH-sensitive drug release with enhanced release at acidic pH (4.8), simulating the tumor microenvironment. Improved biocompatibility and reduced toxicity were observed in normal NIH/3T3 cells compared to free drugs. Both 5-FU:TQ-CaCO₃ NPs and 5-FU-CaCO₃ NPs:TQ combinations significantly inhibited HT-29 proliferation and induced G1 cell cycle arrest, especially under hyperglycemic conditions. Combination index analysis confirmed synergistic effects of both treatments.

Conclusion: The findings suggest the potential therapeutic efficacy of 5-FU:TQ-CaCO₃ NPs and 5-FU-CaCO₃ NPs:TQ in treating CRC associated with hyperglycemia and demonstrate the capability of biogenic CaCO₃ NPs to effectively deliver chemotherapeutic agents of different polarity with minimal toxicity.

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5-FU和百里醌通过生物源性CaCO3 NPs在高血糖相关结直肠癌细胞中的协同递送。

目的：本研究评估了5-氟尿嘧啶（5-FU）、百里醌（TQ）和贝壳衍生的碳酸钙纳米颗粒（CaCO3 NPs）对高血糖状态下HT-29结直肠癌（CRC）细胞的两种新型联合疗法。方法：将5-FU和TQ以不同的药纳米比包封至CaCO3 NPs中。进行了物理化学表征，以确定形貌和颗粒稳定性。药物释放研究评估ph反应行为，同时评估NIH/3T3细胞的生物相容性。在血糖升高和高血糖状态下对HT-29细胞进行细胞毒性和细胞周期分析。结果：以1:5的药纳米比包封，在保持文石结构和稳定理化性质的同时，获得了较高的包封效率。纳米制剂表现出pH敏感的药物释放，在酸性pH（4.8）下释放增强，模拟肿瘤微环境。与游离药物相比，正常NIH/3T3细胞的生物相容性得到改善，毒性降低。5-FU:TQ- caco3 NPs和5-FU- caco3 NPs:TQ联合用药均能显著抑制HT-29增殖并诱导G1细胞周期阻滞，尤其是在高血糖状态下。联合指标分析证实了两种治疗的协同效应。结论：研究结果提示5-FU:TQ-CaCO3 NPs和5-FU-CaCO3 NPs:TQ治疗结直肠癌合并高血糖的潜在疗效，并证明生物源性CaCO3 NPs能够有效递送不同极性的化疗药物，毒性最小。

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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来源期刊

Therapeutic delivery PHARMACOLOGY & PHARMACY-

CiteScore

5.50

自引率

0.00%

发文量

期刊介绍： Delivering therapeutics in a way that is right for the patient - safe, painless, reliable, targeted, efficient and cost effective - is the fundamental aim of scientists working in this area. Correspondingly, this evolving field has already yielded a diversity of delivery methods, including injectors, controlled release formulations, drug eluting implants and transdermal patches. Rapid technological advances and the desire to improve the efficacy and safety profile of existing medications by specific targeting to the site of action, combined with the drive to improve patient compliance, continue to fuel rapid research progress. Furthermore, the emergence of cell-based therapeutics and biopharmaceuticals such as proteins, peptides and nucleotides presents scientists with new and exciting challenges for the application of therapeutic delivery science and technology. Successful delivery strategies increasingly rely upon collaboration across a diversity of fields, including biology, chemistry, pharmacology, nanotechnology, physiology, materials science and engineering. Therapeutic Delivery recognizes the importance of this diverse research platform and encourages the publication of articles that reflect the highly interdisciplinary nature of the field. In a highly competitive industry, Therapeutic Delivery provides the busy researcher with a forum for the rapid publication of original research and critical reviews of all the latest relevant and significant developments, and focuses on how the technological, pharmacological, clinical and physiological aspects come together to successfully deliver modern therapeutics to patients. The journal delivers this essential information in concise, at-a-glance article formats that are readily accessible to the full spectrum of therapeutic delivery researchers.