Colon cancer is the third most common cancer worldwide, with high mortality. Adverse side effects and chemoresistance of the first-line chemotherapy 5-fluorouracil (5-FU) have promoted the widespread use of combination therapies. Thymoquinone (TQ) is a natural compound with potent antioxidant activity. Loading antioxidants into nano delivery systems has been a major advance in enhancing their bioavailability to improve clinical application. Hence, this study aimed to prepare the optimal TQ-loaded calcium carbonate nanoparticles (TQ-CaCO₃ NPs) and investigate their therapeutic potential and underlying molecular mechanisms of TQ-CaCO₃ NPs in combination with 5-FU against colon cancer. Firstly, we developed purely aragonite CaCO₃ NPs with a facile mechanical ball-milling method. The pH-sensitive and biocompatible TQ-CaCO₃ NPs with sustained release properties were prepared using the optimal synthesized method (a high-speed homogenizer). The in vitro study revealed that the combination of TQ-CaCO₃ NPs (15 μM) and 5-FU (7.5 μM) inhibited CT26 cell proliferation and migration, induced cell apoptosis and cell cycle arrest in the G₀/G₁ phase, and suppressed the CT26 spheroid growth, exhibiting a synergistic effect. Finally, network pharmacology and molecular docking results indicated the potential targets and crucial signaling pathways of TQ-CaCO₃ NPs in combination with 5-FU against colon cancer. Therefore, TQ-CaCO₃ NPs combined with 5-FU could enhance the anti-colon cancer effects of 5-FU with broader therapeutic targets, warranting further application for colon cancer treatment.

Drimenol, a phytochemical with a distinct odor is found in edible aromatic plants, such as Polygonum minus (known as kesum in Malaysia) and Drimys winteri. Recently, drimenol has received increasing attention owing to its diverse biological activities. This review offers the first extensive overview of drimenol, covering its sources, bioactivities, and derivatives. Notably, drimenol possesses a wide spectrum of biological activities, including antifungal, antibacterial, anti-insect, antiparasitic, cytotoxic, anticancer, and antioxidant effects. Moreover, some mechanisms of its activities, such as its antifungal effects against human mycoses and anticancer activities, have been investigated. However, there are still several crucial issues in the research on drimenol, such as the lack of experimental understanding of its pharmacokinetics, bioavailability, and toxicity. By synthesizing current research findings, this review aims to present a holistic understanding of drimenol, paving the way for future studies and its potential utilization in diverse fields.

Given the need for novel and effective therapies for colon cancer, this study aimed to investigate the effects of 5-fluorouracil-loaded calcium carbonate nanoparticles (5FU-CaCO₃np) combined with thymoquinone (TQ) against colon cancer. A shaking incubator and a high-speed homogenizer were used to prepare the optimal 5FU-CaCO₃np, with characterizations of physicochemical properties, in vitro drug release profile, and biocompatibility. In vitro experiments and molecular docking were employed to evaluate the therapeutic potential of the combination for colon cancer treatment. Study results revealed that 5FU-CaCO₃np with a size of approximately 130 nm was synthesized using the high-speed homogenizer. Its favorable biocompatibility, pH sensitivity, and sustained release properties facilitated reduced toxic side effects of 5-FU on NIH3T3 normal cells and enhanced inhibitory effects on CT26 colon cancer cells. The combination of 5FU-CaCO₃np (1.875 μM) and TQ (30 μM) showed significantly superior anti-colon cancer effects to 5FU-CaCO₃np alone in terms of cell proliferation and migration inhibition, cell apoptosis induction, and spheroid growth suppression in CT26 cells (p < 0.05), with strong interactions between the drugs and targets (E-cadherin, Bcl-2, PCNA, and MMP-2). These results provide evidence for 5FU-CaCO₃np as a novel regimen against colon cancer. Combining 5FU-CaCO₃np and TQ may offer a new perspective for colon cancer therapy.

Calcium carbonate nanoparticles (CaCO₃ NPs) have garnered broad attention as promising nanocarriers for cancer therapy owing to their biocompatibility, pH sensitivity, ease of synthesis, and tunable surface properties. These NPs remain stable under physiological conditions but rapidly dissolve in the acidic tumor microenvironment, enabling controlled drug release. Various synthesis methods, including solution precipitation, microemulsion, gas diffusion, flame synthesis, biomineralization, and mechanical ball milling techniques, have been explored to optimize their physicochemical properties. CaCO₃ NPs can be functionalized with targeting ligands, polymers, and biomolecules to enhance therapeutic efficacy and selectivity. Their ability to co-deliver multiple drugs and achieve synergistic therapeutic effects further enhances their potential in cancer treatment. This review uniquely integrates synthesis strategies, drug delivery mechanisms, and clinical challenges, offering systematic insights to bridge laboratory advances with clinical translation. Moreover, critical challenges such as stability, reproducibility, and potential safety concerns are discussed, alongside strategies to overcome these limitations. Despite their promise, further research is needed to refine synthesis techniques, assess long-term safety, and improve clinical translation. By addressing these challenges, CaCO₃ NPs could become a valuable tool for targeted cancer therapy, offering enhanced treatment efficacy with reduced side effects.