Posted by Aspirin, a non-steroidal anti-inflammatory drug (NSAID), has garnered significant attention for its anti-cancer potential. This review [1] explores the pharmacological properties, chemical dynamics, and evolving therapeutic applications of aspirin, with an emphasis on its integration into advanced cancer therapies. Aspirin demonstrates broad-spectrum efficacy across diverse cancer types by modulating signaling pathways such as COX-dependent and COX-independent mechanisms, including Wnt, NF-κB, β-catenin/TCF, and IL-6/STAT3. Recent advancements highlight the role of nanotechnology in enhancing aspirin’s targeted delivery, therapeutic effectiveness, and patient outcomes. Nanoparticle-based formulations, including liposomes, solid lipid nanoparticles, and mesoporous silica nanoparticles, offer improved solubility, stability, and bioavailability, enabling controlled drug release and tumor-specific targeting. These innovations reduce systemic toxicity and enhance therapeutic effects, paving the way for aspirin’s integration into personalized cancer treatments. Ongoing clinical studies reinforce its safety profile, underscoring aspirin’s role in cancer pharmacotherapy. This review calls for continued research into aspirin’s repurposing in combination therapies and novel delivery systems to maximize its therapeutic potential.
While traditionally used for pain relief, fever reduction, and cardiovascular protection, recent research has highlighted aspirin’s promising role in cancer prevention and treatment. Long-term studies have shown that regular aspirin use can reduce the risk of cancers, particularly colorectal cancer, and is now being investigated for its potential to inhibit tumor growth, metastasis, and inflammation in various cancer types. The anticancer effects of aspirin are largely attributed to its inhibition of cyclooxygenase enzymes (COX-1 and COX-2), particularly COX-2, which is often overexpressed in tumors. COX-2 mediates the production of pro-inflammatory prostaglandins, which promote tumor growth, angiogenesis, and metastasis. By inhibiting COX-2, aspirin not only reduces inflammation but also disrupts tumor-promoting signaling pathways, including those involved in DNA repair, apoptosis, and cell cycle regulation. Additionally, aspirin reflects antiplatelet effect by preventing thrombus formation in cardiovascular conditions. It demonstrates this effect by inhibition of thromboxane A2 synthesis in the platelets. In recent years, a growing interest regarding the practical utility of aspirin as primary and secondary prevention of cancer has boosted its research in anti-cancer strategies. The anti-cancer potential of aspirin is a consequence of aspirin-mediated inhibition of various signaling pathways, including β-catenin/TCF pathway and the IL-6/STAT3 pathway. Clinical evidence supports aspirin’s role in lowering cancer incidence, especially in the colorectal, breast, and gastric cancers. Furthermore, aspirin has shown potential in enhancing the efficacy of chemotherapeutic agents, suggesting its utility as an adjunct therapy in cancer treatment.
In recent years, however, there has been growing interest in the development of innovative formulations and delivery systems to enhance aspirin’s anticancer efficacy and minimize its adverse effects. One of the most promising strategies is the integration of nanotechnology, which offers a means to overcome many of the limitations associated with conventional aspirin therapy. Nanotechnology allows for the design of aspirin-loaded nanocarriers, such as liposomes, solid lipid nanoparticles (SLNs), mesoporous silica nanoparticles (MSNs) and dendrimers, which significantly improve the drug’s solubility, stability, and bioavailability.
CD complexation, although not mentoned in the article, was studied first almost 50 years ago and the 1:1 molar ratio of BCD:Aspirin was established [2], while ACD forms 2:1 host:guest complex [3]. The complex with BCD was formed simply by grinding the two components, while that with ACD was prepared by freeze drying. BCD, however, accelerated the hydrolysis of aspirin both in solid and alkaline liquid state [4], but retarded it in acidic conditions. Although ionization of the drug also reduced the degree of complexation, complexation with ionized drug resulted in much larger total solubilization [5]. Recent studies showed that gamma-cyclodextrin (GCD) metal organic framework (MOF)-encapsulated aspirin enables the treatment of the inflammatory environment within the thrombus, enhancing the antiplatelet aggregation effects and promoting cooperative thrombolysis therapy [6].
Reference:
[1] Laila UE, Zhao ZL, Lui H, Xu ZX. Aspirin in Cancer Therapy: Pharmacology and Nanotechnology Advances. Int J Nanomedicine. 2025;20:2327-2365. https://doi.org/10.2147/IJN.S505636
[2] Nakai Y, Nakajima S, Yamamoto K, Terada K, Konno T. Effects of grinding on the physical and chemical properties of crystalline medicinals with microcrystalline cellulose. IV. Comparison of the IR spectra of medicinals in the solid state and in solution. Chem Pharm Bull (Tokyo). 1980 Feb;28(2):652-6. doi: https://doi.org/10.1248/cpb.28.652.
[3] Toshio Oguchi, Makoto Okada, Etsuo Yonemochi, Keiji Yamamoto, Yoshinobu Nakai,
Freeze-drying of drug-additive binary systems III. Crystallization of α-cyclodextrin inclusion complex in freezing process. International Journal of Pharmaceutics 1990; 61, 27-34.
https://doi.org/10.1016/0378-5173(90)90040-B.
[4] P Jones, G D Parr, D Jackson, Computer Graphics as an AID for Predicting Drug Molecule Stability in a Cyclodextrin Inclusion Complex, Journal of Pharmacy and Pharmacology, Volume 38, Issue Supplement_12, December 1986, Page 94P, https://doi.org/10.1111/j.2042-7158.1986.tb14323.x
[5] Loftsson, T., Olafsdottir, B. J., Frioriksdottir, H., Jonsdottir, S., & Fridriksdóttir, H. (1993). Cyclodextrin complexation of NSAIDs: Physicochemical characteristics: physicochemical characteristics. European Journal of Pharmaceutical Sciences, 1(2), 95-101. https://doi.org/10.1016/0928-0987(93)90023-4
[6] C Yuan, Y Ye, E Hu, R Xie, B Lu, K Yu, W Ding, W Wang, G Lan, F Lu (2024) Thrombotic microenvironment responsive crosslinking cyclodextrin metal-organic framework nanocarriers for precise targeting and thrombolysis. Carbohydrate Polymers 334, 122058.
https://doi.org/10.1016/j.carbpol.2024.122058.