In a recent study published in the Nutrients Journal, researchers comprehensively evaluated all nanotechnology-based approaches used to improve the therapeutic effectiveness of polyphenols against cancer.
Study: Recent Progress in Nanotechnology Improving the Therapeutic Potential of Polyphenols for Cancer. Image Credit: metamorworks/Shutterstock.com
The study summarized the recent advancements in developing nano-carried polyphenols with the potential for cancer therapy based on in vitro study results and preclinical trial data.
Additionally, the researchers addressed the use of polyphenol co-delivery systems, which decrease the adverse side effects of cancer treatment. Finally, they described future trends in polyphenol-loaded nanotechnology-based delivery systems for cancer treatment and their outlook for clinical research.
Polyphenols are bioactive agents present in many plants, fruits, and vegetables. Studies have highlighted that some polyphenols, such as curcumin, epigallocatechin-3-gallate (EGCG), quercetin, and resveratrol, have antiproliferative activity, essential to fight cancerous cells.
These polyphenolic compounds also have antioxidant properties and pro-oxidant, anti-angiogenic, and anti-metastatic effects.
Despite vast inherent potential against cancer, low solubility and poor bioavailability of polyphenols hamper their gastrointestinal (GI) absorption. In this regard, scientists have proposed using nanoencapsulation in delivery systems to improve the effectiveness of polyphenols.
About the study
In the present study, researchers described four main classes of nanocarriers/nanomaterials, polymeric, lipid-based, inorganic, and carbon-based. Many in vitro studies and animal preclinical tests have already elucidated in vivo anticancer properties of these materials.
Regardless of type, all these materials confer protection to polyphenols against the hostile environment of the human digestive system, thus, facilitating a controlled and targeted delivery to the target tissue of a cancer patient.
More importantly, they interfere at a specific stage of the carcinogenic process to inhibit cell proliferation and induce apoptosis in cancerous cells.
The anticancer potential of four different polyphenols: Curcumin, EGCG, Quercetin, and Resveratrol
Found in Curcuma longa L. (turmeric), curcumin has remarkable antitumor properties evidenced in various studies. Kazemi-Lomedasht et al. showed the anticancer effects of curcumin against T47D breast cancer cells. Its extract (concentration 22 μM) increased the inhibition of the telomerase gene expression in the T47D cell line and reduced cell viability by 50% in 48 hours.
In mice, researchers fed turmeric extract at a dosage of 500 mg/kg per day by oral gavage for seven weeks. It decreased the expression levels of several cytokines, including interleukin (IL)-1β, and IL-6, which suppressed the tumorigenesis induced by azoxymethane–dextran sodium sulfate (AOM-DSS). It also decreased the number and size of colorectal tumors.
EGCG, found in green tea (Camellia sinensis), suppressed the proliferation of H1299 lung cancer cells in concentrations >20 μM in a study by Chen et al. (2020). Its LEGCG derivate showed cell apoptosis rates of 8.63%, 12.78%, 25.62%, and 58.51% at concentrations zero, 10, 20, and 40 μg/mL, respectively.
Resveratrol, found in grapes, berries, and peanuts, showed a remarkable decrease in cell viability for A549 and H1299 lung cancer cell lines at concentrations of 50 μM and 25 μM, respectively, after 24 hours in a study by Liang et al. (2023).
It disturbed the lung cancer cellular homeostasis by destroying the cellular pool of antioxidants often active in cancer to increase the reactive oxygen species (ROS) production.
Finally, the authors described that several studies have evaluated different concentrations of quercetin and found that this unique compound has a high potential to fight different types of cancers, including breast, colorectal, cervical, and lung.
Recently, Hashemzaei et al. (2017) evaluated the effect of quercetin in preclinical studies in mice. The treatment comprised 50, 100, and 200 mg/kg concentrations of quercetin and 5% dextrose for the control group. After 18 days, this treatment shrunk breast tumor sizes and improved survival rates in the group treated with a 200 mg/kg dosage.
Further, the researchers explored all functional nanomaterials currently used for encapsulating polyphenols for cancer based on their stability, loading capacity, release, and targeting.
They observed that polymeric nanoparticles, e.g., micelles and nanospheres exhibited a higher self-assembling capacity under certain pH conditions, more biodegradability, and persistent drug delivery.
Likewise, they noted that lipid-based nanomaterials, such as niosomes and liposomes, showed potential as promising nanocarriers due to their non-toxic nature and efficient cell penetration potential that facilitated targeted polyphenol delivery.
However, inorganic nanoparticles, e.g., gold nanoparticles, quantum dots, carbon-based nanomaterials, such as graphene and its derivatives, and fullerene, showed limited potential as nanocarriers due to toxicity issues and a low polyphenol loading efficacy.
To summarize, the researchers identified that clinical applications of polyphenol delivery systems for cancer therapy are wider than perceived before. The ability to selectively target cancer cells, fewer side effects, and increased therapeutic efficacy might help devise efficient and personalized cancer therapies in the future.
However, improving these nanotechnology-based delivery systems concerning clinical efficacy is paramount.
More importantly, there is a need for additional studies to enlarge the knowledge base of polyphenol-loaded nanotechnology-based delivery systems, with a razor-sharp focus on their pharmacokinetics, bioavailability & compatibility, toxicity, mechanisms of action, and establish their in vivo efficacy.