Delivery of Natural Small Molecules Through Nanocarriers for Cancer Treatment

ABSTRACT Cancer is a formidable adversary, accounting for the second highest number of fatalities worldwide. A multitude of studies have indicated that naturally sourced small‐molecule compounds, owing to their low toxicity and multi‐target capabilities, significantly aid in the fight against tumorigenesis. However, natural small molecules have certain limitations, such as poor water solubility and permeability. These limitations curtail their clinical potency and result in lower bioavailability within the human body. To address these limitations, nano‐encapsulation techniques have emerged as a promising strategy to enhance the solubility, stability, and delivery of these natural compounds. For instance, in several preclinical studies, encapsulating resveratrol in liposomal nanocarriers increased its solubility by up to 50‐fold and enhanced its bioavailability by three to five times. This work is based on the reports published from 1999 to 2024 in PubMed and ISI Web of Science databases. This review examines the anticancer mechanisms of key natural small molecules, including polyphenols, alkaloids, and terpenes, and discusses how their incorporation into nanocarrier systems improves their efficacy. Additionally, this analysis provides a comprehensive overview of how nanotechnology can overcome the pharmacokinetic and bioavailability limitations of natural compounds, offering a foundation for future advancements in cancer treatment.