Natural Product-Based Nanomicelles: Properties, Fabrication Strategies, and Therapeutic Applications in Diseases

Many bioactive natural products suffer from poor water solubility, rapid metabolism, and low bioavailability, which severely limit their clinical application. Natural product‑based nanomicelles (NSNs), which integrate the delivery functions of nanocarriers with the intrinsic therapeutic activities of the materials themselves, offer a promising solution to this dilemma. NSNs are self‑assembled nanoscale delivery systems constructed from natural small molecules, natural polymers, and their derivatives. This review provides a systematic overview of NSNs. We first summarize their main fabrication strategies, including nanoprecipitation, dialysis, thin‑film hydration, chemical conjugation, and electrostatic interaction, and compare the biological characteristics of NSNs with those of synthetic polymer micelles. The core advantages of NSNs include excellent biocompatibility, intrinsic lesion‑targeting capability, and drug‑excipient synergy. Subsequently, we detail the mechanisms and therapeutic applications of NSNs in six major disease areas: anti‑infection, oncology, inflammation and autoimmune diseases, metabolic diseases, fibrotic diseases, and nervous system disorders. A cross‑disease analysis reveals that modulation of oxidative stress is a common core mechanism underlying the therapeutic benefits of NSNs. Finally, we critically discuss the major barriers to clinical translation, such as batch‑to‑batch variability of natural materials and good manufacturing practice compliance, and propose future directions including mechanism‑driven rational design, theranostics, and manufacturing scalability.