Progress of anti-tumor research on natural products combined with doxorubicin.

Cancer represents a major global public health challenge, with its incidence and mortality rates increasing annually. Doxorubicin (DOX) is a commonly used chemotherapeutic agent. Despite its marked antitumor efficacy, the clinical application of DOX is limited by drug resistance and cumulative toxicity. Numerous natural products have garnered significant attention owing to their favorable antitumor, antioxidant, anti-inflammatory, and anti-apoptotic properties, and are increasingly being developed as adjuvant agents in combination therapy with DOX. The co-administration of natural products with DOX has emerged as a promising strategy to enhance therapeutic outcomes while mitigating adverse effects. However, this combination approach is constrained by poor drug solubility and disparate pharmacokinetic profiles. The advent of multifunctional nanodelivery systems has improved drug bioavailability and tumor targeting, thereby laying the groundwork for synergistic interactions between natural products and DOX. This review systematically summarizes the antitumor mechanisms and toxic side effects of DOX, elucidates the mechanisms of action and structure-activity relationships of certain natural products serving as DOX sensitizers and protective agents, and highlights recent advances in nano-platform-based co-delivery strategies, offering valuable insights for future cancer therapeutics.