Receptor‐Targeted Niosomal Nanocarriers: Advances, Challenges, and Opportunities in Natural Compound Delivery for Cancer Therapy

ABSTRACT Receptor‐induced targeting of a niosomal delivery system may be a good tool for targeted and safe delivery of bioactive natural compounds to the tumor site with reduced systemic toxicity. Natural phytochemicals have strong therapeutic effects; however, their clinical applications are greatly hampered due to poor solubility, rapid metabolism, and low bioavailability. This review systematically reviews the state‐of‐the‐art surface‐engineered niosomes for phytochemical oncology, with a particular focus on ligand‐mediated delivery to overexpressed tumor receptors. We critically review advanced nanofabrication methodologies and precise covalent conjugation chemistries for targeted cellular internalization, as well as improved combinatorial pharmacodynamic efficacies. By combining preclinical evidence from diverse receptor–ligand systems, this review recapitulates the critical mechanistic information necessary to overcome multidrug resistance (MDR) and improve tumor specificity. Key drivers influencing mechanism‐based hypotheses of target cell uptake include ligand identity, conjugation chemistry, ligand density and orientation, bilayer composition, and processing conditions; each of which contributes to optimal receptor binding, endocytic internalization/trafficking dynamics, and ultimately therapeutic index. Last but not least, we suggest a translational roadmap while identifying key challenges of industrial scale‐up, functional ligand stability, and the integration of Quality by Design (QbD) principles that would make receptor‐targeted niosomes an enabling technology for next‐generation personalized nanomedicine.