Clinical Translation Potential of Surface-Modified Proniosomes in Systemic Cancer Therapeutics

Abstract: Proniosomes are anhydrous, non-ionic surfactant precursors that rehydrate into bilayered niosomes, addressing long-standing challenges in systemic cancer drug delivery. We systematically reviewed oncology-targeted proniosome publications, comparing drug loading, stability, release, and pharmacokinetics with liposomes, polymeric nanoparticles, micelles, and solid-lipid nanoparticles. We assessed design determinants (surfactant composition, cholesterol ratio, charge inducers), surface modifications (PEGylation, ligand conjugation, pH- or thermoresponsive groups), and conducted a SWOT analysis. Proniosomes demonstrated high physicochemical stability, robust encapsulation, and controlled release, supporting hydrophilic, hydrophobic, and macromolecular payloads. Self-assembly and vesicle characteristics were controlled by surfactant/cholesterol/charge composition. Surface modification prolonged circulation halflife, augmented tumour accumulation and intracellular delivery, and minimized off-targeting and immunogenicity. Functional developments allowed systemic delivery of chemotherapeutics and biologics, co-delivery with nucleic acids (siRNA, CRISPR-Cas9), and theranostic integration with imaging agents. Compared with peer platforms, proniosomes equalled or surpassed drug loading, stability, and systemic bioavailability, and the dry format minimized manufacturing and scale-up. Modularity of the platform facilitates targeted, multi-functional regimens and individualized dosing, providing a pragmatic path to precision oncology. Issues remaining are regulatory routes, batch reproducibility, and industrial scale-up.