Biosurfactant-amphiphilized hyaluronic acid: A dual self-assembly anticancer nanoconjugate and drug vector for synergistic chemotherapy

Abstract

Novel amphiphilic nanoconjugates of hyaluronic acid (HA), 50 kDa (HA50) and 100 kDa (HA100), and the lipopeptide biosurfactant surfactin (SF) were developed for potential anticancer applications. Physicochemical characterization indicated the formation of an ester conjugate (HA: SF molar ratio 1: 40) with the HA50-SF derivative exhibiting higher degree of substitution, hydrolytic stability, and surface activity. Self-assembly resulted in nanomicelles with smaller size and greater negative charge relative to SF micelles. Biological data demonstrated distinct anticancer activity of HA50-SF which displayed greater synergistic cytotoxicity and selectivity for MDA-MB 231 and MCF-7 breast cancer cells alongside greater modulation of apoptosis-related biomarkers leading to apoptosis. As bioactive vector for chemotherapeutic agents, the selected HA50-SF nanoconjugate efficiently (70 %) entrapped berberine (BER) producing a sustained release BER-HA50-SF synergistic anticancer nanoformulation. Lactoferrin (Lf) coating for dual HA/Lf targeting endowed Lf/BER-HA50-SF with significantly greater selectivity for both cell lines. A murine Ehrlich breast cancer model provided evidence for the efficacy and safety of Lf/BER-HA50-SF via tumoral, histological, immunohistochemical, molecular and systemic toxicity assessments. Thus, HA-SF nanoconjugates integrating the HA and SF properties and biofunctionalties present a novel biopolymer-biosurfactant platform of benefit to oncology nanomedicine and possibly other applications.