الفهرس 
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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