Abstract
Curcumin is a potent natural polyphenol with established anti-neoplastic, anti-inflammatory, and antioxidant properties; however, its clinical translation is severely hindered by poor aqueous solubility, rapid metabolic degradation, and low systemic bioavailability. In this study, we report the rational design and comprehensive molecular characterization of curcumin-loaded PEGylated liposomal nanocarriers integrated with plasmonic gold nanoparticles for targeted delivery and real-time vibrational tracking. Surface-Enhanced Raman Spectroscopy (SERS) coupled with dispersion-corrected Density Functional Theory (DFT) calculations at the B3LYP-D3/6-311+G(d,p) level of theory was utilized to elucidate the structural conformation, tautomeric equilibrium, and membrane-intercalation behavior of curcumin within the dipalmitoylphosphatidylcholine (DPPC) lipid bilayer. SERS spectra revealed significant enhancement of vibrational modes associated with the central keto-enol moiety and phenolic rings, confirming that the enol tautomer predominantly stabilizes via hydrogen bonding within the hydrophobic acyl core of the liposome. In vitro drug release kinetics demonstrated sustained, pH-responsive release profiles under acidic tumor microenvironment conditions (pH 5.5) relative to physiological pH (7.4). Furthermore, cellular uptake and cytotoxicity assays in human breast adenocarcinoma (MCF-7) cells confirmed superior intracellular delivery and enhanced apoptotic efficacy compared to free curcumin. This integrated physical-chemical approach establishes a robust paradigm for analyzing nanocarrier-drug interactions at the molecular level, advancing the formulation of next-generation theranostic nanoplatforms for targeted cancer therapy.
