This study aimed to enhance the water solubility and antitumor efficacy of (-)-
gossypol.
Polyethyleneimine conjugated with
stearic acid (PgS) was used for loading and protecting (-)-
gossypol through hydrogen bonding. Double-layered
hyaluronic acid (HA)-modified PgS nanoparticles encapsulating (-)-
gossypol [(-)-G-PgSHAs] were prepared through a two-step fabrication process. The nanoparticles possessed a uniform spherical shape with a dynamic size of 110.9 ± 2.4 nm, which was determined through transmission electron microscopy and dynamic light scattering analysis. The encapsulation efficiency and
drug-loading capacity of (-)-G-PgSHAs were 72.6% ± 3.1% and 9.1% ± 0.42%, respectively. The IR spectra of the samples confirmed the protection effect of hydrogen bonding on the optical activity of the encapsulated (-)-
gossypol. (-)-G-PgSHAs exhibited a controlled and
tumor-specific release because of the high expression of HAase in the
tumor region. The
tumor-targeting feature of PgSHAs due to HA-receptor mediation was confirmed by in vitro cell uptake and in vivo near infrared fluorescence imaging. The in vitro test showed that the (-)-G-PgSHAs had similar cytotoxicity to free (-)-
gossypol and was smaller than that of the encapsulated (±)-
gossypol [(±)-G-PgSHAs]. The in vivo study of the anti-
cancer effect of (-)-G-PgSHAs revealed that (-)-G-PgSHAs had a more enhanced
tumor-suppression effect and reduced systemic toxicity compared with free (-)-
gossypol and (±)-G-PgSHAs (P < 0.05). Therefore, PgSHA was a useful (-)-
gossypol nanocarrier that exhibits high biocompatibility, tunable release of
drug, and
tumor-targeting characteristics for
cancer treatment. In addition, this double-layered nanocarrier provided novel strategies for the encapsulation of other chiral drugs.