pH-Triggered Charge-Reversal Silk Sericin-Based Nanoparticles for Enhanced Cellular Uptake and Doxorubicin Delivery

Silk-based nanoparticles have been exhibiting an increasing potential for use as drug delivery systems due to their great versatility. To extend applications of silk sericin in nanomedicine and improve the performance of silk-based nanoparticles in drug delivery, a facile two-step cross-linking is attempted, for the first time, to fabricate surface charge-reversal silk sericin-based nanoparticles (SSC@NPs) by introducing chitosan into silk sericin. The results suggest stable SSC@NPs are formed with a negative surface charge in a neutral environment. Under mildly acidic conditions, however, surface charge of SSC@NPs undergoes a negative-to-positive conversion. It proves that pH can regulate surface charge of SSC@NPs. It is the increased amino/carboxyl ratio in SSC@NPs that explains the underlying mechanism of the charge conversion property of SSC@NPs. Furthermore, the positively charged SSC@NPs triggered by tumor acidic microenvironment (pH 6.0) result in a 6.0-fold higher cellular uptake than the negatively charged counterparts at pH 7.4. In addition, an anticancer drug doxorubicin (DOX) is readily loaded into SSC@NPs and released in a pH-dependent manner. This work provides a simple method to fabricate smart pH-responsive nanoparticles for anticancer drug delivery.