A lysine-rich cell penetrating peptide engineered multifunctional gold nanoparticle-based drug delivery system with enhanced cellular penetration and stability

Engineered peptide-based drug delivery systems have gained substantial momentum in the field of diagnostics and therapeutics owing to their superior biocompatibility, facilitation in cellular interactions and selective targeting of diseased cells. However, the use of any cell penetrating peptide (a lysine-rich BP100 (KKLFKKILKYL-Amide) in the present case has to be carefully optimized in terms of drug loading, release, targeting and internalization into cells as compared to conventional peptide such as RGD. Keeping this in mind, we have synthesized and compared the efficacy of two drug delivery systems-one which was functionalized with cell penetrating peptide BP100 (BP100@AuNPs) and the other one with a targeting peptide RGD (RGD@AuNPs). Both were functionalized onto gold nanoparticles (AuNPs) and loaded with doxorubicin (DOX) to investigate their internalization and therapeutic capabilities. The synthesized BP100@AuNPs-DOX and RGD@AuNPs-DOX nanoconjugates were thoroughly characterized using UV–visible spectroscopy, TEM, FTIR and TGA. Both the nanoconjugates displayed efficient internalization and anticancer activity. Interestingly, BP100@AuNPs-DOX exhibited a higher payload capacity and pH responsive controlled release of DOX as compared to the RGD@AuNPs-DOX. These studies significantly underpin the role of cell penetrating peptide, BP100 as a multifunctional cofactor in the nanoparticle based delivery system which can pave the way for the design and development of targeted nanobioprobes against cancer and other diseases. Graphical abstract