Adsorption of Cathepsin B-sensitive peptide conjugated DOX on nanodiamonds

Drug delivery mediated by nanodiamonds (NDs) has shown great promise in controlled drug release field. In present study, dipeptide (Phe-Lys) conjugated antitumor drug doxorubicin hydrochloride (DOX) with self-immolative p-aminobenzylcarbonyl (PABC) spacer was non-covalently bound to carboxylated NDs via the electrostatic interactions. HIV-1 trans-activating transcriptor peptide (TAT) was additionally integrated to this ND-based delivery system in order to enhance the transmembrane efficiency. Fourier transforms infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and zeta potentials were applied to characterize the DOX and TAT loaded ND delivery platform. The adsorption equilibrium, kinetics and thermodynamics for the adsorption of peptide conjugated DOX onto NDs were investigated. It was found that the adsorption fitted well with the Freundlich model and conformed to pseudo-second order kinetics. It also showed that the adsorption was a spontaneous and exothermic process. Therefore, our work offered a facile way to formulate a ND-based drug delivery platform with multifunctionality in a layer by layer adsorption fashion.

Graphical abstractCathepsin B-sensitive peptide Phe-Lys conjugated DOX (Phe-Lys-PABC-DOX) and HIV-1 trans-activating transcriptor (YGRKKRRQRRR, denoted as TAT) were adsorbed onto carboxylated nanodiamonds (NDs) sequentially via the electrostatic interactions. The adsorption equilibrium, adsorption kinetics and thermodynamics of Phe-Lys-PABC-DOX onto the NDs were investigated.Download full-size imageHighlights► Phe-Lys-PABC-DOX (PD) and HIV-1 trans-activating transcriptor (TAT) peptide were sequentially adsorbed onto NDs. ► The adsorption characteristics of PD by NDs were determined and the electrostatic interaction between PD and NDs was verified. ► The present work provided a non-covalent adsorption method to construct ND based drug delivery system with multifunctionality in a layer by layer fashion.