In recent years, a large variety of nanoparticle-based therapeutic agents has been widely developed for the treatment of various diseases because they can improve therapeutic effect and reduce bad side effect. However, poor cellular uptake of drug delivery carriers and uncontrolled drug release remain to be the major obstacles in cancer therapy due to their low delivery efficiency.
Recently, Shi Zhang Qiao’s group at the University of Adelaide developed a multifunctional intracellular GSH (glutathione, a tripeptide reducing agent in the cells)-responsive silica-based drug delivery system with enhanced cellular uptake capability. Firstly, uniform 50 nm colloidal mesoporous silica nanoparticles with mercaptopropyl-functionalized core and silanol-contained silica surface were designed and fabricated as an advanced carrier platform for both drug covalent attachment in the particle interior and polymer modification on the particle surface. Then, doxorubicin with primary amine group as a typical anticancer model drug was covalently conjugated to the mesopores in the interior of mesoporous silica nanoparticles via disulfide bonds in the presence of a heterobifunctional linker. Finally, the non-toxic, naturally creating and biodegradable peptide, poly(g-glutamic acid) (g-PGA), was coated onto the particle surface by sequential adsorption of non-toxic short polyethyleneimine and g-PGA via electrostatic interaction.
The constructed delivery system not only exhibited enhanced cellular uptake via a speculated g-glutamyl transpeptidase (GGT, an enzyme existed in cell membranes of many tissues)-mediated endocytosis pathway, but also demonstrated controlled intracellelular drug release capacity via GSH-responsive disulfide-bond cleavage, and thus significantly inhibited the growth of cancer cells. Thus, the multifunctional delivery system may pave a new way for developing high-efficient particle-based nanotherapeutic approach for cancer treatment.