Development of a targeted nanoscale drug delivery system using pH-responsive DNA-nanoparticle conjugate

• Main Author: Song, Lei
• Other Authors: Zhou, Dejian
• Published: University of Leeds 2013
• Subjects: 616.99
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.707026

Cancer is one of the most devastating diseases facing society, accounting for some 8 millions deaths worldwide in 2008 alone, and, more alarmingly, the number is predicted to increase to 13.1 million in 2030. Although conventional cancer treatments, such as radiotherapy and chemotherapy, have provided profound beneficial effects for millions of cancer patients, serious side effects cannot be avoided, mostly due to the lack of specific targeting of these treatments. A long-term goal for the pharmaceutical and healthcare industries is to develop intelligent drug delivery systems that can selectively target and deliver drugs specifically to tumour region, to maximize their therapeutic index and reduce side-effects. Nanotechnology, the “next Industrial Revolution”, offers the possibility of developing new materials, structures, devices and systems at the atomic and molecular levels that have significantly improved physicochemical properties. One of the most exciting developments in nanotechnology is that of nanoscale drug delivery systems, which are expected to change the landscape of pharmaceutics in the near future. These innovative nanoscale drug delivery systems are capable of improving transcytosis of drugs across tight epithelial and endothelial barriers, targeting drugs to cell- or tissue-specific sites and delivering macromolecule drugs to intracellular sites of action. Inspired by such promise, this project aims to combine a pH-responsive DNA nanomachine with a biocompatible gold nanoparticle (GNP) to develop a new nanoscale tumour-targeting drug delivery system. Doxrubicin (DOX), a model anticancer drug, can bind to the system quickly and efficiently, and be released in a pH-responsive manner. This system is further modified by polyethylene glycol (PEG) for improved stability and stealth effect. Thus it has the potential to act as an excellent drug carrier. Preliminary cellular studies reveal that this system is able to deliver DOX to model (HeLa) cancer cells through the endocytic pathway, and that its cell-killing efficiency is comparable to that of the drug on its own. Furthermore, targeting ligands can be attached to this type of system for active targeting, and other functioning inorganic nanoparticles (i.e. gold nanorods and gold-coated magnetic nanoparticles) can also be used to replace the GNP as scaffold. This should allow the development of a multifunctional drug delivery system with the potential to offer more effective multi-modal therapeutic and imaging modalities.