Control of blood clotting using gold nanorods

Abstract

We have developed a method to externally control blood clotting using gold nanoparticles. Gold nanorods (NRs) have unique size and shape-dependent optical properties that can be used for externally controlled release of biomolecules by laser excitation. Femtosecond pulsed laser irradiation at the NR longitudinal surface plasmon resonance peak (LSPR) can excite the NRs and induce melting, and thus cause release of drug or biomolecular payload on the NR. Because the peak wavelength of the LSPR changes with NR aspect ratio, NRs with different aspect ratios can be independently excited at different wavelengths to release different payloads in a mutually exclusive fashion. This approach can be used to create a biological switch for blood clotting by releasing a single stranded (ssDNA) thrombin binding aptamer (TBA) upon laser irradiation. It is possible to control blood clotting by releasing TBA that binds and inhibits thrombin, and an antidote consisting of a complementary ssDNA sequence that binds to TBA and restores thrombin activity. Both the TBA and the antidote are loaded onto NRs with different aspect ratios. This enables us to use laser excitation at one wavelength to deliver the TBA and inhibit thrombin and consequently blood clotting. We then use a different wavelength to deliver the antidote and reverse the effect of the TBA. We use covalent attachment techniques (thiol-gold binding) for loading the ssDNA on the NRs and study the interface between the NRs and the biomolecules. We also take advantage of serum protein coronas for loading, which enable enhanced loading capacities. This localized, selective and externally controlled release of biomolecules represents an advance that could impact a number of biological applications, where the current practice is systemically administering drugs though the whole bloodstream and relying on physiological clearance to restore the system.