First-Of-Its-Kind Self-Assembled Nanoparticle for Targeted and Triggered Thermo-Chemotherapy
Research from investigators at the MIT-Harvard Center of Cancer Nanotechnology Excellence has succeeded in designing and demonstrating the effectiveness of first-of-its-kind, self assembled, multi-functional, near-infrared (NIR) responsive gold nanorods that can deliver a chemotherapy drug specifically targeted to cancer cells and selectively release the drug in response to an external beam of light while creating heat for synergistic thermo-chemo mediated anti-tumor efficacy. NIR is minimally absorbed by skin and tissue, has the ability to penetrate deep tissue in a noninvasive way, and can be converted to heat by gold nanomaterials for effective thermal ablation of diseased tissue. The results of this study were published by Omid Farokhzad and his colleagues in the journal Angewandte Chemie International Edition.
“The design of this gold nanorod and its self-assembly was inspired by nature and the ability of complimentary strands of DNA to hybridize on their own without imposing complicated chemical processes on them,” explained Dr. Farokhzad, director of the Laboratory of Nanomedicine and Biomaterials at Brigham and Women’s Hospital. “Each functionalized DNA strand individually, and the self assembled components as a system, play a distinct yet integrative role resulting in synergistic targeted and triggered thermo-chemotherapy capable of eradicating tumors in our pre-clinical models.”
One DNA strand is attached to the gold nanorod and the complementary strand is attached to a stealth layer and a homing molecule that keeps the system under the radar of the immune system while targeting it directly to cancer cells. When the DNA strands come together, the targeted gold nanorod is formed and the double stranded DNA serves as the scaffold for binding the chemotherapy drug, doxorubicin, which can be released in response to NIR light that concurrently results in generation of heat by the gold nanorods. Each of the three distinct functional components plays a role in contributing to the triple punch of triggered thermotherapy, controlled doxorubicin release, and cancer cell targeting.
To demonstrate the robust capability of this nanorod system, Dr. Farokhzad and his collaborators used a pre-clinical model to evaluate the in vivo anti-tumor efficacy in two different tumor models and four different groups with different drug regiments, each group varying in weight and tumor size. Researchers administrated an injection of the novel, self-assembled nanoparticle and then 10 minutes post-injection, the tumors were irradiated using NIR light that activated the nanoparticle using the gold nanorod and created heat. The results showed that this platform successfully delivered heat and anti-cancer drugs to synergistically eradicate tumors.
“Thermal ablation is already commonly used in cancer treatment,” said Dr. Farokhzad. “What is extremely exciting about this platform is that we are able to selectively target cancer cells and then hit the tumor twice: first with a controlled release of a chemotherapy drug and then secondly with triggered induction of heat from the activation of the gold nanorod. And all this can be done noninvasively.”
This work, which is detailed in a paper titled, “DNA self-assembly of targeted near-infrared-responsive gold nanoparticles for cancer thermo-chemotherapy,” was supported in part by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract of this paper is available at the journal's website.