Tuan Vo-Dinh

Fitzpatrick Institute for Photonics

Departments of Biomedical Engineering and Chemistry

Duke University

 

Plasmonic Nanoprobes:

Harnessing the Power of Photonics for Medical Diagnostics and Therapy

 

This lecture provides an overview of recent developments in our laboratory for several plasmonic nanoplatforms for medical diagnostics and therapy (theranostics). Plasmonics refers to the research area of enhanced electromagnetic properties of metallic nanostructures that produce ultrasensitive and selective detection technologies. The technology involves interactions of laser radiation with metallic nanoparticles, inducing very strong enhancement of the electromagnetic field on the surface of the nanoparticles. These processes, often called ‘plasmonic enhancements’, produce the surface-enhanced Raman scattering (SERS) effect that could enhance the Raman signal of molecules on these nanoparticles more than a million fold.

A SERS-based nanoprobe technology, referred to as ‘inverse Molecular Sentinel’ (iMS) nanoprobes, has been developed to detect DNA/mRNA targets of infectious agents (e.g., malaria, dengue, HIV) and biomarkers of cancer (e.g., BRCA1, ERB2 breast cancer genes). SERS-based plasmonic nanoprobes and nanochip systems have been developed for use as diagnostic systems for point-of-care personalized nanomedicine and global health applications.

In the field of therapy, gold nanostars (GNS) are of particular interest because their structure has multiple sharp branches that produce the ‘lightning rod’ effect that strongly enhances the local electromagnetic field when subject to light stimulation for photothermal therapy. Furthermore, GNS sizes can be controlled so that they passively accumulate in tumors due to the enhanced permeability and retention (EPR) effect of tumor vasculature for selective treatment of tumors. We have demonstrated that the use of plasmonic nanoparticles in combination with immunotherapy—a treatment we referred to as Synergistic Immuno Photothermal Nanotherapy (SYMPHONY)—can dramatically enhance the efficacy of immunotherapy. Remarkably, we have found that SYMPHONY not only eradicates primary “treated” tumors but also has resulted in the immune-mediated destruction of distant “untreated” metastatic tumors. This abscopal effect occurred uniquely when nanoparticle tumor heating was used in combination with immunotherapy. This strategy could lead to an entirely new treatment paradigm that challenges traditional surgical resection approaches for many cancers and metastases. Of great importance is the possibility that such our approach can induce long-term immunological memory that can provide protection against tumor recurrence long after treatment of the initial tumors similar to an “anti-cancer vaccine”.