Hierarchical Assembly of Liposomes with Shape-Controlled Metal Nanoparticles for Multifunctional Theranostics

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Multifunctional nanoparticles that simultaneously enable targeted diagnosis of a disease and delivery of a therapeutic drug are of significant interest to achieving highly specific disease detection and treatment in a single procedure. In this work a single multifunctional nanoparticle, Lipo-Nanoantennas, will be nanomanufactured for combined therapeutics and diagnostics (theranostics) in cancer cells. Lipo-Nanoantennas will ultimately facilitate a clinically applicable technology which can be translated from "bench to bedside" allowing minimally invasive imaging of cancer biomarkers with high precision. Lipo-Nanoantennas will also simultaneously deliver dose-controlled treatment minimizing off-target toxicities associated with chemotherapy. Further, Lipo-Nanoantennas may allow early detection and targeted treatment of multiple diseases including cardiovascular and infectious diseases. Successful implementation of the project goals will ultimately enable us to generate a library of functional nanomaterial assemblies that will impact multiple technologies including sensing, catalysis, and self-healing coatings. Notably, this project also builds an interface between the PI's research and core undergraduate chemical engineering curriculum where the PI teaches a drug delivery laboratory. Further, this work will increase participation of underrepresented minorities at the graduate and undergraduate level in the PI's lab, and propel research-based outreach activities among K-12 students.The objective of this award is to study the hierarchical assembly of thermosensitive liposomes with gold nanoantennas (Lipo-Nanoantennas) to enable multifunctional theranostics. This will leverage directed self-assembly, a bottom-up nanomanufacturing approach, that offers nanoscale control of material properties critical to enabling enhanced theranostics. Liposomes are clinically-approved drug carriers and nanoantennas are ideally suited for both imaging and converting near-infrared light to heat. Heat generated by the nanoantennas is absorbed by the liposomes disrupting the lipid bilayer and triggering drug release. Directed assembly of Lipo-Nanoantennas provides a mechanistic design of a nanomanufactured construct that can leverage intense photothermal response directly at the point of drug release. This gives rise to highly efficient photothermal drug delivery with minimal off-target toxicity and precise cellular imaging all with a single nanoscale entity. By controlling the loading density and shape of gold nanostructures within the liposomes, and their overall size and material properties, the photothermal response of Lipo-Nanoantennas will be manipulated to promote enhanced uptake, imaging, and drug release in cells. The Lipo-Nanoantennas will then be utilized for surface-enhanced Raman imaging and delivery of chemotherapeutic drugs in cancer cells. Our central hypothesis is that understanding directed-assembly of Lipo-Nanoantennas will offer a transformative approach relative to other methods that will simultaneously enable superior biophysical properties, and theranostics.