Plasmonic Vesicles of Amphiphilic Nanocrystals: Optically Active Multifunctional Platform for Cancer Diagnosis and Therapy.

Vesicular structures with compartmentalized, water-filled cavities, such as liposomes of natural and synthetic amphiphiles, have tremendous potential applications in nanomedicine. When block copolymers self-assemble, the result is polymersomes with tailored structural properties and built-in releasing mechanisms, controlled by stimuli-responsive polymer building blocks. More recently, chemists are becoming interested in multifunctional hybrid vesicles containing inorganic nanocrystals with unique optical, electronic, and magnetic properties. In this Account, we review our recent progress in assembling amphiphilic plasmonic nanostructures to create a new class of multifunctional hybrid vesicles and applying them towards cancer diagnosis and therapy. Localized surface plasmon resonance (LSPR) gives plasmonic nanomaterials a unique set of optical properties that are potentially useful for both biosensing and nanomedicine. For instance, the strong light scattering at their LSPR wavelength opens up the applications of plasmonic nanostructures in single particle plasmonic imaging. Their superior photothermal conversion properties, on the other hand, make them excellent transducers for photothermal ablation and contrast agents for photoacoustic imaging. Of particular note for ultrasensitive detection is that the confined electromagnetic field resulting from excitation of LSPR can give rise to highly efficient surface enhanced Raman scattering (SERS) for molecules in close proximity. We have explored several ways to combine well-defined plasmonic nanocrystals with amphiphilic polymer brushes of diverse chemical functionalities. In multiple systems, we have shown that the polymer grafts impart amphiphilicity-driven self-assembly to the hybrid nanoparticles. This has allowed us to synthesize well-defined vesicles in which we have embedded plasmonic nanocrystals in the shell of collapsed hydrophobic polymers. The hydrophilic brushes extend into external and interior aqueous environment to stabilize the vesicular structure. More importantly, we have demonstrated that strong interparticle coupling greatly enhances the optical properties (scattering, photothermal conversion, and SERS) in plasmonic vesicles. In combination with the loading capacity of the vesicles, this technology can provide unique opportunities for integrated diagnosis and therapy, multimodality combination therapy, and imaging-guided therapy. One key property differentiating the plasmonic vesicles from other vesicular structures containing nanocrystals is that we can tailor the interparticle coupling and disintegration of the plasmonic vesicles by altering structural parameters and conformational changes of the covalently bound polymer brushes. This gives us tremendous flexibility to engineer plasmonic vesicles for ultrasensitive detection and targeted therapy. Through bringing together advances in nanochemistry, polymer chemistry, self-assembly, and nanophotonics, we expect to further expand our capability of tailoring optical and structural characteristics of plasmonic vesicles to address challenges in medical settings.