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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - NanoIntra (Multitasking Nanoparticles for Intracellular Bioimaging and Biosensing)

Teaser

Summary

The development of specifically designed nanomaterials for advanced medical applications such as theranostics has become a major technical challenge with great potential societal and economic outcomes. Nanomedicine and related techniques hold great promises for improved diagnostic and treatment of widely spread diseases such as cancer.
This project aims at developing novel multitasking nanoparticles as advanced tools for highly localized and ultrasensitive intracellular imaging and biosensing. These nanoprobes should provide new insights in the spatial and temporal processes at play in live cells. Such functional objects are achieved through the design of complex architectures involving semiconductor quantum dots as bright and stable luminescent material. These nanocrystals are combined with plasmonic nanoparticles, which offer new strategies for their photothermally induced intracellular delivery. The targeting and imaging of specific subcellular structures is then achieved thanks to proper surface functionalization of the nanoparticles. In addition, the plasmonic nanocrystals also allow these nanoparticles to be used as Surface Enhanced Raman Scattering (SERS) biosensors.
Besides their application in cell labeling and biosensing, these functional nanoparticles have tremendous potential applications in the fields of theranostics, nanomedicine, nanobiophotonics, and NanoIntra constitutes a first step toward the development of a full lab-on-a-particle. Through the synthesis and characterization of novel materials and their application to biotechnology, NanoIntra is a multidisciplinary research and training project at the interface between physics, chemistry and biology.

Work performed

The first two years of the project were conducted in the group of Prof. Wiesner at Cornell University in the United States. This period was dedicated to the synthesis and development of these new materials with complex architectures. In this regards, new methods have been established for the synthesis of luminescent quantum dots with improved optical properties and their encapsulation in silica nanoparticles as a biocompatible material (Fig. 1). In addition, this silica matrix provided a versatile platform for the subsequent surface functionalization with zwitterionic groups. During this period, it was demonstrated that such functionalization allowed endosomal uptake of the nanoparticles by live cells (Fig. 1), while ensuring good colloidal stability. New methods have also been investigated for the synthesis of ultrasmall and water soluble plasmonic gold and/or silver nanoparticles. These metal nanoparticles can thereafter bind to silica coated quantum dots thanks to prior surface modification with amine or thiol groups.
In parallel, new nanoparticles structures have also been discovered through the self-assembly of mesoporous silica. This approach resulted in particular in the formation of ultrasmall particles with dodecahedral cage and ring morphologies (Fig. 2). Given the versatility of silica surface chemistry, and the ability to distinguish the inside and outside of the cages and rings, these materials might prove themselves particularly useful as cargo containers for smart drug delivery strategies.

Final results

As an important finding during this period, the surface functionalization of the nanoparticles with zwitterionic group was optimized in order to balance colloidal stability and efficient endosomal uptake. This provides a good alternative to traditional functionalization with polyethylene glycol which typical hinder the uptake of nanoparticles by live cells. In addition, the shorter length of the zwitterionic groups and their smaller footprint on the surface of the nanoparticles will allow the nanoparticles to accommodate more easily the additional functionalization with metal nanoparticles, which will constitute a great asset moving forward into the project.
Nevertheless, a variety of new diagnostic and therapeutic probes with drugs hidden inside nanoparticles with cage-like structures can also be envisaged, hence offering interesting complementarities to the multitasking nanoparticles investigated in this project, with important potential impact for the field of nanomedicine.