Synergic thermo- and pH-sensitive hybrid microgels with self-assembled fluorescent dyes and ultrasmall gold nanoparticles for intracellular raman sensing, photoacoustic imaging and photothermal therapy
- Authors
- Publication Date
- Jul 01, 2022
- Source
- HAL
- Keywords
- Language
- English
- License
- Unknown
- External links
Abstract
The design of smart hydrogel particles doped with plasmonic nanoparticles has attracted great in-terest in recent years due to their promising outlook in nanomedicine as therapeutic systems and bioimag-ing agents. Nanocomposite microgels were found particularly interesting as contrast agents for photoacoustic imaging (PAI), an emerging noninvasive and inexpensive bio-imaging modality, with promising prospects for cancer theranostics. Microgels can act as protective carriers to incorporate photoacoustic im-aging contrast agents thanks to their high loading capacity, biocompatibility and stimuli-responsive proper-ties. Plasmonic nanoparticles (NPs) are promising candidates for PAI contrast agents due to their outstanding optical properties based on localized surface plasmon (LSP). However, the synthesis of hybrid materials based on microgels doped with plasmonic NPs is a challenging task with the necessity to control sever-al features, such as particle sizes and doping levels in order to tailor their final properties in relation to the targeted application. To meet this challenge, we have developed in this PhD work an innovative modular strategy to achieve the rational design of well-defined and densely filled hybrid particles. It is based on the step-by-step self-assembly of the different building blocks, including microgels, dyes and gold nanoparticles and the tuning of nanoparticle loading within the polymer matrix through successive incubation steps, leading to densely filled microgels. A polymer matrix made of copolymers of oligo(ethylene glycol) methyl ether methacrylate and methacrylic acid was chosen to provide a polyanionic building block with swelling/deswelling response, pH- and thermo-sensitive behavior, desirable colloidal stability and biodegradability. Three different dyes were loaded within the microgels: rhodamine 6G (R6G), methylene blue (MB) and cyanine 7.5 (Cy), resulting in microparticles with optical emission extending from the visible to the NIR range. Gold NPs (Au NPs) coated with citrates were selected as the plasmonic building blocks due to their outstanding optical properties, based on the collective oscillations of free electrons at the particle surface, resulting in so-called localized surface plasmon resonances (LSPR). Upon light excitation of LSPR, a strong electromagnetic field enhancement is produced at the NP surface, leading to a wide range of applications in the fields of biology and chemistry, including surface enhanced Raman spectroscopy (SERS), bioimaging and sensing. In addition, Au NPs are able to convert the absorbed light into heat through non-radiative energy dissipation, making them valuable light-to-heat plasmonic converters for biomedical hyperthermia and PAI contrast agents. The characterization of the final hybrid networks using complementary techniques, such as UV-vis absorption, fluorescence, Raman, photoacoustic imaging, transmission electron microscopy and dynamic light scattering revealed that they uniquely combine the properties of hydrogel particles, including high loading capacity and stimuli-responsive behavior, the photoluminescent properties of dyes (rhodamine 6G, methylene blue and cyanine 7.5) and the features of gold nanoparticles assembly. Once the system was characterized, the potential of the final hybrid networks for biomedical science was assessed through photothermal experiments, photoacoustic and Raman imaging as well as cell viability assays. Interestingly, pH and temperature stimuli could be used to induce the shrinkage of the smart hybrid microgels resulting in Au NPs aggregation, plasmon coupling and improved absorption in the NIR region. Therefore, the final hybrid networks not only combine the remarkable features of each component but also display synergetic properties that open promising prospects for a broad range of bio-medical applications.
