Core–Shell–Shell Nanoparticles for NIR Fluorescence Imaging and NRET Swelling Reporting of Injectable or Implantable Gels

Injectable gels that support load are desirable for restoring the mechanical properties of degenerated load-bearing tissue. As these gels become increasingly sophisticated, the need to remotely image them and monitor their swelling increases. However, imaging such gels and monitoring their swelling using noninvasive means is challenging. Here, we use a very low concentration of near-infrared (NIR) core–shell–shell (CSS) reporter nanoparticles to both image and monitor swelling changes of two load-supporting gels. The load-supporting injectable gel consisted of covalently interlinked pH-responsive microgel (MG) particles. The latter gel was not cytotoxic and is termed a doubly cross-linked microgel (DX MG). Inclusion of a complementary fluorescent dye enabled ratiometric monitoring of gel swelling changes in response to pH via nonradiative resonance energy transfer (NRET). In addition, changes in the CSS nanoparticle emission intensity provided a NIR-only method that could also be used to monitor gel swelling. The gel was able to be imaged using NIR light, after being subcutaneously injected into a tissue model. To demonstrate versatility of our approach, CSS and the dye were included within a model implantable gel (poly­(acrylamide/acrylic acid)) and fluorescent detection of swelling investigated. Because the concentrations of the reporting species were too low to affect the mechanical properties, our approach to remote gel imaging and swelling monitoring has good potential for application in injectable gels and implants.