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

Hannah R Shanks,Daman J Adlam,Louise Carney,Amir H Milani,Christopher Blount,Dongdong Lu,Judith A Hoyland,Mark Dickinson,Brian R Saunders

doi:10.1021/acs.biomac.9b00463

Abstract

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.

Highlights

Injectable gels are highly desirable biomaterials that have been investigated for delivery,[1−11] tissue engineering,[12−16] and load support.[17−20] In all of these examples, the ability to noninvasively locate and monitor the gels remotely is advantageous for clinicians and researchers
Because we demonstrate that CSS particles are a versatile and highly sensitive reporter for remote NIR imaging and monitoring of gel swelling, they should have good potential for future biomaterial applications
We investigated the effect of pH on the PL response for the doubly cross-linked microgel (DX MG)/CSS/AF gels

Summary

■ INTRODUCTION

Injectable gels are highly desirable biomaterials that have been investigated for delivery,[1−11] tissue engineering,[12−16] and load support.[17−20] In all of these examples, the ability to noninvasively locate and monitor the gels remotely is advantageous for clinicians and researchers. This behavior is because gel swelling decreases the number of CSS particles per unit volume. Including CSS and AF within an implantable gel demonstrated generality of our approach for monitoring gel swelling remotely using both ratiometric and single intensity NIR PL measurements The fact that these gels are load-bearing suggests that they have potential future applications in vivo, such as augmentation of degenerated IVDs. NIR Imaging of an Injected DX MG/CSS/AF Gel. we investigated the ability to use DX MG/CSS/AF as an injectable gel for NIR imaging. The use of 470 nm wavelength enabled internal energy transfer to the NIR775 emission A potential limitation of NIR imaging using an excitation wavelength of 470 nm is that it only has an epidermis penetration depth of approximately 0.3 mm.[60]

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES