Penetrating Peptide-Bioconjugated Persistent Nanophosphors for Long-Term Tracking of Adipose-Derived Stem Cells with Superior Signal-to-Noise Ratio

Abstract

Reliable long-term in vivo tracking of stem cells is of great importance in stem cell-based therapy and research. Fluorescence imaging with in situ excitation has significant autofluorescence background, which results in poor signal-to-noise ratio (SNR). Here we report TAT penetrating peptide-bioconjugated long persistent luminescence nanoparticles (LPLNP-TAT) for long-term tracking of adipose-derived stem cells (ASC) without constant external excitation. LPLNP-TAT exhibits near-infrared emitting, red light renewable capability, and superior in vivo imaging depth and SNR compared with conventional organic dye and quantum dots. Our findings show that LPLNP-TAT can successfully label ASC without impairing their proliferation and differentiation and can effectively track ASC in skin-regeneration and tumor-homing models. We believe that LPLNP-TAT represents a new generation of cell tracking probes and will have broad application in diagnosis and therapy.

Functionalized phosphorescent nanoparticles in (bio)chemical sensing and imaging – A review

“…In these sense, zinc gallate (ZGO) and gallogermanate (ZGGO) hosts have demonstrated to overcome the limitations previously mentioned due to the possibility to re-excite PLNPs in vivo using orange/red light-emitting diodes (LEDs), allowing NPs detection for several days in small animals [89,90]. This new generation of PLNPs has been further functionalized with different biomolecules to be successfully used in active targeting [87,88,89]. Moreover, multimodal contrast agents have been developed combining PLNPs with a metal complex or other kind of NPs to obtain multimodal probes that present persistent luminescence and simultaneously, magnetic resonance [90,91] or X-ray computed tomography features [92].…”

Chemically engineered persistent luminescence nanoprobes for bioimaging

“…In 2016, Yan and co-workers reported the first fabrication of TAT penetrating peptide-functionalized NIR-emitting PLNPs with composition Zn 1.1 Ga 1.8 Ge 0.1 O 4 :Cr 3+ , Eu 3+ (LPLNP-TAT) for long-term tracking of stem cells 128. The prepared LPLNP-TAT have been successfully used to label stem cells and showed excellent biocompatibility, high signal-to-noise ratio (SNR).…”

“…(B) In vivo biodistribution of LPLNP-TAT and LPLNP-TAT-labeled ASC after intravenous injection. Reproduced with permission from reference 128.…”

Nanohybrids with Magnetic and Persistent Luminescence Properties for Cell Labeling, Tracking, In Vivo Real‐Time Imaging, and Magnetic Vectorization

“…Acting as optical capacitors, PLNPs can emit light in the tissue transparency window for minutes to hours after the end of an UV or visible illumination, leading to signals without autofluorescence and high target to background ratio . Recently, ultrasensitive detection of labeled cells in small animals either after intravenous or subcutaneous injection was demonstrated in preliminary studies using PLNPs …”