Human Umbilical Cord Wharton’s Jelly-Derived Mesenchymal Stem Cells Labeled with Mn²⁺ and Gd³⁺ Co-Doped CuInS₂–ZnS Nanocrystals for Multimodality Imaging in a Tumor Mice Model

Abstract

Mesenchymal stem cell (MSCs) therapy has recently received profound interest as a targeting platform in cancer theranostics because of inherent tumor-homing abilities. However, the terminal tracking of MSCs engraftment by fluorescent in situ hybridization, immuno-histochemistry, and flow-cytometry techniques to translate into clinics is still challenging because of a dearth of inherent MSCs-specific markers and FDA approval for genetic modifications of MSCs. To address this challenge, a cost-effective noninvasive imaging technology based on multifunctional nanocrystals (NCs) with enhanced detection sensitivity, spatial–temporal resolution, and deep-tissue diagnosis is needed to be developed to track the transplanted stem cells. A hassle-free labeling of human umbilical cord Wharton’s Jelly (WJ)-derived MSCs with Mn2+ and Gd3+ co-doped CuInS2−ZnS (CIS-ZMGS) NCs has been demonstrated in 2 h without requiring an electroporation process or transfection agents. It has been found that WJ-MSCs labeling did not affect their multilineage differentiation (adipocyte, osteocyte, chondrocyte), immuno-phenotypes (CD44+, CD105+, CD90+), protein (β-actin, vimentin, CD73, α-SMCA), and gene expressions. Interestingly, CIS-ZMGS-NCs-labeled WJ-MSCs exhibit near-infrared (NIR) fluorescence with a quantum yield of 84%, radiant intensity of ∼3.999 × 1011 (p/s/cm2/sr)/(μW/cm2), magnetic relaxivity (longitudinal r 1 = 2.26 mM–1 s–1, transverse r 2 = 16.47 mM–1 s–1), and X-ray attenuation (78 HU) potential for early noninvasive multimodality imaging of a subcutaneous melanoma in B16F10-tumor-bearing C57BL/6 mice in 6 h. The ex vivo imaging and inductively coupled plasma mass-spectroscopy analyses of excised organs along with confocal microscopy and immunofluorescence of tumor results also significantly confirmed the positive tropism of CIS-ZMGS-NCs-labeled WJ-MSCs in the tumor environment. Hence, we propose the magnetofluorescent CIS-ZMGS-NCs-labeled WJ-MSCs as a next-generation nanobioprobe of three commonly used imaging modalities for stem cell-assisted anticancer therapy and tracking tissue/organ regenerations.

Optical Properties of Mn-Doped CuGa(In)S-ZnS Nanocrystals (NCs): Effects of Host NC and Mn Concentration

“…Among many multinary NCs, I(II)-III-VI NCs such as Cu-In-S/ZnS and Cu-Zn-In-S/ZnS NCs do not contain any Cd or Se elements and are particularly attractive to biomedical applications [ 22 , 23 , 24 , 25 , 26 ]. Different from binary excitonic NCs, they are donor–acceptor-pair-model-based materials.…”

“…Different from binary excitonic NCs, they are donor–acceptor-pair-model-based materials. In these NCs, the donor states could be attributed to sulfur vacancies, silver/copper interstitials and gallium/indium atoms occupying substituted silver/copper sites, and the acceptor states could be from indium/gallium interstitials and silver/copper atoms occupying gallium/indium sites [ 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. The fluorescence of I(II)-III-VI NCs should be mainly attributed to the electron transition from the donor states to acceptor states [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ].…”

Revealing Exciton and Metal–Ligand Conduction Band Charge Transfer Absorption Spectra in Cu-Zn-In-S Nanocrystals

“…Ternary semiconductors such as copper indium sulfide (CIS) quantum dots (QDs) have displayed very interesting optoelectronic properties for applications in photovoltaic devices, [1][2][3] LEDs, 4 and biomarkers. 5 CIS QD colloidal dispersions show long charge-carrier radiative recombination lifetimes (hundreds of nanoseconds), a large molar extinction coefficient from the visible to the near-infrared spectrum (10 5 L mol -1 cm -1 ), and large Stokes shifts (~250 to 500 meV) free of reabsorption effects. 6,7 However, CIS QDs have a low photoluminescence quantum yield (PLQY) (< 10%) due to their large density of defects.…”

Cell membrane camouflaged biomimetic nanoparticles: Focusing on tumor theranostics

“…In another study [ 55 ], CuInS 2 –ZnS (CIS-ZMGS) NPs were camouflaged WJ-derived MSC (WJ-MSCs) for FL, CT and MRI ( Fig. 8 ).…”