Microwave‐Assisted Synthesis of Quasi‐Pyramidal CuInS₂–ZnS Nanocrystals for Enhanced Near‐Infrared Targeted Fluorescent Imaging of Subcutaneous Melanoma

Abstract

Near‐infrared (NIR) fluorescent CuInS2–ZnS nanocrystals (CIZS NCs) are synthesized via an ultra‐fast, non‐injection microwave (MW)‐assisted nanoalloying process at 230 ºC within 5 min using 1‐dodecanethiol (DDT) as both the sulfur source and solvent under solvothermal (ST) condition. The structural and surface analyses reveal that DDT‐functionalized CIZS NCs exhibit quasi‐pyramids of tetragonal‐phase with well‐defined facets. The DDT‐functionalized CIZS NCs present a photoluminescence quantum yield (PLQY) of 76% and a long‐lived fluorescence lifetime of ≈0.6 µs in organic‐phase. Subsequently, DDT‐functionalized CIZS NCs are phase‐transferred via ligand‐exchange using 11‐mercaptoundecanoic acid (MUA) into water‐soluble MUA–CIZS NCs that exhibit a substantial PLQY of 55%. In addition, the NIR‐fluorescent MUA‐functionalized CIZS NCs in conjugation with folic acid (FA), as a tumor‐targeting ligand, demonstrates enhanced tumor‐targeted imaging ability. The FA–MUA–CIZS NC conjugates exhibit a cell viability of ≈75% even at the highest concentration of 1 mg mL–1 and a labeling efficiency of 95.4%. The in vivo imaging results corroborate that FA–MUA–CIZS NCs conjugates are actively targeted to folate receptor‐positive B16F10 tumor‐bearing C57BL/6 mice in 2 h. The histopathological and hematological studies confirm no significant changes in tissue architecture and blood biochemical parameters. The confocal microscopy studies reveal deep penetration and uniform distribution of FA–MUA–CIZS NCs conjugates in subcutaneous melanoma.

The Photoluminescence and Biocompatibility of CuInS2-Based Ternary Quantum Dots and Their Biological Applications

“…Due to the high polarity of the (112) plane in the CIS tetragonal phase, the surface energy increased and grew very fast along the [112] direction. Similar results were observed by Chetty et al [51].…”

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

“…28 The ex vivo imaging of the major organs and the tumor confirmed the NIR-fluorescence signal in the upper lobe of the lungs because of transient pulmonary trapping, slightly in the liver because of the enhanced permeability and retention (EPR) effect, and enhanced NIR- h because of elimination from mice. 24,25 The biodistribution of CIS-ZMGS NCs was confirmed by ex vivo imaging and ICP−MS analysis. Our results corroborated the recent studies on Gd-chelate-entrapped MSCs for detection of an early tumor (∼3 mm 3 ) using 4.7 T MR and optical imaging in 2 h by Kim et al 12 Also, the tumor homing ability of peptide-conjugated nanophosphor-labeled adiposederived stem cells (ASCs) in 24 h post-injection in a 4T1 tumor-bearing mice model was reported by Wu et al 49 However, the result concluded minimal tropism of ASCs in the 4T1 tumor owing to early sequestration by phagocytes in lung capillaries in contrast to accumulation in the liver.…”

“…However, further increase in reaction temperature resulted in destabilization and aggregation of surface-functionalized 1-DDT ligands, resulting in a drastic quenching in emission of MW-R synthesized NCs. 24 Despite effective capping of 1-DDT ligands on the NCs surface, there exist surface-related defects because of a high surface/volume ratio that facilitates nonradiative recombinations. Hence, the cation exchange or nanoalloying of ZnS was utilized to eliminate the surface defects and increase the confinement of electrons and holes in NCs.…”

“…Cultured B16F10 melanoma cells (∼10 5 ) were subcutaneously transplanted on the shoulder and left hind limb toward the skeletal muscle of adult C57BL/6 mice (20−25 g). 24 After the tumor attained the desired growth, B16F10 tumor-bearing C57BL/6 mice models were used for in vivo imaging experiments. Briefly, 50 μL of CIS-ZMGS NCslabeled WJ-MSCs (10 6 ) were intravenously injected via the tail vein in tumor-bearing C57BL/6 mice (n = 3) and imaged after 6 h to monitor the tropism in the tumor microenvironment by an IVIS Lumina III in vivo imaging system (excitation: 470 nm, emission: 650 nm), a Philips Achieva 1.5 T MRI, and a Siemens SOMATOM Spirit four-slice CT scanner (120 kV, 200 mAs and 476 mA, exposure time 420 ms/rotation with slice thickness 0.8 mm, field of view, FOV 50 mm).…”

“…23 Further, we developed a rapid, noninjection microwave-refluxing (MW-R) nanoalloying method for the synthesis of CIZS NCs and subsequent conjugation with folic acid for enhanced NIRfluorescent imaging of subcutaneous melanoma in C57BL/6 mice. 24 We also demonstrated a hot-injection, two-step, lowcost MW-R process to synthesize CIZS NCs for labeling MSCs to prepare an MSCs-CIZS nanobioconjugate for NIRfluorescence imaging of engraftment and liver regeneration abilities in acetaminophen-induced liver-injured mice. 25 Recently, Cao et al reported the synthesis of high-quality Mn 2+ -doped CIZS NCs QDs using a multistep hot injection approach with PL QY of 66% and extremely long PL lifetime of ∼3.78 ms. 26 Manna et al explained doping of Mn 2+ in the CIZS host, which quenches intrinsic defect-state emissions and exhibits spin-flip Mn emissions.…”