Tumor‐Targeted Multimodal Optical Imaging with Versatile Cadmium‐Free Quantum Dots

Abstract

The rapid development of fluorescence imaging technologies requires concurrent improvements in the performance of fluorescent probes. Quantum dots have been extensively used as an imaging probe in various research areas because of their inherent advantages based on unique optical and electronic properties. However, their clinical translation has been limited by the potential toxicity especially from cadmium. Here, a versatile bioimaging probe is developed by using highly luminescent cadmium-free CuInSe2/ZnS core/shell quantum dots conjugated with CGKRK (Cys–Gly–Lys–Arg–Lys) tumor-targeting peptides. This probe exhibits excellent photostability, reasonably long circulation time, minimal toxicity, and strong tumor-specific homing property. The most important feature of this probe is that it shows distinctive versatility in tumor-targeted multimodal imaging including near-infrared, time-gated, and two-photon imaging in different tumor models. In a glioblastoma mouse model, the targeted probe clearly denotes tumor boundaries and positively labels a population of diffusely infiltrating tumor cells, suggesting its utility in precise tumor detection during surgery. This work lays a foundation for potential clinical translation of the probe.

Biocompatible Semiconductor Quantum Dots as Cancer Imaging Agents

“…However, low pH can cause the dissociation or oxidation of monodentate thiols . To avoid this dissociation issue, ligands containing a hydrophobic spacer between the thiol and the hydrophilic group have been utilized to create QD dispersions that are stable for over a month . Another strategy to generate homogeneous dispersions under aqueous conditions after organic phase synthesis is to encapsulate the QDs in an amphiphilic polymer.…”

“…QD targeting based on the overexpression of cell surface proteins has been reported for breast and pancreatic cancer. Liu et al published a CuInSe 2 /ZnS based core–shell system surface conjugated with Cys–Gly–Lys–Arg–Lys (CGKRK), a peptide that binds to a tumor cell membrane biomarker . They used this system to target mice bearing an orthotopic MCF10CA1a breast cancer xenograft.…”

“…In recent years, many heavy element‐free QDs have been developed with emission in the NIR‐I and NIR‐II windows. Various methods have been employed to reach emissions of higher wavelength such as fine tuning the core precursor ratios, varying the core synthesis temperature to increase core size, and using the seeds of the initial growth for a secondary growth process . These NIR emitting QDs have been used in vivo for various proof‐of‐concept experiments to demonstrate both active and passive tumor targeting for real‐time imaging of tumors as described in Table 3 including imaging of breast cancer xenografts in mice, real time SLN mapping of metastatic breast cancer in mice, and in vivo imaging of glioblastoma…”

Nanomaterial-based biosensors for detection of pathogenic virus

“…QDs light emission is a useful property for a lot of medical labeling, imaging or sensing applications such as to distinguish between normal and tumor cells [21] gene therapy studies [22], proteomics [23], etc. From the perspective of virology, QDs are useful tools for providing rapid and sensitive virus detection to facilitate early treatment and monitoring of viral disease.…”

A54 peptide-mediated functionalized gold nanocages for targeted delivery of DOX as a combinational photothermal-chemotherapy for liver cancer

“…Homing peptides have been considered as the most promising targeting agents for human tumors owing to their several merits, including their relatively small molecular weights, ease of synthesis, low immunogenicity, good biocompatibility, and biodegradable characteristics in vivo. 29 It has been reported that A54 peptide (sequence AGKGTPSLETTP) is the most specific and effective targeting agent to the BEL-7402 human hepatoma carcinoma cell line via cell surface markermediated endocytosis. 30 In this work, we developed a novel tumor cell-specific targeted AuNCs-based drug delivery system (doxorubicin [DOX]-loaded, HA-grafted, and A54 peptide-targeted PEGylated AuNCs, abbreviated as DHTPAuNCs) and then investigated their therapeutic effects for the first time (Scheme 1).…”