Versatile Self-Assembly of Water-Soluble Thiol-Capped CdTe Quantum Dots: External Destabilization and Internal Stability of Colloidal QDs

In this paper, we report on the versatile self-assembly of water-soluble thiol-capped CdTe quantum dots (QDs), nanoparticles (NPs), or nanocrystals induced by l-cysteine (l-Cys). Major efforts are focused on the control of the self-organization of QDs into nanosheets (NSs), for example, by altering the solution pH and the QD size. The as-prepared nanosheets exhibit bright photoluminescence (PL) and retain the size-quantized properties of initial CdTe QDs, since they are actually formed by a 2D network of assembled QDs. By optical techniques, TEM, EDX, powder XRD, etc., it is found that the unique l-Cys-induced external destabilization is responsible for the template-free self-organization process, with the further assistance of the specific NP–NP interactions. And the internal chemical stability of initial CdTe QDs also is proven for the first time to play an important role. These results help to enhance the current understanding about the mechanism for the destabilization of colloidal NPs and their self-assembly behavior

FRET-Based Upconversion Nanoprobe Sensitized by Nd³⁺ for the Ratiometric Detection of Hydrogen Peroxide in Vivo

The exorbitant level of hydrogen peroxide is closely related to many human diseases. The development of novel probes for H2O2 detection will be beneficial to disease diagnosis. In this study, a novel Nd3+-sensitized upconversion nanoprobe based on Förster resonance energy transfer was first developed for sensing H2O2. This nanosystem was made of core–shell upconversion nanoparticles (emission at 540 and 660 nm), dicyanomethylene-4H-pyran (DCM)–H2O2, and poly acrylic acid (PAA)–octylamine. Obviously, upconversion nanoparticles (UCNPs) doped with Nd3+ acted as an energy donor, and DCM–H2O2, transferring to DCM–OH with the reaction of H2O2, acted as an energy acceptor. The ratiometric upconversion luminescence (540 nm/660 nm) signal could be utilized to visualize the H2O2 level, and the LOD of the nanoprobe for H2O2 was quantified to be 0.168 μM. Meanwhile, owing to the dope of Nd3+, the nanoprobe would not induce the overheating effect in biological samples and could possess deeper tissue penetration depth, compared with the UCNPs excited by 980 nm light during bioimaging. The nanoprobe could also play an important role in detecting the exogenous and endogenous H2O2 in living cells with ratiometric UCL (upconversion luminescence) imaging. Furthermore, our nanoprobe could function in detecting the H2O2 in a tumor-bearing mouse model. Therefore, this novel nanoprobe along with the ratiometric method for responding and bioimaging H2O2 could serve as a new model that promotes the emergence of novel probes for H2O2 detection

Discovery of Near-Infrared Heptamethine Cyanine Probes for Imaging-Guided Surgery in Solid Tumors

Near-infrared (NIR) fluorescence imaging has attracted much attention in image-guided interventions with unique advantages. However, the clinical translation rate of fluorescence probes is extremely low, primarily due to weak lesion signal contrast and poor specificity. To address this dilemma, a series of small-molecule near-infrared fluorescence probes have been designed for tumor imaging. Among them, YQ-04-03 showed notable optical stability and remarkable sensitivity toward tumor targeting. Moreover, within a specific concentration and time range against oxidizing reducing agents and laser, it demonstrated better stability than ICG. The retention time of YQ-04-03 in tumors was significantly longer compared to other nonspecific uptake sites in the subjects, and its tumor-to-normal tissue ratio (TNR) outperformed ICG. Successful resection of in situ hepatocarcinoma and peritoneal carcinoma was achieved using probe imaging guidance, with the smallest visual lesion resected measuring approximately 1 mm3. Ultimately, this probe holds great potential for advancing tumor tracer

Quaternary Zn–Ag–In–Se Quantum Dots for Biomedical Optical Imaging of RGD-Modified Micelles

Exploring the synthesis of new biocompatible quantum dots (QDs) helps in overcoming the intrinsic toxicity of the existing QDs composed of highly toxic heavy metals (e.g., Cd, Hg, Pb, etc.) and is particularly interesting for the future practical application of QDs in biomedical imaging. Hence, in this report, a new one-pot approach to oil-soluble (highly toxic heavy metal-free) highly luminescent quaternary Zn–Ag–In–Se (ZAISe) QDs was designed. Their photoluminescence (PL) emission could be systematically tuned from 660 to 800 nm by controlling the Ag/Zn feed ratio, and their highest PL quantum yield is close to 50% after detailed optimization. Next, by using biodegradable RGD peptide (arginine–glycine–aspartic acid)-modified N-succinyl-N′-octyl-chitosan (RGD-SOC) micelles as a water transfer agent, the versatility of these quaternary ZAISe QDs for multiscale bioimaging of micelles (namely, in vitro and in vivo evaluating the tumor targeting of drug carriers) was further explored, as a promising alternative for Cd- and Pb-based QDs

Discovery of Near-Infrared Heptamethine Cyanine Probes for Imaging-Guided Surgery in Solid Tumors

Near-infrared (NIR) fluorescence imaging has attracted much attention in image-guided interventions with unique advantages. However, the clinical translation rate of fluorescence probes is extremely low, primarily due to weak lesion signal contrast and poor specificity. To address this dilemma, a series of small-molecule near-infrared fluorescence probes have been designed for tumor imaging. Among them, YQ-04-03 showed notable optical stability and remarkable sensitivity toward tumor targeting. Moreover, within a specific concentration and time range against oxidizing reducing agents and laser, it demonstrated better stability than ICG. The retention time of YQ-04-03 in tumors was significantly longer compared to other nonspecific uptake sites in the subjects, and its tumor-to-normal tissue ratio (TNR) outperformed ICG. Successful resection of in situ hepatocarcinoma and peritoneal carcinoma was achieved using probe imaging guidance, with the smallest visual lesion resected measuring approximately 1 mm3. Ultimately, this probe holds great potential for advancing tumor tracer

FGF19-Based Mini Probe Targeting FGFR4 for Diagnosis and Surgical Navigation of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a frequent malignancy that has a high death rate and a high rate of recurrence following surgery, owing to insufficient surgical resection. Furthermore, HCC is prone to peritoneal metastasis (HCC-PM), resulting in a significant number of tiny cancer lesions, making surgical removal more challenging. As a potential imaging target, FGFR4 is highly expressed in tumors, especially in HCC, but is less expressed in the normal liver. In this study, we used computational simulation approaches to develop peptide I0 derived from FGF19, a particular ligand of FGFR4, and labeled it with the NIRF dye, MPA, for HCC detection. In surgical navigation, the TBR was 9.31 ± 1.36 and 8.57 ± 1.15 in HepG2 in situ tumor and HCC-PM models, respectively, indicating considerable tumor uptake. As a result, peptide I0 is an excellent clinical diagnostic reagent for HCC, as well as a tool for surgically resecting HCC peritoneal metastases

FGF19-Based Mini Probe Targeting FGFR4 for Diagnosis and Surgical Navigation of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a frequent malignancy that has a high death rate and a high rate of recurrence following surgery, owing to insufficient surgical resection. Furthermore, HCC is prone to peritoneal metastasis (HCC-PM), resulting in a significant number of tiny cancer lesions, making surgical removal more challenging. As a potential imaging target, FGFR4 is highly expressed in tumors, especially in HCC, but is less expressed in the normal liver. In this study, we used computational simulation approaches to develop peptide I0 derived from FGF19, a particular ligand of FGFR4, and labeled it with the NIRF dye, MPA, for HCC detection. In surgical navigation, the TBR was 9.31 ± 1.36 and 8.57 ± 1.15 in HepG2 in situ tumor and HCC-PM models, respectively, indicating considerable tumor uptake. As a result, peptide I0 is an excellent clinical diagnostic reagent for HCC, as well as a tool for surgically resecting HCC peritoneal metastases

FGF19-Based Mini Probe Targeting FGFR4 for Diagnosis and Surgical Navigation of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a frequent malignancy that has a high death rate and a high rate of recurrence following surgery, owing to insufficient surgical resection. Furthermore, HCC is prone to peritoneal metastasis (HCC-PM), resulting in a significant number of tiny cancer lesions, making surgical removal more challenging. As a potential imaging target, FGFR4 is highly expressed in tumors, especially in HCC, but is less expressed in the normal liver. In this study, we used computational simulation approaches to develop peptide I0 derived from FGF19, a particular ligand of FGFR4, and labeled it with the NIRF dye, MPA, for HCC detection. In surgical navigation, the TBR was 9.31 ± 1.36 and 8.57 ± 1.15 in HepG2 in situ tumor and HCC-PM models, respectively, indicating considerable tumor uptake. As a result, peptide I0 is an excellent clinical diagnostic reagent for HCC, as well as a tool for surgically resecting HCC peritoneal metastases

DNA Framework-Programmed Ligand Positioning to Modulate the Targeting Performance

Effective targeting of nanomedicine is still an intricacy since unsatisfactory clinical trial feedback demonstrated their inadequate concentration at the desired area. However, the regulatory effect of ligand-modification patterns on the targeting effect has not been surveyed yet. Based on the superior spatial addressability of DNA frame structures, herein DNA tetrahedrons were used as templates for site-specific modification of targeting ligands. In this work, nanovectors with homogeneous ligand-modification patterns, including various valence of ligands and the precisely controlled distance between ligands at the nanoscale, were established for the first time. In vitro and in vivo targeting performance studies found that merely relying on the augment of the ligand quantity exhibited a confined promotion effect on the targeting efficiency. Notably, the space distance between ligands displayed a more important role in reforming the targeting effect, and the largest ligand distance (approximately 156.55 Å) pattern exhibited an optimal targeting effect and prominently cytostatic activity toward tumor cells. Generally, the survey of ligand-modification patterns on nanovectors provided a valid guidance to direct the optimization of nanomedicine