Near-Infrared Fluorescent Ag2 Se-Cetuximab Nanoprobes for Targeted Imaging and Therapy of Cancer.

Theranostic nanoprobes integrated with diagnostic imaging and therapy capabilities have shown great potential for highly effective tumor therapy by realizing imaging-guided drug delivery and tumor treatment. Developing novel high-performance nanoprobes is an important basis for tumor theranostic application. Here, near-infrared (NIR) fluorescent and low-biotoxicity Ag2 Se quantum dots (QDs) have been coupled with cetuximab, a clinical antiepidermal growth factor receptor antibody drug for tumor therapy, via a facile bioconjugation strategy to prepare multifunctional Ag2 Se-cetuximab nanoprobes. Compared with the Ag2 Se QDs alone, the Ag2 Se-cetuximab nanoprobes display faster and more enrichment at the site of orthotopic tongue cancer, and thus present better NIR fluorescence contrast between the tumor and the surrounding regions. At 24 h postinjection, the NIR fluorescence of Ag2 Se-cetuximab nanoprobes at the tumor site is still easily detectable, whereas no fluorescence is observed for the Ag2 Se QDs. Moreover, the Ag2 Se-cetuximab nanoprobes have also significantly inhibited the tumor growth and improved the survival rate of orthotopic tongue cancer-bearing nude mice from 0% to 57.1%. Taken together, the constructed multifunctional Ag2 Se-cetuximab nanoprobes have achieved combined targeted imaging and therapy of orthotopic tongue cancer, which may greatly contribute to the development of nanotheranostics.

Reversible covalent nanoassemblies for augmented nuclear drug translocation in drug resistance tumor.

The drug efflux by P-glycoprotein (P-gp) is the primary contributor of multidrug resistance (MDR), which eventually generates insufficient nuclear drug accumulation and chemotherapy failure. In this paper, reversible covalent nanoassemblies on the basis of catechol-functionalized methoxy poly (ethylene glycol) (mPEG-dop) and phenylboronic acid-modified cholesterol (Chol-PBA) are successfully synthesized for delivery of both doxorubicin (DOX, anti-cancer drug) and tariquidar (TQR, P-glycoprotein inhibitor), which shows efficient nuclear DOX accumulation for overcoming tumor MDR. Through naturally forming phenylboronate linkage in physiological circumstances, Chol-PBA is able to bond with mPEG-dop. The resulting conjugates (PC) could self-assemble into reversible covalent nanoassemblies by dialysis method, and transmission electron microscopy analysis reveals the PC distributes in nano-scaled spherical particles before and after drug encapsulation. Under the assistance of Chol, PC can enter into lysosome of tumor cells via low-density lipoprotein (LDL) receptor-mediated endocytosis. Then the loaded TQR and DOX are released in acidic lysosomal compartments, which inhibit P-gp mediated efflux and elevate nuclear accumulation of DOX, respectively. At last, this drug loaded PC nanoassemblies show significant tumor suppression efficacy in multidrug-resistant tumor models, which suggests great potential for addressing MDR in cancer therapy.

Cu-In-S/ZnS:Gd3+ quantum dots with isolated fluorescent and paramagnetic modules for dual-modality imaging in vivo.

Gd3+-doped quantum dots (QDs) have been widely used as small-sized bifunctional contrast agents for fluorescence/magnetic resonance (FL/MR) dual-modality imaging. However, Gd3+ doping will always compromise the FL of host QDs. Therefore, balancing the Gd3+ doping and the optical properties of QDs is crucial for constructing high-performance bifunctional nanoprobes. Additionally, most paramagnetic QDs are synthesized in the organic phase and need to be transferred to the aqueous phase for bioimaging. Herein, ingeniously designed shell-doped Cu-In-S/ZnS:Gd3+ QDs have been prepared in the aqueous phase. It has been demonstrated that isolating paramagnetic Gd3+ from fluorescent Cu-In-S core via doping Gd3+ into ZnS shell not only avoided the decrease of FL quantum yield (QY), but also ensured the water accessibility of paramagnetic Gd3+ ions, by which the FL QY and r1 relaxivity of Cu-In-S/ZnS:Gd3+ QDs achieved as much as 15.6% and 15.33 mM-1·s-1, respectively. These high-performance QDs with excellent stability, low biotoxicity, and good tumor permeability were successfully applied for in vivo tumor FL/MR dual-modality imaging, and have shown significant potential in the precision detection and diagnosis of diseases.

Small-sized copolymeric nanoparticles for tumor penetration and intracellular drug release.

Poor solid-tumor penetration of nanocarriers limits the drug efficacy. Herein, small-sized copolymeric nanoparticles are prepared for delivering the chemotherapeutic drug DOX into solid tumors deeply and releasing the drug effectively. These small-sized copolymeric nanoparticles represent substantial potential for clinical translation.

A highly reactive chalcogenide precursor for the synthesis of metal chalcogenide quantum dots.

Metal chalcogenide semiconductor nanocrystals (NCs) are ideal inorganic materials for solar cells and biomedical labeling. In consideration of the hazard and instability of alkylphosphines, the phosphine-free synthetic route has become one of the most important trends in synthesizing selenide QDs. Here we report a novel phase transfer strategy to prepare phosphine-free chalcogenide precursors. The anions in aqueous solution were transferred to toluene via electrostatic interactions between the anions and didodecyldimethylammonium bromide (DDAB). The obtained chalcogenide precursors show high reactivity with metal ions in the organic phase and could be applied to the low-temperature synthesis of various metal chalcogenide NCs based on a simple reaction between metal ions (e.g. Ag(+), Pb(2+), Cd(2+)) and chalcogenide anions (e.g. S(2-)) in toluene. In addition to chalcogenide anions, other anions such as BH4(-) ions and AuCl4(-) ions can also be transferred to the organic phase for synthesizing noble metal NCs (such as Ag and Au NCs).

Ag2Se quantum dots with tunable emission in the second near-infrared window.

Quantum dots (QDs) with fluorescence in the second near-infrared window (NIR-II, 1000-1400 nm) are ideal fluorophores for in vivo imaging of deep tissue with high signal-to-noise ratios. Ag2Se (bulk band gap 0.15 eV) is a promising candidate for preparing NIR-II QDs. By using 1-octanethiol as ligand to effectively balance the nucleation and growth, tuning the fluorescence of Ag2Se QDs was successfully realized in the NIR-II window ranged from 1080 to 1330 nm. The prepared Ag2Se QDs can be conveniently transferred to the aqueous phase by ligand exchange, showing great potential for multicolor NIR-II fluorescence imaging in vivo.

Water-soluble Ag(2)S quantum dots for near-infrared fluorescence imaging in vivo.

A one-step method for synthesizing water-soluble Ag(2)S quantum dots terminated with carboxylic acid group has been reported. The crystal structure and surface of the prepared Ag(2)S quantum dots were characterized. The prepared Ag(2)S quantum dots exhibited bright photoluminescence and excellent photostabilities. The photoluminescence emissions could be tuned from visible region to near-infrared (NIR) region (from 510 nm to 1221 nm). Ultra-small sized Ag(2)S nanoclusters were synthesized with high initial monomer concentration in the current system. The in vivo imaging experiments of nude mice showed that the NIR photoluminescence of the prepared Ag(2)S quantum dots could penetrate the body of mice. Compared to the conventional NIR quantum dots, the Ag(2)S quantum dots don't contain toxic elements to body (such as Cd and Pb), thus, the prepared Ag(2)S quantum dots could serve as excellent NIR optical imaging probes and would open the opportunity to study nanodiagnostics and imaging in vivo.