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A facile strategy is reported here for synthesis of Zn-Cu-In-S/ZnS (ZCIS/ZnS) core/shell QDs to address the synthetic issues that the unexpected blue-shift of CuInS(2)-based nanocrystals. In this strategy, Zn(2+) ions are intentionally employed for the synthesis of alloyed ZCIS core QDs before ZnS shell coating, which contributes to the reduced blue-shift in photoluminescence (PL) emission. The experimental results demonstrate this elaborate facile strategy is effective for the reduction of blue-shift during shell growth. Particularly, a hypothesis is proposed and proved for explanation of this effective strategy. Namely, both cation exchange inhibition and ions accumulation are involved during the synthesis of ZCIS/ZnS QDs. Furthermore, the obtained near infrared (NIR) ZCIS/ZnS QDs are transferred into aqueous phase by a polymer coating technique and coupled with cyclic Arg-Gly-Asp peptide (cRGD) peptides. After confirmation of biocompability by cytotoxicity test on normal 3T3 cells, these QDs are injected via tail vein into nude mice bearing U87 MG tumor. The result indicates that the signals detected in the tumor region are much more distinguishing injected with ZCIS/ZnS-cRGD QDs than that injected with ZCIS/ZnS QDs.

Gadolinium (Gd)-based nanoparticles are known for their high potential in magnetic resonance imaging (MRI). However, further MRI applications of these nanoparticles are hampered by their relatively large sizes resulting in poor organ/tumor targeting. In this study, ultrafine sub-10 nm and biocompatible Gd-based nanoparticles are synthesized in a bioinspired, environmentally benign, and straightforward fashion. This novel green synthetic strategy is developed for growing dextran-coated Gd-based nanoparticles (GdNPs@Dex). The as-prepared GdNPs@Dex is not only biocompatible but also stable with a sub-10 nm size. It exhibits higher longitudinal and transverse relaxivities in water (r1 and r2 values of 5.43 and 7.502 s-1 × 10-3 m-1 of Gd3+ , respectively) than those measured for Gd-DTPA solution (r1 and r2 values of 3.42 and 3.86 s-1 × 10-3 m-1 of Gd3+ , respectively). In vivo dynamic T1 -weighted MRI in tumor-bearing mice shows GdNPs@Dex can selectively target kidneys and tumor, in addition to liver and spleen. GdNPs@Dex is found particularly capable for determining the tumor boundary with clearly enhanced tumor angiogenesis. GdNPs@Dex is also found cleared from body gradually mainly via hepatobiliary and renal processing with no obvious systemic toxicity. With this green synthesis strategy, the sub-10 nm GdNPs@Dex presents promising potentials for translational biomedical imaging applications.

A new type of membrane fusogenic lipid was prepared to deliver DNA or siRNA into the cytoplasm directly in a fusion-dependent manner in order to bypass the cellular endocytosis to avoid the inefficient escape from the endosome and low transfection efficacy.

Ocular diseases include various anterior and posterior segment diseases. Due to the unique anatomy and physiology of the eye, efficient ocular drug delivery is a great challenge to researchers and pharmacologists. Although there are conventional noninvasive and invasive treatments, such as eye drops, injections and implants, the current treatments either suffer from low bioavailability or severe adverse ocular effects. Alternatively, the emerging nanoscience and nanotechnology are playing an important role in the development of novel strategies for ocular disease therapy. Various active molecules have been designed to associate with nanocarriers to overcome ocular barriers and intimately interact with specific ocular tissues. In this review, we highlight the recent attempts of nanotechnology-based systems for imaging and treating ocular diseases, such as corneal d iseases, glaucoma, retina diseases, and choroid diseases. Although additional work remains, the progress described herein may pave the way to new, highly effective and important ocular nanomedicines., Graphical abstract In this review, we highlights recent advances in development of nanotechnology-based systems, which could deliver both ocular drugs and gene to the eye via cornal absorption, periocular injection, and intravitreal injection, for ocular disease therapy and diagnosis. Both of nanosystems application and challenge in ophthalmology have been discussed and prospected.fx1

A simple, straightforward, and reproducible strategy for the construction of a near-infrared (NIR) fluorescence nanoprobe was developed by coating CuInS2/ZnS quantum dots (CIS/ZnS QDs) with a novel amphiphilic bioconjugate. The amphiphilic bioconjugate with a tailor-designed structure of bovine serum albumin (BSA) as the hydrophilic segment and poly(ε-caprolactone) (PCL) as the hydrophobic part was fabricated by chemical coupling the hydrophobic polymer chain to BSA via the maleimide-sulfhydryl reaction. By incorporating CIS/ZnS QDs into the hydrophobic cores of the self-assembly of BSA-PCL conjugate, the constructed NIR fluorescence nanoprobe exhibited excellent fluorescent properties over a wide pH range (pH 3-10) and a good colloidal stability in PBS buffer (pH = 7.4) with or without 10% fetal bovine serum. The presence of the outer BSA shell effectively reduced the nonspecific cellular binding and imparted high biocompatibility and low-toxicity to the probe. Moreover, the NIR fluorescence nanoprobe could be functionalized by conjugating cyclic Arg-Gly-Asp (cRGD) peptide, and the decorated nanoprobe was shown to be highly selective for targeted integrin αvβ3-overexpressed tumor cell imaging. The feasibility of the constructed NIR fluorescence probe in vivo application was further investigated and the results demonstrated its great potential for in vivo imaging. This developed protocol for phase transfer of the CIS/ZnS QDs was universal and applicable to other nanoparticles stabilized with hydrophobic ligands.

Functionalized quantum dots (QDs) have been widely explored for multimodality bioimaging and proven to be versatile agents. Attaching positron-emitting radioisotopes onto QDs not only endows their positron emission tomography (PET) functionality, but also results in self-illuminating QDs, with no need for an external light source, by Cerenkov resonance energy transfer (CRET). Traditional chelation methods have been used to incorporate the radionuclide, but these methods are compromised by the potential for loss of radionuclide due to cleavage of the linker between particle and chelator, decomplexation of the metal, and possible altered pharmacokinetics of nanomaterials. Herein, we described a straightforward synthesis of intrinsically radioactive [(64)Cu]CuInS/ZnS QDs by directly incorporating (64)Cu into CuInS/ZnS nanostructure with (64)CuCl2 as synthesis precursor. The [(64)Cu]CuInS/ZnS QDs demonstrated excellent radiochemical stability with less than 3% free (64)Cu detected even after exposure to serum containing EDTA (5 mM) for 24 h. PEGylation can be achieved in situ during synthesis, and the PEGylated radioactive QDs showed high tumor uptake (10.8% ID/g) in a U87MG mouse xenograft model. CRET efficiency was studied as a function of concentration and (64)Cu radioactivity concentration. These [(64)Cu]CuInS/ZnS QDs were successfully applied as an efficient PET/self-illuminating luminescence in vivo imaging agents.

Inorganic nanoparticles have been introduced into biological systems as useful probes for in vitro diagnosis and in vivo imaging, due to their relatively small size and exceptional physical and chemical properties. A new kind of colortunable Gd-Zn-Cu-In-S/ZnS (GZCIS/ZnS) quantum dots (QDs) with stable crystal structure has been successfully synthesized and utilized for magnetic resonance (MR) and fluorescence dual modality imaging. This strategy allows successful fabrication of GZCIS/ZnS QDs by incorporating Gd into ZCIS/ZnS QDs to achieve great MR enhancement without compromising the fluorescence properties of the initial ZCIS/ZnS QDs. The as-prepared GZCIS/ZnS QDs show high T 1 MR contrast as well as “color-tunable” photoluminescence (PL) in the range of 550–725 nm by adjusting the Zn/Cu feeding ratio with high PL quantum yield (QY). The GZCIS/ZnS QDs were transferred into water via a bovine serum albumin (BSA) coating strategy. The resulting Cd-free GZCIS/ZnS QDs reveal negligible cytotoxicity on both HeLa and A549 cells. Both fluorescence and MR imaging studies were successfully performed in vitro and in vivo. The results demonstrated that GZCIS/ZnS QDs could be a dual-modal contrast agent to simultaneously produce strong MR contrast enhancement as well as fluorescence emission for in vivo imaging.

P-glycoprotein (P-gp) can pump a wide variety of structurally unrelated compounds out of cells. However the mechanism of this pumping action remains uncertain. Based on the view that the basic interaction between biological molecules is electric and the change of free energy decides the direction and limit of a reaction, using Debye-Huckel theory and incorporating the simplified structured model of P-glycoprotein, the change of electrostatic free energy in the process of substrates entering the lumen of P-glycoprotein is induced. It is proposed that the main reason of substrates entering the lumen of P-glycoprotein with a high effectiveness is the action of electrostatic free energy. The energy minimum of transporting a substrate is obtained, which has the same order as the energy from one ATP hydrolyzed. It is illustrated that one ATP needs to be hydrolyzed per substrate transported. Two indirect ways to inhibit the action of P-glycoprotein multidrug resistance are proposed.

Synthesis of CuInS-based quantum dots (QDs) in the organic phase is currently one of the fastest growing points of nanotechnology. Most of the reported CuInS-based QDs are hydrophobic and cannot be directly used for biomedical applications without phase transfer. We put forward a one-pot synthetic strategy aimed at fabricating hydrophilic Zn–Cu–In–S/ZnS (ZCIS/ZnS) quantum dots (QDs) to be used directly for in vivo imaging without surface treatment. This strategy is based on the use of a hydrophilic ligand (6-sulfanyl-1-hexanol, MPH) and non-coordinating solvents such as a low molecular weight polyethylene glycol (PEG, MW = 400 Da). The capping ligand MPH endows the obtained ZCIS/ZnS QDs with good hydrophilicity and therefore offers great opportunity for direct bioimaging applications without phase transfer. Experimental results have indicated that these so-called hydrophilic ZCIS/ZnS QDs show low cytotoxicity and are successfully utilized for in vivo imaging. Furthermore, the here reported strategy doesn't only present a synthetic idea, but also might stimulate other innovative ideas on fabricating hydrophilic or water-soluble ZCIS/ZnS QDs to be used directly for biological applications.