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Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic technique that can induce the regression of targeted lesions via generating excess cytotoxic reactive oxygen species. However, due to the limited penetration depth of visible excitation light and the intrinsic hypoxia microenvironment of solid tumors, the efficacy of PDT in the treatment of cancer, especially deep-seated or large tumors, is unsatisfactory. Herein, we developed an efficient in vivo PDT system based on a nanomaterial, dihydrolipoic acid coated gold nanocluster (AuNC@DHLA), that combined the advantages of large penetration depth in tissue, extremely high two-photon (TP) absorption cross section (σ2 ∼ 106 GM), efficient ROS generation, a type I photochemical mechanism, and negligible in vivo toxicity. With AuNC@DHLA as the photosensitizer, highly efficient in vivo TP-PDT has been achieved.

We here report a facile synthesis of chitosan shelled quantum dot (QD/fGC) that holds essential properties requisite for biological applications, such as excellent water solubility, super colloidal stability, and low nonspecific adsorption as well as ease of functionalization. In this method, the amphiphilic glycol chitosan fragment (MW 1.0-1.7 kDa) was assembled on the top of CdSeS/ZnS nanocrystal through hydrophobic interaction in aqueous solution, without displacing the native coordinating ligands, which result in a higher quantum yield of about 0.26, 46% of the uncoated CdSeS/ZnS QDs in chloroform (0.57). In addition, the prepared QD/fGC composes an individual semiconductor core and presents an extremely small size of about 6.03 ± 1.50 nm (n = 399) in diameter. By conjugation with bioactive amines via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-based hydroxyl activation approach, the functionalized QD/fGC presented excellent recognition of specific cells in fluorescent imaging. Our work provides a new general method of chitosan modification of hydrophobic nanoparticles for biomedical applications.

High-resolution dynamic force mapping of cardiomyocytes is revealed by nanopillars with piezo-phototronic effect., Dynamic mapping of the cell-generated force of cardiomyocytes will help provide an intrinsic understanding of the heart. However, a real-time, dynamic, and high-resolution mapping of the force distribution across a single living cell remains a challenge. Here, we established a force mapping method based on a “light nano-antenna” array with the use of piezo-phototronic effect. A spatial resolution of 800 nm and a temporal resolution of 333 ms have been demonstrated for force mapping. The dynamic mapping of cell force of live cardiomyocytes was directly derived by locating the antennas’ positions and quantifying the light intensities of the piezo-phototronic light nano-antenna array. This study presents a rapid and ultrahigh-resolution methodology for the fundamental study of cardiomyocyte behavior at the cell or subcellular level. It can provide valuable information about disease detection, drug screening, and tissue engineering for heart-related studies.

The solid-phase peptide synthesis (SPPS) strategy, as the main procedure of peptide manufacturing, has a profound impact on the research of peptides. The rapid development of nanotechnology is expected to promote the evolution of the solid phase to miniaturization, convenience and multi-function. In this work, silica-coated magnetic ferriferous oxide (Fe3O4) nanoparticles (MNP/SiO2) were used as new generation of solid phase for SPPS in Fmoc chemistry. The superparamagnetic solid phase facilitated a multi-step synthesis reaction due to its magnetic maneuverability, which could efficiently separate reaction intermediates, and were then redispersed in the next-step synthetic solution for peptide elongation. In addition, this strategy further allowed the simultaneous acquisition of magnetic nanoparticle–peptide conjugates as available bioprobes to examine the biological function of synthesized peptides. The feasibility of this novel magnetic nanoparticle-based solid phase peptide synthesis (MNP-SPPS) strategy was confirmed by the synthesis of arginine-glycine-aspartic acid-glycine-glycine (RGDGG) as a model pentapeptide. The simultaneously acquired magnetic nanoparticle–peptide conjugates (RGDGG-MNP/SiO2), possessing excellent biological functions, could be recognized and further internalized by tumor cells through receptor-mediated endocytosis, thereby achieving the extraction and removal of malignant cells in vitro under an external magnetic field. The RGDGG-MNP/SiO2 could further be used as a contrasting agent for tumor-targeting T2 magnetic resonance imaging in vivo. This study developed a novel MNP-SPPS strategy that could realize the simple synthesis of peptides, and the synchronously obtained nanoprobes could quickly detect the biological activity of the target synthetic sequence. This strategy may have broad application prospects in combinatorial chemistry and the construction of peptide libraries in the future.

Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic technique that can induce the regression of targeted lesions

Bioimaging or bioanalysis based on nanoprobes encapsulating Eu 3 + complexes with excellent two-photon-sensitized (TPS) luminescence properties combines the advantages of deep penetration, high sensitivity, high signal-to-noise ratio, stable signals during long term observation, low photodamage to biological samples, and desirable target recognizability. The TPS luminescence of lanthanide complexes is produced through the two-photon excitation (TPE) of a lightharvesting antenna ligand and subsequent excitation energy transfer (EET) to the metal ions, which provides a promising manner for extending the excitation windows of lanthanide complexes to the near-infrared (NIR) light wavelength region. In the last two decades, remarkable progress has been achieved in the design and synthesis of two-photonsensitized luminescent lanthanide complexes. [1] Several lanthanide complexes have been applied to the multiphoton-excited bioimaging of cells. [2–4] Due to the characteristic luminescence properties of Eu 3 + complexes, such as the characteristic narrow-line emission in the red-light wavelength region with acceptable transparence for many biosamples, high luminescence quantum yields, large Stokes shifts, and long luminescence lifetime (millisecond order), the TPS Eu 3 + luminescence is of significance for developing bioanal

Oligosaccharides play crucial roles in many biorecognition processes by the so-called "cluster glycosidic effect". We here report a facile synthesis of lactose-CdSeS/ZnS quantum dot conjugate (Lac-QDs) by use of 1-thiol-beta-D-lactose via ligand exchange, which exhibits significantly high affinity and specificity to leukocytes in contrast to the monovalent lactose. Structural analyses indicate that there are about 132 lactosyl molecules assembled on single QDs and the hydrodynamic diameter is small, close to 8.2 nm. Further, Lac-QDs display good fluorescence and physicochemical stability in physiological conditions, as well as extremely low cytotoxicity. These properties facilitate the use of Lac-QDs in fluorescent labeling of live leukocytes.

In recent years, silica coating has been extensively investigated to fabricate the biocompatible interface of quantum dots (QDs) for biomedical applications. We here describe a facile and efficient method of synthesizing high-quality silica-coated CdSeS QDs (CdSeS QD/SiO(2)), where an immediate photoluminescence-favorable microenvironment is first created by assembling amphiphilic molecules around the CdSeS core, and a thin silica shell is further introduced to protect this hydrophobic interlayer. The prepared CdSeS QD/SiO(2) exhibits excellent properties such as good water solubility, low cytotoxicity, and high quantum yield (QY, up to 0.49) as well as the resistance of photobleaching in aqueous solution. Also, the CdSeS QD/SiO(2) nanoparticles homogeneously comprise single CdSeS cores and hold a comparatively small size up to about 11 nm in diameter. Particularly, this method leads to a significant increase in QY as compared to the uncoated CdSeS QDs ( approximately 109% of the initial QY), though only thin silica shells formed in the CdSeS QD/SiO(2) structure. By coupling with folic acids, the CdSeS QD/SiO(2) conjugates were successfully used for tumor cell labeling. Our results demonstrated a robust hydrophobic QDs-based approach for preparing highly photoluminescent, biocompatible QD/SiO(2) through creation of a stable hydrophobic interlayer surrounding the QD cores, which could be also suitable for silica coating of other kinds of hydrophobic nanoparticles.

Luminescence thermometry usually suffer from cellular complexity of the biochemical environment (such as pH and ionic strength) and thus the accuracy and reliability of the determined intracellular temperature are directly affected. Herein, a photoluminescent nanothermometer composed of polymer encapsulated quantum dots (P-QD) has been developed. And the prepared nanothermometer exhibits some advantages: such as non-sensitivity to pH and ionic strength, as well as high detection sensitivity and ultrahigh reversibility. The intracellular temperature was accurately determined under physiological conditions with different pH and ionic strength and direct measurement of thermogenesis in individual cells has been achieved.

Materials possessing high two photon absorption (TPA) are highly desirable for a range of fields, such as three-dimensional data storage, TP microscopy (TPM) and photodynamic therapy (PDT). Specifically, for TPM, high TP excitation (TPE) brightness (σ × ϕ, where σ is TPA cross-sections and ϕ is fluorescence quantum yield), excellent photostability and minimal cytotoxicity are highly desirable. However, when TPA materials are transferred to aqueous media through molecule engineering or nanoparticle formulation, they usually suffer from the severely decrease of quantum yield (QY). Here, we report a convenient and efficient method for preparing polymer-encapsulated quantum dots (P-QD). Interestingly, the QY was considerably enhanced from original 0.33 (QDs in THF) to 0.84 (P-QD in water). This dramatic enhancement in QY is mainly from the efficiently blocking nonradiative decay pathway from the surface trap states, according to the fluorescence decay lifetimes analysis. The P-QD exhibits extremely high brightness (σ × ϕ up to 6.2 × 106 GM), high photostability, excellent colloidal stability and minimal cytotoxicity. High quality cellular TP imaging with high signal-to-background ratio (> 100) and tissue imaging with a penetration depth of 2200 μm have been achieved with P-QD as probe.

Monitoring mitochondria morphological changes temporally and spatially exhibits significant importance for diagnosing, preventing and treating various diseases related to mitochondrial dysfunction. However, the application of commercially available mitochondria trackers is limited due to their poor photostability. To overcome these disadvantages, we designed and synthesized a mitochondria-localized fluorescent probe by conjugating 1,8-naphthalimide with triphenylphosphonium (i.e. NPA-TPP). The structure and characteristic of NPA-TPP was characterized by UV-vis, fluorescence spectroscopy, (HNMR)-H-1, (CNMR)-C-13, FTIR, MS, etc. The photostability and cell imaging were performed on the laser scanning confocal microscopy. Moreover, the cytotoxicity of NPA-TPP on cells was evaluated using (3-[4,5-dimethylthiazol-2-y1]-2,5 diphenyl tetrazolium bromide) assay. The results showed that NPA-TPP not only has high sensitivity and specificity to mitochondria, but also exhibits super-high photostability, negligible cytotoxicity and good water solubility. In short, NPA-TPP indicates great potential for targeting mitochondria and enables a real-time and long-term tracking mitochondrial dynamics changes. (C) 2015 Elsevier B.V. All rights reserved.

Fluorescence microscopy has become an essential tool for biological research because it can be minimally invasive, acquire data rapidly, and target molecules of interest with specific labeling strategies. However, the diffraction-limited spatial resolution, which is classically limited to about 200 nm in the lateral direction and about 500 nm in the axial direction, hampers its application to identify delicate details of subcellular structure. Extensive efforts have been made to break diffraction limit for obtaining high-resolution imaging of a biological specimen. Various methods capable of obtaining super-resolution images with a resolution of tens of nanometers are currently available. These super-resolution techniques can be generally divided into three primary classes: (1) patterned illumination-based super-resolution imaging, which employs spatially and temporally modulated illumination light to reconstruct sub-diffraction structures; (2) single-molecule localization-based super-resolution imaging, which localizes the profile center of each individual fluorophore at subdiffraction precision; (3) bleaching/blinking-based super-resolution imaging. These super-resolution techniques have been utilized in different biological fields and provide novel insights into several new aspects of life science. Given unique technical merits and commercial availability of super-resolution fluorescence microscope, increasing applications of this powerful technique in life science can be expected.