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Quantum dots (QDs) are highly fluorescent nanoscale crystals with size-dependent emission spectra. Due to their excellent photophysical properties, QDs are a promising alternative to organic fluorescent dyes and fluorescent proteins for cell targeting, imaging, and drug delivery. For biomedical applications, QDs should be chemically modified to be stable in aqueous solutions and tagged with the recognition molecules or drugs. Here, we review surface modification approaches to, and strategies for, conjugation of bioactive molecules with QDs. There are a variety of methods of QD surface modification and QD incorporation into larger delivery systems that yield fluorescent nanocarriers from 10 nm to several micrometers. Conjugates of QDs with peptides, proteins, antibodies, oligonucleotides, and small molecules have been used for fluorescent targeting, tracking, and imaging both in vitro and in vivo. Due to an extremely high stability to photobleaching, QDs were used for long-term visualization. QD applications pave the way for new generations of ultrasensitive detection, diagnostic systems, as well as drug delivery approaches, combining accurate targeting, delivery, and imaging in a single assay.

Arguably targeting is one of the biggest problems for controlled drug delivery. In the case that drugs can be directed with high efficiency to the target tissue, side effects of medication are drastically reduced. Colloidal inorganic nanoparticles (NPs) have been proposed and described in the last 10years as new platforms for in vivo delivery. However, though NPs can introduce plentiful functional properties (such as controlled destruction of tissue by local heating or local generation of free radicals), targeting remains an issue of intense research efforts. While passive targeting of NPs has been reported (the so-called enhanced permeation and retention, EPR effect), still improved active targeting would be highly desirable. One classical approach for active targeting is mediated by molecular recognition via capture molecules, i.e. antibodies (Abs) specific for the target. In order to apply this strategy for NPs, they need to be conjugated with Abs against specific biomarkers. Though many approaches have been reported in this direction, the controlled bioconjugation of NPs is still a challenge. In this article the strategies of controlled bioconjugation of NPs will be reviewed giving particular emphasis to the following questions: 1) how can the number of capture molecules per NP be precisely adjusted, and 2) how can the Abs be attached to NP surfaces in an oriented way. Solution of both questions is a cornerstone in controlled targeting of the inorganic NPs bioconjugates., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The principal methods for the synthesis of highly luminescent core-shell colloidal quantum dots (QDs) of the most widely used CdSe, CdS, ZnSe, and other A(II) B(VI) nanocrystals are reviewed. One-pot versus multistage core synthesis approaches are discussed. The noninjection one-pot method ensures slow, controllable growth of core nanocrystals starting from magic-size seed recrystallization, which yields defect-free cores with strictly specified sizes and shapes and a high monodispersity. Subsequent injection of shell precursors allows the formation of gradient core-shell QDs with a smooth potential barrier for electrons and holes, without strains or interfacial defects, and, as a consequence, a luminescence quantum yield (QY) approaching 100%. These general approaches can also be applied to semiconductor core-shell QDs other than A(II) B(VI) ones to cover the broad spectral range from the near-UV to IR regions of the optical spectrum, thus displacing fluorescent organic dyes from their application areas., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The development and study of nano-bio hybrid materials engineered from membrane proteins (the key functional elements of various biomembranes) and nanoheterostructures (inorganic colloidal nanoparticles, transparent electrodes, and films) is a rapidly growing field at the interface of materials and life sciences. The mainspring of the development of bioinspired materials and devices is the fact that biological evolution has solved many problems similar to those that humans are attempting to solve in the field of light-harvesting and energy-transferring inorganic compounds. Along this way, bioelectronics and biophotonics have shown considerable promise. A number of proteins have been explored in terms of bioelectronic device applications, but bacteriorhodopsin (bR, a photosensitive membrane protein from purple membranes of the bacterium Halobacterium salinarum) and bacterial photosynthetic reaction centres have received the most attention. The energy harvesting in plants has a maximum efficiency of 5%, whereas bR, in the absence of a specific light-harvesting system, allows bacteria to utilize only 0.1-0.5% of the solar light. Recent nano-bioengineering approaches employing colloidal semiconductor and metal nanoparticles conjugated with biosystems permit the enhancement of the light-harvesting capacity of photosensitive proteins, thus providing a strong impetus to protein-based device optimisation. Fabrication of ultrathin and highly oriented films from biological membranes and photosensitive proteins is the key task for prospective bioelectronic and biophotonic applications. In this review, the main advances in techniques of preparation of such films are analyzed. Comparison of the techniques for obtaining thin films leads to the conclusion that the homogeneity and orientation of biomembrane fragments or proteins in these films depend on the method of their fabrication and increase in the following order: electrophoretic sedimentation < Langmuir-Blodgett and Langmuir-Schaefer methods < self-assembly and layer-by-layer methods. The key advances in the techniques of preparation of the assemblies or complexes of colloidal nanocrystals with bR, purple membranes, or photosynthetic reaction centres are also reviewed. Approaches to the fabrication of the prototype photosensitive nano-bio hybrid materials with advanced photovoltaic, energy transfer, and optical switching properties and future prospects in this field are analyzed in the concluding part of the review., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The interaction of proteins in living cells is one of the key processes in the maintenance of their homeostasis. Introduction of additional agents into the chain of these interactions may influence homeostatic processes. Recent advances in nanotechnologies have led to a wide use of nanoparticles (NPs) in industrial and biomedical applications. NPs are small enough to enter almost all compartments of the body, including cells and organelles, and to complicate the pattern of protein interactions. In some cases, interaction of nanoscale objects with proteins leads to hazardous consequences, such as abnormal conformational changes leading to exposure of cryptic peptide epitopes or the appearance of abnormal functions caused by structural modifications. In addition, the high local protein concentration resulting from protein adsorption on NPs may provoke avidity effects arising from close spatial repetition of the same protein. Finally, the interaction of NPs with proteins is known to induce cooperative effects, such as promotion or inhibition of protein fibrillation or self-assembling of NPs on macromolecules serving as a template. It is obvious that better understanding of the molecular mechanisms of nano-bio interactions is crucial for further advances in all nanotechnological applications. This review summarizes recent progress in understanding the molecular mechanisms of the interactions between proteins or peptides and NPs in order to predict the structural, functional, and/or nanotoxic consequences of these interactions.

The occurrence of metastases is one of the main causes of death in many cancers and the main cause of death for breast cancer patients. Micrometastases of disseminated tumour cells and circulating tumour cells are present in more than 30% of breast cancer patients without any clinical or even histopathological signs of metastasis. Low abundance of these cell types in clinical diagnostic material dictates the necessity of their enrichment prior to reliable detection. Current micrometastases detection techniques are based on immunocytochemical and molecular methods suffering from low efficiency of tumour cells enrichment and observer-dependent interpretation. The use of highly fluorescent semiconductor nanocrystals, also known as "quantum dots" and nanocrystal-encoded microbeads tagged with a wide panel of antibodies against specific tumour markers offers unique possibilities for ultra-sensitive micrometastases detection in patients' serum and tissues. The nanoparticle-based diagnostics provides an opportunity for highly sensitive parallel quantification of specific proteins in a rapid and low-cost method, thereby providing a link between the primary tumour and the micrometastases for early diagnosis.

Bead-based assays on very large numbers of molecules in proteomics, genomics, drug screening and clinical diagnostics require encoding of each of the microbeads according to the particular ligand bound to its surface. The benefits of using optically encoded microbeads (instead of the solid-state two-dimensional arrays) are derived from the freedom of bead to move in three dimensions. Polymeric beads optically encoded with organic dyes allow for a limited number of unique codes whereas the use of semiconductor nanocrystals as fluorescent tags improves the beads multiplexed imaging capabilities, photostability and sensitivity of the antigen detection. Additionally, an employment of the recently demonstrated Förster resonance energy transfer (FRET) from the microbeads nanocrystal codes to the nearby antibody dye label allows for the very specific detection of the interaction between the microbead and the antibody. This interaction turns the fluorescence signal from dye label off and on thus effectively discriminating between the occurrence and the non-occurrence of antibody binding. The absence of fluorescent background from non-interacting with the beads dye-labelled antibodies additionally increases the sensitivity of detection and further facilitates the multiplexing capabilities of nanocrystals-based detection and diagnostics. This paper reviews the state-of-the-art results of development of microbeads optically encoded with the fluorescent nanocrystals "quantum dots" and their applications to proteomics for cancer antigens and autoantibodies imaging and diagnosis.

We use high content cell analysis, live cell fluorescent imaging, and transmission electron microscopy approaches combined with inhibitors of cellular transport and nuclear import to conduct a systematic study of the mechanism of interaction of nonfunctionalized quantum dots (QDs) with live human blood monocyte-derived primary macrophages and cell lines of phagocytic, epithelial, and endothelial nature. Live human macrophages are shown to be able to rapidly uptake and accumulate QDs in distinct cellular compartment specifically to QDs size and charge. We show that the smallest QDs specifically target histones in cell nuclei and nucleoli by a multistep process involving endocytosis, active cytoplasmic transport, and entering the nucleus via nuclear pore complexes. Treatment of the cells with an anti-microtubule agent nocodazole precludes QDs cytoplasmic transport whereas a nuclear import inhibitor thapsigargin blocks QD import into the nucleus. These results demonstrate that the nonfunctionalized QDs exploit the cell's active transport machineries for delivery to specific intranuclear destinations.

Efficient biexciton (BX) photoluminescence (PL) from quantum dots (QDs) paves the way to the generation of entangled photons and related applications. However, the quantum yield (QY) of BX PL is much lower than that for single excitons (EX) due to efficient Auger‐like recombination. In the vicinity of plasmon nanoparticles, the recombination rates of EX and BX may be affected by the Purcell effect, fluorescence quenching, and the excitation rate enhancement. Here, the effect of the plasmon resonance spectral position on the EX and BX PL is experimentally studied in two cases: when the plasmon band overlaps with the excitation wavelength and when it coincides with the QDs PL band. In the first case, the EX and BX excitation efficiencies are significantly increased but the EX QY reduced. As a result, the BX‐to‐EX QY ratio is higher than 1 at plasmon–exciton systems separations shorter than 40 nm. In the second case, the radiative recombination rates are enhanced by several orders of magnitude, which led to an increase in BX QY over distances of up to 90 nm. Finally, these two effects are obtained in the same hybrid structure, with the resultant increase in both excitation efficiency and QY of BX PL. [ABSTRACT FROM AUTHOR]

Photoconductivity of thin layers prepared by spin coating of blends of CdSe quantum dots (QDs) and a low-band-gap polymer PCDTBT or PTB7 has been studied. It has been found that photocurrent in the composites containing QDs of 10-nm in size is significantly higher than in those of containing 5-nm QDs. Analysis of the results showed that the photoresponse of the thin layers is mainly determined by the relative positions of the frontier energy levels of the materials used, organic semiconductors and QDs. Therefore, the ability to tune the relative positions of these levels by varying the QD size is of special importance, thus allowing the optimization of photodetectors and photovoltaic cells. [ABSTRACT FROM AUTHOR]

The development of new hybrid materials that can be integrated into current technologies is one of the most important challenges facing material scientists today. The purpose of this work is to review recent studies in one largely unexplored area of nanobiotechnology: the development of nano-bio hybrid materials that exploit Förster Resonance Energy Transfer (FRET) to enhance the functionalities of technologically promising photosynthetic biomaterials. One of very promising approaches is to employ semiconductor quantum dots having a broad absorption spectrum as nanoantennae coupled with the natural light-harvesting complexes of photosynthetic reaction centers. This system reveals great potential for the utilization of quantum dots in artificial photosynthetic devices. The second very useful functionality, which is discussed in this review, is the possibility to enhance the efficiency of the main biological function (proton pumping) of the protein bacteriorhodopsin using nonradiative energy transfer from quantum dots. Also recent studies revealed that FRET-based improvement of the biological function of bacteriorhodopsin in the presence of quantum dots allows for strong wavelength-dependent enhancement of the nonlinear refractive index of bacteriorhodopsin. These new hybrid bio-nanomaterials with exceptional light-harvesting and nonlinear properties will have numerous photonic applications employing their photochromic, energy transfer, and energy conversion properties. [ABSTRACT FROM AUTHOR]

Strong exciton–plasmon interaction enables effective control of the photonic properties of hybrid organic–inorganic nanostructures encompassing light absorption, scattering and luminescence. Whereas the manifestations of light-matter interactions in the absorption and scattering are reasonably well understood their relation to the luminescence as well as luminescence properties themselves in strongly coupled plexcitonic hybrids is still largely underexplored especially for a system with a complex mechanism of hybridisation of states. Here we report on investigation of the interaction between localized and hybridized plasmons in gold nanostars and excitons in J-aggregates under ambient conditions. Our findings demonstrate the quality performance of the formed plexciton system with multiple hybridization channels in terms of the parameters of strong coupling, such as Rabi splitting (230 meV), coupling-strength-to-transition energy ratio (0.07), and cooperativity (2.03). The results of time-resolved experiments elucidate the observed enhanced spontaneous emission rate with regard to the Purcell effect, whose value was estimated from the extinction spectra of the strongly coupled plexciton system. [Display omitted] • Hybrid structures of Au nanostars and J-aggregates of organic dye were prepared by self-assembly. • The interaction between plasmons and excitons is studied using optical spectroscopies and luminescence lifetime imaging. • Large values of Rabi splitting, coupling strength and cooperativity indicate achievement of the strong coupling regime. • Enhanced spontaneous emission rate in hybrid nanostructures is observed and analyzed. [ABSTRACT FROM AUTHOR]