Query: Real-time optical imaging using quantum dot and related nanocrystals

Candidate papers:

abstract: Biomedical optical imaging is rapidly evolving because of its desirable features of rapid frame rates, high sensitivity, low cost, portability and lack of radiation. Quantum dots are attractive as imaging agents owing to their high brightness, and photo and bio stability. Here, the current status of in vitro and in vivo real time optical imaging with quantum dots is reviewed. In addition, we consider related nanocrystals based on solid state semiconductors, including upconverting nanoparticles and bioluminescence resonance energy transfer quantum dots. These particles can improve the signal to background ratio for real time imaging largely by suppressing background signal. Although toxicity and biodistribution of quantum dots and their close relatives remain prime concerns for translation to human imaging, these agents have many desirable features that should be explored for medical purposes.
author_names: Nobuyuki Kosaka

Thomas E McCann

Makoto Mitsunaga

Peter L Choyke

Hisataka Kobayashi
title: Real time optical imaging using quantum dot and related nanocrystals.
venue: Nanomedicine
year: 2010

abstract: The surgical management of brain tumors requires the precise localization of tumor tissues within normal brain parenchyma in order to achieve accurate diagnostic biopsy and complete surgical resection. Quantum dots are optical semiconductor nanocrystals that exhibit stable, bright fluorescence. The intravenous injection of quantum dots is accompanied by reticuloendothelial system and macrophage sequestration. Macrophages infiltrate brain tumors and phagocytize intravenously injected quantum dots, optically labeling the tumors. Macrophage mediated delivery of quantum dots to brain tumors may represent a novel technique to label tumors preoperatively. Quantum dots within tumors may be detected with optical imaging and optical spectroscopy tools, providing the surgeon with real time optical feedback during the resection and biopsy of brain tumors.
author_names: M A Popescu

Steven A Toms
title: In vivo optical imaging using quantum dots for the management of brain tumors
venue: Expert review of molecular diagnostics
year: 2006

abstract: Imaging agents and drug carriers are commonly targeted toward cancer cell through functionalization with specific recognition molecules. Quantum dots (QDs) are fluorescent semiconductor nanocrystals whose extraordinary brightness and photostability make them attractive for direct fluorescent labeling of biomolecules or optical encoding of the membranes and cells. Here, we analyse the cytotoxicity of QD encoded microcapsules, validate an approach to the activation of the microcapsule's surface for further functionalization with monoclonal antibody Trastuzumab, a humanized monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) and already in clinical use for the treatment of HER2 positive breast cancer. In addition, we characterize the cell specific targeting activity of the resultant bio conjugate by immunofluorescence assay (IFA) and real time analysis of interaction of the conjugates with live HER2 overexpressing human breast cancer cells. We demonstrate, that encapsulation of QDs into the polymer shell using the layer by layer deposition method yields highly fluorescent polyelectrolyte microcapsules with a homogeneous size distribution and biocompatibility upon in vitro treatment of cancer cells. Carbodiimide surface activation ensures optimal disperse and optical characteristics of the QD encoded microcapsules before antibody conjugation. The prepared conjugates of the microcapsules with cancer specific monoclonal antibody targeting HER2 provide sufficiently sensitive and specific antibody mediated binding of the microcapsules with live cancer cells, which demonstrated their potential as prospective cancer cell targeting agents.
author_names: Galina Nifontova

Fernanda Ramos-Gomes

Maria Baryshnikova

Frauke Alves

Igor R Nabiev

Alyona Sukhanova
title: Cancer Cell Targeting With Functionalized Quantum Dot Encoded Polyelectrolyte Microcapsules
venue: Front. Chem.
year: 2019

abstract: RATIONALE AND OBJECTIVE Deep tissue optical imaging is of particular interest, as the equipment costs are lower than for competing technologies such as MRI. For this purpose, the development of novel contrast agents with near infrared (NIR) fluorescence is especially important. We report on the use of NIR semiconductor nanocrystals in deep tissue in vivo optical imaging. MATERIALS AND METHODS Semiconductor nanocrystals of CdMnTe/Hg were grown in aqueous solution and then coated with bovine serum albumin (BSA) The nanocrystals were approximately 5 nm in diameter and have a broad fluorescence peak in the NIR (770 nm) Nanocrystals were injected either subcutaneously or intravenously into athymic NCR NU/NU and C3H/HENCR MTV mice and then excited with a spatially broad 633 nm source; the resulting fluorescence was captured with a sensitive CCD camera. RESULTS We have demonstrated that the nanocrystals are a useful angiographic contrast agent for vessels surrounding and penetrating a murine squamous cell carcinoma in a C3H mouse. Preliminary assessment of the depth of penetration for excitation and emission was done by imaging a beating mouse heart, both through an intact thorax and after a thoracotomy. The temporal resolution associated with imaging the nanocrystals in circulation has been addressed, and the blood clearance for this contrast agent has also been measured. CONCLUSIONS There was no significant photobleaching or degradation of the nanocrystals after an hour of continuous excitation. The stability of the nanocrystals together with the time resolution of the optical detection makes them particularly attractive candidates for pharmacokinetic imaging studies.
author_names: Nicole Y Morgan

Sean J English

Wei Chen

Victor Chernomordik

Angelo Russo

Paul D Smith

Amir Gandjbakhche
title: Real time in vivo non invasive optical imaging using near infrared fluorescent quantum dots.
venue: Academic radiology
year: 2005

abstract: Colloidal quantum dots (cQDs) are now a mature nanomaterial with optical properties customizable through varying size and composition. However, their use in optical devices is limited as they are not widely available in convenient forms such as optical fibers. With advances in polymerization methods incorporating nanocrystals, nanocomposite materials suitable for processing into high quality hybrid active fibers can be achieved. We demonstrate a plastic optical fiber fabrication method which ensures homogeneous dispersion of cQDs within a polymer core matrix. Loading concentrations between 10${11} 10${13} CdSe/CdS cQDs per cm${3} in polystyrene were electronically imaged, confirming only sporadic sub wavelength aggregates. Rayleigh scattering losses are therefore dominant at energies below the semiconductors' band gap, but are overtaken by a sharp CdS related absorption onset around 525 nm facilitating cQD excitation. The redshifted photoluminescence emission is then minimally reabsorbed along the fiber with a spectrum barely affected by the polymerization and a quantum yield staying at \sim$65$ of its initial value. The latter, along with the glass transition temperature and refractive index, is independent of the cQD concentration hence yielding a proportionally increasing light output. Our cQD doped fibers are photostable to within 5$ over days showing great promise for functional material applications.
author_names: Carly Whittaker

Arthur Perret

Charles W Fortier

Olivier Tardif

Sebastien A Lamarre

Steeve Morency

Dominic Lariviere

Luc Beaulieu

Younes Messaddeq
title: Light Generating CdSe/CdS Colloidal Quantum Dot Doped Plastic Optical Fibers
year: 2020

abstract: Despite broad applications of quantum dots (QDs) in vitro, severe toxicity and dominant liver uptake have limited their clinical application. QDs that excite and emit in the ultraviolet and visible regions have limited in vivo applicability due to significant optical interference exerted by biological fluids and tissues. Hence we devised a new biocompatible hybrid fluorophore composed of near infrared emitting PbSe quantum dots encapsulated in solid fatty ester nanoparticles (QD FEN) for in vivo imaging. The quantum yield and tissue penetration depth of the QD FEN were characterized, and their biological fate was examined in a breast tumor bearing animal model. It was found for the first time that chemical modification of the headgroup of QD encapsulating organic fatty acids was a must as these groups quenched the photoluminescence of PbSe nanocrystals. The use of fatty esters enhanced aqueous quantum yields of PbSe QDs up to ~45% which was 50% higher than that of water soluble PbSe nanocrystals in an aqueous medium. As a result, a greater than previously reported tissue penetration depth of fluorescence was recorded at 710 nm/840 nm excitation/emission wavelengths. The QD FEN had much lower short term cytotoxicity compared to nonencapsulated water soluble QDs. More importantly, reduced liver uptake, increased tumor retention, lack of toxic response, and nearly complete clearance of QD FEN from the tested animals was demonstrated. With a combination of near infrared spectral properties, enhanced optical properties,and significantly improved biosafety profile, this novel hybrid nanoparticulate fluorophore system demonstrably provides real time, deep tissue fluorescent imaging of live animals, laying a foundation for further development toward clinical application.
author_names: Adam J Shuhendler

Preethy Prasad

Ho-Ka Carol Chan

Claudia Regina Gordijo

Behrouz Soroushian

Michael C Kolios

Kui Yu

Peter James O'Brien

Andrew M Rauth

Xiao Yu Wu
title: Hybrid quantum dot fatty ester stealth nanoparticles: toward clinically relevant in vivo optical imaging of deep tissue.
venue: ACS nano
year: 2011

abstract: Quantum dots (QDs) are highly fluorescent nanocrystals with advanced photophysical and spectral properties: high brightness and stability against photobleaching accompanied by broad excitation and narrow emission spectra. Water soluble QDs functionalized with biomolecules, such as proteins, peptides, antibodies, and drugs, are used for biomedical applications. The advantages of QD based approaches to immuno histochemical analysis, single molecule tracking, and in vivo imaging (over traditional methods with organic dyes and fluorescent proteins) are explained. The unique spectral properties of QDs offer opportunities for designing systems for multiplexed analysis by multicolor imaging for the simultaneous detection of multiple targets. Conjugation of drug molecules with QDs or their incorporation into QD based drug delivery particles makes it possible to monitor real time drug tracking and carry out image guided therapy. Because of the tunability of their photophysical properties, QDs emitting in the near infrared have become an attractive tool for deep tissue mono and multiphoton in vivo imaging. We review recent achievements in QD applications for bioimaging, targeting, and drug delivery, as well as challenges related to their toxicity and non biodegradability. Key and perspectives for further development of advanced QD based nanotools are addressed.
author_names: Regina Bilan

Igor R Nabiev

Alyona Sukhanova
title: Quantum Dot Based Nanotools for Bioimaging, Diagnostics, and Drug Delivery
venue: Chembiochem a European journal of chemical biology
year: 2016

abstract: Two color emitting colloidal semiconductor nanocrystals (NCs) are of interest for applications in multimodal imaging, sensing, lighting, and integrated photonics. Dual color emission from core and shell related optical transitions has been recently obtained using so called dot in bulk (DiB) CdSe/CdS NCs comprising a quantum confined CdSe core embedded into an ultrathick ~7 9 nm) CdS shell. The physical mechanism underlying this behavior is still under debate. While a large shell volume appears to be a necessary condition for dual emission, comparison between various types of thick shell CdSe/CdS NCs indicates a critical role of the interface "sharpness" and the presence of potential barriers. To elucidate the effect of the interface morphology on the dual emission, we perform side by side studies of CdSe/CdS DiB NCs with nominally identical core and shell dimensions but different structural properties of the core/shell interface arising from the crystal structure of the starting CdSe cores (zincblende vs wurtzite) While both structures exhibit dual emission under comparable pump intensities, NCs with a zincblende core show a faster growth of shell luminescence with excitation fluence and a more readily realized regime of amplified spontaneous emission (ASE) even under "slow" nanosecond excitation. These distinctions can be linked to the structure of the core/shell interface: NCs grown from the zincblende cores contain a ~3.5 nm thick zincblende CdS interlayer, which separates the core from the wurtzite CdS shell and creates a potential barrier for photoexcited shell holes inhibiting their relaxation into the core. This helps maintain a higher population of shell states and simplifies the realization of dual emission and ASE involving shell based optical transitions.
author_names: Valerio Pinchetti

Francesco Meinardi

Andrea Camellini

Gianluca Sirigu

Sotirios Christodoulou

Wan Ki Bae

Francesco De Donato

Liberato Manna

Margherita Zavelani-Rossi

Iwan Moreels

Victor I Klimov

Sergio Brovelli
title: Effect of Core/Shell Interface on Carrier Dynamics and Optical Gain Properties of Dual Color Emitting CdSe/CdS Nanocrystals.
venue: ACS nano
year: 2016

abstract: Water dispersible 1 thioglycerol (TG) capped Mn doped ZnS quantum dots were prepared in aqueous solution using the nucleation doping strategy. Using 4% Mn relative to Zn and a Zn(OAc)2/Na2S ratio of 0.9, Mn:ZnS nanocrystals with an average diameter of 3.9 0.5 nm, with pure Mn2+ related photoluminescence (PL) at 585 nm, and with a PL quantum yield of 13.2% were obtained. Transmission electron microscopy, X ray powder diffraction, electron spin resonance, X ray photoelectron spectroscopy, UV visible spectroscopy and spectrofluorometry have been used to characterize the crystal structure, the doping status, and the optical properties of the doped dots. Folic acid (FA) was linked to TG capped Mn:ZnS nanocrystals to produce Mn:ZnS@TG FA nanobioconjugates that were used for targeted in vitro delivery to a human cancer cell line. Folate receptor mediated cellular uptake of FA functionalized dots is proven via confocal and two photon imaging.
author_names: Malgorzata Geszke-Moritz

Hanna Piotrowska

Marek Murias

Lavinia Balan

Michal Moritz

Janina Lulek

Raphael Schneider
title: Thioglycerol capped Mn doped ZnS quantum dot bioconjugates as efficient two photon fluorescent nano probes for bioimaging.
venue: Journal of materials chemistry. B
year: 2013

abstract: Quantum dots (QDs) are light emitting semi conductor nanocrystals with novel optical properties including superior photostability, narrow emission spectra with continuous excitation spectra. These properties make QDs especially suitable for multiplexed fluorescent labeling, live cell imaging, and in vivo animal imaging. The multiplexing potential has been recognized but real applications of biological/clinical significance are few. In this study, we used quantum dots to study epithelial mesenchymal transition (EMT) an important process involved in the bone metastasis of prostate cancer. Two prostate cancer cells lines with distinct molecular profiles, representing the two ends of the EMT process, were selected for this study. Four EMT related biomarkers including E cadherin, N cadherin, Vimentin, and RANKL were stained with QD antibody conjugates with elongation factor 1alpha as the internal control. Morphological information of the QD stained cells was obtained by digital color imaging and quantitative information obtained by spectra analysis using a spectrometer. Two types of analysis were performed: abundance of each biomarker in the same cell line relative to the internal control; and the relative abundance of these markers between the two cell lines. Our results demonstrate the feasibility of QDs for multiplexed profiling of FFPE cells/tissue of clinical significance; however, the standardization and quantification still awaits optimization.
author_names: Yun Xing

Takeo Numora

Leland W K Chung

Haiyen E Zhau

Shuming Nie
title: Multiplexed molecular profiling of prostate cancer specimens using semiconductor quantum dot bioconjugates
venue: SPIE BiOS
year: 2007