Delivering quantum dots into cells: strategies, progress and remaining issues (original) (raw)

Bioconjugated quantum dots for in vivo molecular and cellular imaging☆

Advanced Drug Delivery Reviews, 2008

Semiconductor quantum dots (QDs) are tiny light-emitting particles on the nanometer scale, and are emerging as a new class of fluorescent labels for biology and medicine. In comparison with organic dyes and fluorescent proteins, they have unique optical and electronic properties, with size-tunable light emission, superior signal brightness, resistance to photobleaching, and broad absorption spectra for simultaneous excitation of multiple fluorescence colors. QDs also provide a versatile nanoscale scaffold for designing multifunctional nanoparticles with both imaging and therapeutic functions. When linked with targeting ligands such as antibodies, peptides or small molecules, QDs can be used to target tumor biomarkers as well as tumor vasculatures with high affinity and specificity. Here we discuss the synthesis and development of state-of-the-art QD probes and their use for molecular and cellular imaging. We also examine key issues for in vivo imaging and therapy, such as nanoparticle biodistribution, pharmacokinetics, and toxicology.

Quantum dots in imaging, drug delivery and sensor applications

International Journal of Nanomedicine

Quantum dots (QDs), also known as nanoscale semiconductor crystals, are nanoparticles with unique optical and electronic properties such as bright and intensive fluorescence. Since most conventional organic label dyes do not offer the near-infrared (.650 nm) emission possibility, QDs, with their tunable optical properties, have gained a lot of interest. They possess characteristics such as good chemical and photo-stability, high quantum yield and size-tunable light emission. Different types of QDs can be excited with the same light wavelength, and their narrow emission bands can be detected simultaneously for multiple assays. There is an increasing interest in the development of nano-theranostics platforms for simultaneous sensing, imaging and therapy. QDs have great potential for such applications, with notable results already published in the fields of sensors, drug delivery and biomedical imaging. This review summarizes the latest developments available in literature regarding the use of QDs for medical applications.

Quantum Dots: A New-fangled Loom in Drug Delivery and Therapeutics

Quantum dots (QDs) are luminescent nanoscale semiconductor crystal with surface chemistry and unique optical properties that make them useful as carriers for traceable targeted delivery and therapeutic applications. QDs combines with cancer specific ligands, antibodies and peptides etc., and were found to be more effective for identifying and imaging human cancerous cells. The present review gives an exhausted account of QDs including the synthesis, properties, toxicity and their optical and electrochemical applications in drug delivery and therapeutics. Moreover, special emphasis is given on QDs applicability in biomedicine, cancer diagnosis and therapy.

Biofunctional quantum dots as fluorescence probe for cell-specific targeting

Colloids and Surfaces B: Biointerfaces, 2014

We describe here the synthesis, characterization, bioconjugation, and application of water-soluble thioglycolic acid TGA-capped CdTe/CdS quantum dots (TGA-QDs) for targeted cellular imaging. Antihuman epidermal growth factor receptor 2 (HER2) antibodies were conjugated to TGA-QDs to target HER2-overexpressing cancer cells. TGA-QDs and TGA-QDs/anti-HER2 bioconjugates were characterized by fluorescence and UV-Vis spectroscopy, X-ray diffraction (XRD), hydrodynamic sizing, electron microscopy, and gel electrophoresis. TGA-QDs and TGA-QDs/anti-HER2 were incubated with cells to examine cytotoxicity, targeting efficiency, and cellular localization. The cytotoxicity of particles was measured using an MTT assay and the no observable adverse effect concentration (NOAEC), 50% inhibitory concentration (IC 50 ), and total lethal concentration (TLC) were calculated. To evaluate localization and targeting efficiency of TGA-QDs with or without antibodies, fluorescence microscopy and flow cytometry were performed. Our results indicate that antibody-conjugated TGA-QDs are well-suited for targeted cellular imaging studies.

Quantum dots for biomedical applications

Expert opinion on medical diagnostics, 2008

Nanotechnology is an emerging field that could have a significant impact on cancer diagnosis, treatment and analysis. Quantum dots represent one of the most interesting nanotechnology-based platforms, and their unique properties make them a potentially versatile tool for molecular diagnostics. Here, the most promising uses of quantum dots for translational research are reviewed, ranging from multiplexed immunofluorescence, targeted drug delivery coupled with disease visualization, tumor and sentinel organs localization and long-term cell tracing. Finally, potential future directions for quantum dots as both a diagnostic and therapeutic tool in biomedical research will be explored. The use of quantum dots in biomedical applications is accelerating owing to their unique physical attributes, imaging capabilities, and potential for therapeutic delivery.

Quantum dots for in vivo molecular and cellular imaging

Methods in molecular biology (Clifton, N.J.), 2007

Multifunctional nanoparticle probes based on semiconductor quantum dots (QDs) are developed for simultaneous targeting and imaging of cancer cells in living animals. The structural design involves encapsulating luminescent QDs with an ABC triblock copolymer, and linking this polymer to tumor-targeting ligands, such as antibodies and drug-delivery functionalities. In vivo targeting studies of human prostate cancer growing in nude mouse show that the QD probes can be delivered to tumor sites by both enhanced permeation and retention (passive targeting) and by antibody binding to cancer-specific cell surface biomarkers such as prostate-specific membrane antigen (active targeting). Using both subcutaneous injection of QD-tagged cancer cells and the systemic injection of multifunctional QD probes, multicolor fluorescence imaging of as few as 10-100 cancer cells can be achieved under in vivo conditions. The use of spectrally resolved imaging can efficiently remove autofluorescence backgro...

Biomedical Applications of Quantum Dots: Overview, Challenges, and Clinical Potential

International Journal of Nanomedicine, 2022

Despite the massive advancements in the nanomedicines and their associated research, their translation into clinicallyapplicable products is still below promises. The latter fact necessitates an in-depth evaluation of the current nanomedicines from a clinical perspective to cope with the challenges hampering their clinical potential. Quantum dots (QDs) are semiconductors-based nanomaterials with numerous biomedical applications such as drug delivery, live imaging, and medical diagnosis, in addition to other applications beyond medicine such as in solar cells. Nevertheless, the power of QDs is still underestimated in clinics. In the current article, we review the status of QDs in literature, their preparation, characterization, and biomedical applications. In addition, the market status and the ongoing clinical trials recruiting QDs are highlighted, with a special focus on the challenges limiting the clinical translation of QDs. Moreover, QDs are technically compared to other commercially-available substitutes. Eventually, we inspire the technical aspects that should be considered to improve the clinical fate of QDs.

Quantum Dot: Novel Carrier for Drug Delivery

Quantum dots are nanoscale semiconductor crystals ranging typically between 1-10 nanometers and have capacity to glow or fluorescence brightly when excited by a light source such as a laser. Quantum dots are tiny bits of microscopic metal, thousand times smaller than width of a hair or semiconductor boxes such as cadmium selenide-zinc sulphide. Quantum dots are emerging as a new class of fluorescent probes for biomolecular and cellular imaging. The nature of this technology makes it suitable for application such as in-vivo imaging including live cell and whole animal imaging, blood cancer assay, cancer detection and treatment. With a focus on the use of quantum dots this review includes a detailed examination of quantum dot, their synthesis, properties and applications, toxic effects, use in imaging and analysis plus quantum dot drug delivery systems.

Cytotoxicity of Quantum Dots Used for In Vitro Cellular Labeling: Role of QD Surface Ligand, Delivery Modality, Cell Type, and Direct Comparison to Organic Fluorophores

Bioconjugate Chemistry

Interest in taking advantage of the unique spectral properties of semiconductor quantum dots (QDs) has driven their widespread use in biological applications such as in vitro cellular labeling/imaging and sensing. Despite their demonstrated utility, concerns over the potential toxic effects of QD core materials on cellular proliferation and homeostasis have persisted, leaving in question the suitability of QDs as alternatives for more traditional fluorescent materials (e.g., organic dyes, fluorescent proteins) for in vitro cellular applications. Surprisingly, direct comparative studies examining the cytotoxic potential of QDs versus these more traditional cellular labeling fluorophores remain limited. Here, using CdSe/ZnS (core/shell) QDs as a prototypical assay material, we present a comprehensive study in which we characterize the influence of QD dose (concentration and incubation time), QD surface capping ligand and delivery modality (peptide or cationic amphiphile transfection r...

Quantum Dots: An Optimistic Approach to Novel Therapeutics

Nanotechnology is a multidisciplinary field and has achieved breakthroughs in bioengineering, molecular biology, diagnostics, and therapeutics. Targeted delivery of therapeutic agents has the potential to localize drugs to a specific tissue as a mechanism to enhance treatment efficacy and abrogate side effects. The successful nanoparticle mediated delivery includes the ability to target specific tissues and cell types (primary & secondary targeting) and escape from the uptake by the reticuloendothelial system (RES). The feasibility of in vivo targeting of peptides has recently been achieved by using semiconductor quantum dots (Qdots). Qdots are small (<10 nm) inorganic nanocrystals that possess unique luminescent properties; their fluorescence emission is stable and tuned by varying the particle size or composition. It has been found that ZnS-capped CdSe Qdots coated with a lung-targeting peptide accumulate in the lungs of mice after i.v. injection, whereas two other peptides specifically direct Qdots to blood vessels or lymphatic vessels in tumors. Adding polyethylene glycol to the Qdot coating slows down opsonization and prevents nonselective accumulation of Qdots in RES. These results encourage the construction of more complex nanostructures with capabilities such as disease sensing and feedback regulated drug delivery. This work is expected to address the formidable challenges encountered in the field of drug targeting, and opens up new vistas in future development of a promisingly active and site-specific delivery system.