Quantum dots in cancer therapy

INTRODUCTION: Quantum dots (QDs) are nanometer-size luminescent semiconductor nanocrystals. Their unique optical properties, such as high brightness, long-term stability, simultaneous detection of multiple signals and tunable emission spectra, make them appealing as potential diagnostic and therapeutic systems in the field of oncology. AREAS COVERED: This paper summarizes the recent progress of promising applications of QDs in cancer therapy, from the following aspects: identifying molecular targets, sentinel lymph-node mapping, surgical oncology, drug delivery and tracking, fluorescence resonance energy transfer and photodynamic therapy, personalized and predictive medicine, and multifunctional design and development. Limitations and toxicity issues related to QDs in living organisms are also discussed. EXPERT OPINION: Bioconjugated QDs can be used to identify potential molecular biomarkers for cancer diagnosis, treatment and prognosis. They may allow the surgeon to map sentinel lymph nodes and perform a complete surgical resection. Their unique optical properties make them ideal donors of fluorescence resonance energy transfer and photodynamic therapy studies. Multifunctional QDs have become effective materials for synchronous cancer diagnosis, targeting and treatment. For QDs, toxicity remains the major barrier to clinical translation.     

Targeted multifunctional lipid-based nanocarriers for image-guided drug delivery

Lipid-based nanocarriers have proven successful in the delivery of mainly chemotherapeutic agents, and currently they are being applied clinically in the treatment of various types of cancer. These drug delivery systems achieve increased therapeutic efficacy by altering the pharmacokinetics and biodistribution of encapsulated drugs, resulting in decreased drug toxicity and enhanced accumulation in tumor tissue. This increased accumulation is due to the relatively leaky immature vasculature of a tumor. After the clinical relevance of such drug delivery systems was demonstrated, research in this area focused on optimization, both by cell specific targeting and including controlled and triggered release concepts within the carrier. These more advanced targeted nanocarriers in general have clearly shown their potential in various animal tumor models and await clinical application. The development of targeted nanocarriers in which therapeutic and imaging agents are merged into a single carrier will certainly be of importance in the near future. Indeed, scientists active in the field of imaging (e.g. nuclear and magnetic resonance imaging) have already started to exploit nanocarriers for molecular imaging. Image-guided drug delivery using these multifunctional nanocarriers, containing therapeutic and imaging agents, will ultimately allow for online monitoring of tumor location, tumor targeting levels, intratumoral localization and drug release kinetics prior and during radio- and/or chemotherapeutic treatment. This review describes the current status and challenges in the field of nanocarrier-aided drug delivery and drug targeting and discusses the opportunities of combining imaging probes with these drug carriers and the potential of these multifunctional lipid-based nanocarriers within image-guided drug delivery.     

Folate-targeting magnetic core-shell nanocarriers for selective drug release and imaging

One of the most urgent medical requirements for cancer diagnosis and treatment is how to construct a multifunctional vesicle for simultaneous diagnostic imaging and therapeutic applications. In our study, superparamagnetic iron oxide nanocrystals (SPIONs) and doxorubicin hydrochloride (DOX) are co-encapsulated into PLGA/polymeric liposome core-shell nanocarriers for achieving simultaneous magnetic resonance imaging and targeting drug delivery. The core-shell nanocarrier was self-assembled from a hydrophobic PLGA core and a hydrophilic folate coated PEGlated lipid shell. The experiment showed that folate-targeting magnetic core-shell nanocarriers show clear core-shell structure, excellent magnetism and controlled drug release behavior. Importantly, the core-shell nanoparticles achieve the possibility of co-delivering drugs and SPIONs to the same cells for enhancing magnetic resonance imaging (MRI) effect and improving drug delivery efficiency simultaneously. Our data suggests that the folate-targeting magnetic core-shell nanocarriers (FMNs) could provide effective cancer-targeting and MRI as well as drug delivery. The FMNs may become a useful nanomedical carrier system for cancer diagnosis and treatment.     

Quantum dots in cancer therapy

Introduction: Quantum dots (QDs) are nanometer-size luminescent semiconductor nanocrystals. Their unique optical properties, such as high brightness, long-term stability, simultaneous detection of multiple signals and tunable emission spectra, make them appealing as potential diagnostic and therapeutic systems in the field of oncology.

Areas covered: This paper summarizes the recent progress of promising applications of QDs in cancer therapy, from the following aspects: identifying molecular targets, sentinel lymph-node mapping, surgical oncology, drug delivery and tracking, fluorescence resonance energy transfer and photodynamic therapy, personalized and predictive medicine, and multifunctional design and development. Limitations and toxicity issues related to QDs in living organisms are also discussed.

Expert opinion: Bioconjugated QDs can be used to identify potential molecular biomarkers for cancer diagnosis, treatment and prognosis. They may allow the surgeon to map sentinel lymph nodes and perform a complete surgical resection. Their unique optical properties make them ideal donors of fluorescence resonance energy transfer and photodynamic therapy studies. Multifunctional QDs have become effective materials for synchronous cancer diagnosis, targeting and treatment. For QDs, toxicity remains the major barrier to clinical translation.     

Multifunctional silica nanoparticles for targeted delivery of hydrophobic imaging and therapeutic agents

This article reports the development of a multifunctional silica nanoparticle system for targeted delivery of hydrophobic imaging and therapeutic agents. Normally, silica nanoparticles have been widely used to deliver hydrophilic drugs such as doxorubicin while difficult to carry hydrophobic drugs. A strategy for loading hydrophobic drugs onto silica nanoparticles via covalent attachment was developed in this study as a universal strategy to solve this problem. Docetaxel, one of the most potent therapeutics for cancer treatment is selected as a model hydrophobic drug and quantum dots (QDs) are used as a model imaging agent. Such a multifunctional delivery system possesses high drug loading capacity, controlled drug release behavior and stable drug reservation. A mixed layer of polyethylene glycol conjugated phospholipids is formed on the nanoparticle surface to further enhance the biocompatibility and cell fusion capability of the delivery system. Folic acid as ligand is then conjugated onto the surface layer for targeting. Such a multifunctional system for targeting, imaging and therapy is characterized and evaluated in vitro. Fluorescent confocal microscopy is used to monitor the cellular uptake by specific cancer cells. Cytotoxicity studies are conducted by using MTT assay.     

Multimodal imaging of dendritic cells using a novel hybrid magneto-optical nanoprobe

A transfecting agent-coated hybrid imaging nanoprobe (HINP) composed of visible and near-infrared (NIR) light emitting quantum dots (QDs) tethered to superparamagnetic iron oxide (SPIO) nanoparticles was developed. The surface modification of QDs and SPIO particles and incorporation of dual QDs within the SPIO were characterized by dynamic light scattering (DLS), quartz crystal microbalance (QCM) analysis and atomic force microscopy (AFM). The optical contrasting properties of HINP were characterized by absorption and photoluminescence spectroscopy and fluorescence imaging. Multicolor HINP was used in imaging the migration of dendritic cells (DCs) by optical, two-photon and magnetic resonance imaging techniques. FROM THE CLINICAL EDITOR: The development of a transfecting agent-coated hybrid imaging nanoprobe (HINP) composed of visible and near-infrared light emitting quantum dots (QDs) tethered to superparamagnetic iron oxide nanoparticles is reported in this paper. Multicolor HINP was used in imaging the migration of dendritic cells by optical, two-photon and magnetic resonance imaging techniques.     

Quantiosomes as a Multimodal Nanocarrier for Integrating Bioimaging and Carboplatin Delivery

Purpose

Here we report the development of quantiosomes, niosomes formed from Span 60, cholesterol, and quantum dots (QDs), for achieving sensitive bioimaging and anticancer drug delivery.

Methods

The nanocarriers were further modified by incorporating soy phosphatidylcholine (SPC), polyethylene glycol (PEG), or cationic surfactant to display different efficiencies. Carboplatin was used as the model drug. The cellular uptake, cytotoxicity, and migration inhibition of quantiosomes for treating melanoma cells were described. Finally, intratumoral carboplatin accumulation and in-vivo bioimaging were examined.

Results

The average diameters of quantiosomes ranged between 151 and 173 nm, depending on the composition selected. Approximately 50% of the drug was entrapped in quantiosomes. Electron microscopy confirmed the bilayer structure of quantiosomes and the presence of QDs in the vesicular surface. The nanodispersions showed a significant internalization into cells, especially the cationic formulations. Quantiosomes increased cytotoxicity against melanoma by 3?~?4-fold as compared to free carboplatin. In-vivo intratumoral administration demonstrated an increased drug depot in melanoma from 6 to 10 ng/mg by SPC-loaded and PEGylated quantiosomes relative to aqueous control. In-vivo fluorescence imaging showed that quantiosomes reduced leakage of QDs from melanoma. A fluorescence signal confined in tumors could be sustained for at least 24 h. Quantiosomes also exhibited a sensitive and prolonged fluorescence in ovarian tumors.

Conclusion

Niosomes containing QDs and carboplatin as a multifunctional nanosystems provide a non-expensive and efficient strategy to prolong drug retention and fluorescence signal in tumors.     

A review of nanocarrier-based CNS delivery systems

Drug delivery to the central nervous system (CNS) is one of the most challenging fields of research and development for pharmaceutical and biotechnology products. A number of hydrophilic therapeutic agents, such as antibiotics, anticancer agents, or newly developed neuropeptides do not cross the blood brain barrier (BBB) after systemic administration. The BBB is formed by the tight junctions at the brain capillary endothelial cells, which strictly control drug transfer from blood to brain. Drug modification, osmotic opening of cerebral capillary endothelium, and alternative routes for administration (e.g., intracerebral delivery) have been successfully used to enhance drug transport to the CNS. The use of nanocarriers, such as liposomes and solid polymeric or lipid nanoparticles may be advantageous over the current strategies. These nanocarriers can not only mask the BBB limiting characteristics of the therapeutic drug molecule, but may also protect the drug from chemical/enzymatic degradation, and additionally provide the opportunity for sustained release characteristics. Reduction of toxicity to peripheral organs can also be achieved with these nanocarriers. This review article discusses the various barriers for drug delivery to the CNS and reviews the current state of nanocarriers for enhancing drug transport into the CNS.     

Multifunctional hybrid-carbon nanotubes: new horizon in drug delivery and targeting

Carbon nanotubes (CNTs) have emerged as an intriguing nanotechnological tool for numerous biomedical applications including biocompatible modules for the bioactives delivery ascribed to their unique properties, such as greater loading efficiency, biocompatibility, non-immunogenicity, high surface area and photoluminescence, that make them ideal candidate in pharmaceutical and biomedical science. The design of multifunctional hybrid-CNTs for drug delivery and targeting may differ from the conventional drug delivery system. The conventional nanocarriers have few limitations, such as inappropriate availability of surface-chemical functional groups for conjugation, low entrapment/loading efficiency as well as stability as per ICH guidelines with generally regarded as safe (GRAS) prominences. The multifunctional hybrid-CNTs will sparked and open a new door for researchers, scientist of the pharmaceutical and biomedical arena. This review summarizes the vivid aspects of CNTs like characterization, supramolecular chemistry of CNTs–dendrimer, CNTs–nanoparticles, CNTs–quantum dots conjugate for delivery of bioactives, not discussed so far.     

Nanomedicines for the treatment of rheumatoid arthritis: State of art and potential therapeutic strategies

Increasing understanding of the pathogenesis of rheumatoid arthritis (RA) has remarkably promoted the development of effective therapeutic regimens of RA. Nevertheless, the inadequate response to current therapies in a proportion of patients, the systemic toxicity accompanied by long-term administration or distribution in non-targeted sites and the comprised efficacy caused by undesirable bioavailability, are still unsettled problems lying across the full remission of RA. So far, these existing limitations have inspired comprehensive academic researches on nanomedicines for RA treatment. A variety of versatile nanocarriers with controllable physicochemical properties, tailorable drug release pattern or active targeting ability were fabricated to enhance the drug delivery efficiency in RA treatment. This review aims to provide an up-to-date progress regarding to RA treatment using nanomedicines in the last 5 years and concisely discuss the potential application of several newly emerged therapeutic strategies such as inducing the antigen-specific tolerance, pro-resolving therapy or regulating the immunometabolism for RA treatments.KEY WORDS: Nanomedicines, Rheumatoid arthritis, Targeted drug delivery, Liposome, Micelle, Stimulus-responsive delivery systems, Immune tolerance, Inflammation resolution     

Novel core–shell magnetic nanoparticles for Taxol encapsulation in biodegradable and biocompatible block copolymers: Preparation,characterization and release properties

Theranostic polymeric nanocarriers loaded with anticancer drug Taxol and superparamagnetic iron oxide nanocrystals have been developed for possible magnetic resonance imaging (MRI) use and cancer therapy. Multifunctional nanocarriers with a core–shell structure have been prepared by coating superparamagnetic Fe₃O₄ nanoparticles with block copolymer of poly(ethylene glycol)-b-poly(propylene succinate) with variable molecular weights of the hydrophobic block poly(prolylene succinate). The multifunctional polymer nano-vehicles were prepared using a nanoprecipitation method. Scanning transmission electron microscopy revealed the encapsulation of magnetic nanoparticles inside the polymeric matrix. Energy dispersive X-ray spectroscopy and electron energy loss spectroscopy mapping allowed us to determine the presence of the different material ingredients in a quantitative way. The diameter of the nanoparticles is below 250 nm yielding satisfactory encapsulation efficiency. The nanoparticles exhibit a biphasic drug release pattern in vitro over 15 days depending on the molecular weight of the hydrophobic part of the polymer matrix. These new systems where anti-cancer therapeutics like Taxol and iron oxide nanoparticles (IOs) are co-encapsulated into new facile polymeric nanoparticles, could be addressed as potential multifunctional vehicles for simultaneous drug delivery and targeting imaging as well as real time monitoring of therapeutic effects.     

Quantum dots - nano-sized probes for the exploration of cellular and intracellular targeting.

Nanoparticles emerged as promising tool in drug targeting, since, after appropriate modification, they are able to deliver their payload to specific sites, like tissues, cells, or even certain cellular organelles. In this context, the delivery of nanoparticles from the circulation into the target cells represents a crucial step. Here, model drug delivery systems such as quantum dots are ideal candidates to elucidate this process in more detail, since they provide outstanding features like a small and uniform size, unique optical properties for most sensitive detection and modifiable surfaces. Recent progress in the surface chemistry of quantum dots expanded their use in biological applications, reduced their cytotoxicity and rendered quantum dots a powerful tool for the investigation of distinct cellular processes, like uptake, receptor trafficking and intracellular delivery. In this review, we will not only describe the ideal attributes of QDs for biological applications and imaging but also their distinct specific and non-specific pathways into the cells as well as their intracellular fate.     

PEGylated nanomedicines: recent progress and remaining concerns

Introduction: Recent biopharma deals related to nanocarrier drug delivery technologies highlight the emergence of nanomedicine. This is perhaps an expected culmination of many years of research demonstrating the potential of nanomedicine as the next generation of therapeutics with improved performance. PEGylated nanocarriers play a key role within this field.

Areas covered: The drug delivery advantages of nanomedicines in general are discussed, focusing on nanocarriers and PEGylated nanomedicines, including products under current development/clinical evaluation. Well-established drug delivery benefits of PEGylation (e.g., prolonged circulation) are only briefly covered. Instead, attention is deliberately made to less commonly reported advantages of PEGylation, including mucosal delivery of nanomedicines. Finally, some of the issues related to the safety of PEGylated nanomedicines in clinical application are discussed.

Expert opinion: The advent of nanomedicine providing therapeutic options of refined performance continues. Although PEGylation as a tool to improve the pharmacokinetics of nanomedicines is well established and is used clinically, other benefits of ‘PEGnology', including enhancement of physicochemical properties and/or biocompatibility of actives and/or drug carriers, as well as mucosal delivery, have attracted less attention. While concerns regarding the clinical use of PEGylated nanomedicines remain, evidence suggests that at least some safety issues may be controlled by adequate designs of nanosystems.     

Colloidal nanocarriers: a review on formulation technology,types and applications toward targeted drug delivery

Colloidal nanocarriers, in their various forms, have the possibility of providing endless opportunities in the area of drug delivery. The current communication embodies an in-depth discussion of colloidal nanocarriers with respect to formulation aspects, types, and site-specific drug targeting using various forms of colloidal nanocarriers with special insights to the field of oncology. Specialized nanotechnological approaches like quantum dots, dendrimers, integrins, monoclonal antibodies, and so forth, which have been extensively researched for targeted delivery of therapeutic and diagnostic agents, are also discussed. Nanotechnological patents, issued by the U.S. Patent and Trademark Office in the area of drug delivery, are also included in this review to emphasize the importance of nanotechnology in the current research scenario.From the Clinical EditorColloidal nanocarriers provide almost endless opportunities in the area of drug delivery. While the review mainly addresses potential oncological applications, similar approaches may be applicable in other conditions with a requirement for targeted drug delivery. Technologies including quantum dots, dendrimers, integrins, monoclonal antibodies are discussed, along with US-based patents related to these methods.     

Polymeric nanocarriers for controlled and enhanced delivery of therapeutic agents to the CNS

Polymeric nanocarriers are versatile structures that can be engineered to obtain high drug loading, good delivery yields and tunable release kinetics. Moreover, the particle surface can be modified for selective targeting of organs or tissues. In particular, polymeric nanocarriers can be conjugated with functional groups promoting translocation through the blood-brain barrier, thus providing a promising system to deliver therapeutic agents and/or diagnostic probes to the brain. Here we review recent literature on the preparation and characterization of polymeric nanoparticles as potential agents for drug delivery to the CNS, with an emphasis on materials chemistry and functionalization strategies for improved selectivity and delivery. Finally, we underline the immunotoxicological aspects of this class of nanostructured materials in view of potential clinical applications.     

The future of quantum dots in drug discovery

The rapid development of drug discovery today is inseparable from the interaction of advanced particle technologies and new drug synthesis protocols. Quantum dots (QDs) are regarded as a unique class of fluorescent labels, with unique optical properties such as high brightness and long-term colloidal and optical stability; these are suitable for optical imaging, drug delivery and optical tracking, fluorescence immunoassay and other medicinal applications. More importantly, QD possesses a rich surface chemistry property that is useful for incorporating various drug molecules, targeting ligands, and additional contrast agents (e.g., MRI, PET, etc.) onto the nanoparticle surface for achieving targeted and traceable drug delivery therapy at both cellular and systemic levels. In recent times, the advancement of QD technology has promoted the use of functionalized nanocrystals for in vivo applications. Such research is paving the way for drug discovery using various bioconjugated QD formulations. In this editorial, the authors highlight the current research progress and future applications of QDs in drug discovery.     

Delivery strategies for sustained drug release in the lungs

Drug delivery to the lungs by inhalation offers a targeted drug therapy for respiratory diseases. However, the therapeutic efficacy of inhaled drugs is limited by their rapid clearance in the lungs. Carriers providing sustained drug release in the lungs can improve therapeutic outcomes of inhaled medicines because they can retain the drug load within the lungs and progressively release the drug locally at therapeutic levels. This review presents the different formulation strategies developed to control drug release in the lungs including microparticles and the wide array of nanomedicines. Large and porous microparticles offer excellent aerodynamic properties. Their large geometric size reduces their uptake by alveolar macrophages, making them a suitable carrier for sustained drug release in the lungs. Similarly, nanocarriers present significant potential for prolonged drug release in the lungs because they largely escape uptake by lung-surface macrophages and can remain in the pulmonary tissue for weeks. They can be embedded in large and porous microparticles in order to facilitate their delivery to the lungs. Conjugation of drugs to polymers as polyethylene glycol can be particularly beneficial to sustain the release of proteins in the lungs as it allows high protein loading. Drug conjugates can be readily delivered to respiratory airways by any current nebulizer device. Nonetheless, liposomes represent the formulation most advanced in clinical development. Liposomes can be prepared with lipids endogenous to the lungs and are particularly safe. Their composition can be adjusted to modulate drug release and they can encapsulate both hydrophilic and lipophilic compounds with high drug loading.     

Bioconjugated quantum dots for in vivo molecular and cellular imaging

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.     

基于碳纳米角的荧光标记载药体系的构建、表征及体外释放

目的考察碳纳米角(CNHox)经不同浓度壳聚糖(CS)修饰后在水和磷酸缓冲溶液(PBS)中的分散性;构建以CNHox为载体装载多烯紫杉醇(DTX)并通过CS连接CdTe量子点荧光探针的载药体系;考察载药体系体外药物释放行为。方法测定经不同浓度CS修饰的CNHox在水中和PBS中的zeta电位,静置观察分散液的聚沉情况;饱和溶液结晶法装载DTX,热重法测定载药量;以EDC、NHS为交联剂共价连接CdTe量子点与CS,修饰到载有DTX的CNHox表面,构建新型荧光标记抗肿瘤载药体系,对该载药体系进行系列表征;考察药物体外溶出情况,高效液相色谱法测定溶出DTX的含量,并绘制体外释放曲线。结果 CS浓度达到2.50mg·mL-1时,CNHox在PBS中的分散性良好;CNHox装载DTX载药量可以达到1.170 mg·mg-1;载药体系成功标记荧光量子点,且在PBS中的分散性良好;体外累积药物释放量为54.8%,释放曲线有明显缓释行为。结论 CS修饰可提高CNHox在盐溶液中的分散性;载药体系具有较高载药量;量子点成功标记载药体系,为该载药体系的体外示踪研究奠定基础;该载药体系的体外释放试验证实具有缓释效果。     

Near-infrared imaging of diseases: A nanocarrier approach

Developments in fluorescence imaging, brought popularity to near infrared (NIR) imaging with far-red and NIR fluorophores applied for biosensing and bioimaging in living systems. Noninvasive NIR imaging gained popularity with the use of effective NIR dyes to obtain macroscopic fluorescence images. Several attributes of NIR dyes make them desirable agents, including high specificity, high sensitivity, minimized background interference, and the ability to easily conjugate with drug delivery systems. However, NIR dyes have some drawbacks and limitations, such as low solubility, low stability, and degradation. To overcome these issues, NIR dyes can be encapsulated in appropriate nanocarriers to achieve effective diagnosis, imaging, and therapy monitoring during surgery. Moreover, the vast majority of NIR dyes have photosensitizer features that can effectuate cancer treatment referred to as photodynamic therapy (PDT). In the near future, by combining NIR dyes with appropriate nanocarriers such as liposomes, polymeric micelles, polymeric nanoparticles, dendrimers, quantum dots, carbon nanotubes, or ceramic/silica based nanoparticles, the limitations of NIR dyes can be minimized or even effectively eliminated to form potential effective agents for imaging, therapy, and therapy monitoring of several diseases, particularly cancer.