Paper-based immunosensor with signal amplification by enzyme-labeled anti-p16INK4a multifunctionalized gold nanoparticles for cervical cancer screening

The aim of this study was to develop a paper-based immunosensor for cervical cancer screening, with signal amplification by multifunctionalized gold nanoparticles (AuNPs). The AuNPs were functionalized with a highly specific antibody to the p16^INK4a cancer biomarker. The signal was amplified using a combination of the peroxidase activity of horseradish peroxidase (HRP) enzyme-antibody conjugate and the peroxidase-like activity of the AuNPs. The immune complex of p16^INK4a protein and multifunctionalized AuNPs was deposited on the nitrocellulose membrane, and a positive result was generated by catalytic oxidation of peroxidase enzyme substrate 3,3’,5,5’-Tetramethylbenzidine (TMB). The entire reaction occurred on the membrane within 30 min. Evaluation in clinical samples revealed 85.2% accuracy with a kappa coefficient of 0.69. This proof of concept study demonstrates the successful development of a highly accurate, paper-based immunosensor that is easy to interpret using the naked eye and that is suitable for cervical cancer screening in low-resource settings.     

CT imaging of myocardial scars with collagen-targeting gold nanoparticles

In the setting of myocardial ischemia, recovery of myocardial function by revascularization procedures depends on the extent of coronary disease and myocardial scar burden. Currently, computed tomographic (CT) imaging offers superior evaluation of coronary lesions but lacks the capability to measure the transmural extent of myocardial scar. Our work focuses on determining if collagen-targeting gold nanoparticles (AuNPs) can effectively target myocardial scar and provide adequate contrast for CT imaging. AuNPs were coated with a collagen-homing peptide, collagen adhesin (CNA35). Myocardial scar was created in mice by occlusion/reperfusion of the left anterior descending coronary artery. Thirty days later, un-gated CT imaging was performed. Over 6 h, CNA35-AuNPs provided uniform and prolonged opacification of the vascular structures (100-130 HU). In mice with larger scar burden, focal contrast enhancement was detected in the myocardium, which was not apparent within that of control mice. Histological staining confirmed myocardial scar formation and accumulation of AuNPs.From the Clinical EditorThis team of investigators presents a collagen-targeting gold nanoparticle-based approach that enables the imaging of myocardial scars via CT scans in a rodent model. This information would enable clinicians to judge the recovery potential of myocardium more accurately than the current CT-scan based approaches.     

Fabrication of gold nanoparticles for targeted therapy in pancreatic cancer

The targeted delivery of a drug should result in enhanced therapeutic efficacy with low to minimal side effects. This is a widely accepted concept, but limited in application due to lack of available technologies and process of validation. Biomedical nanotechnology can play an important role in this respect. Biomedical nanotechnology is a burgeoning field with myriads of opportunities and possibilities for advancing medical science and disease treatment. Cancer nanotechnology (1–100 nm size range) is expected to change the very foundations of cancer treatment, diagnosis and detection. Nanomaterials, especially gold nanoparticles (AuNPs) have unique physico-chemical properties, such as ultra small size, large surface area to mass ratio, and high surface reactivity, presence of surface plasmon resonance (SPR) bands, biocompatibility and ease of surface functionalization. In this review, we will discuss how the unique physico-chemical properties of gold nanoparticles may be utilized for targeted drug delivery in pancreatic cancer leading to increased efficacy of traditional chemotherapeutics.     

Multifunctional magnetic nanoparticles for targeted imaging and therapy

Magnetic nanoparticles have become important tools for the imaging of prevalent diseases, such as cancer, atherosclerosis, diabetes, and others. While first generation nanoparticles were fairly nonspecific, newer generations have been targeted to specific cell types and molecular targets via affinity ligands. Commonly, these ligands emerge from phage or small molecule screens, or are based on antibodies or aptamers. Secondary reporters and combined therapeutic molecules have further opened potential clinical applications of these materials. This review summarizes some of the recent biomedical applications of these newer magnetic nanomaterials.     

Towards the use of nanoparticles in cancer therapy and imaging

Nanosystems have unique physical and biological properties. Various systems have been designed for medical use and offer promising ways of delivering drugs at high concentrations at sites of interest, e.g., cancer lesions, while reducing systemic side effects. Nanotechnology has also opened ways for the development of contrast agents and radiopharmaceuticals for specific targeting, which is presently changing research strategies in the field of magnetic resonance imaging, ultrasound imaging and nuclear medicine applications. This article aims to overview how "nanomedicine" is presently influencing drug design for diagnostic and therapeutic purposes.     

Multifunctional nanoparticles for imaging,delivery and targeting in cancer therapy

The application of nanoparticles for the delivery and targeting of pharmaceutical, therapeutic and diagnostic agents in cancer therapy has received significant attention in recent years. Nanoparticles may be constructed from a wide range of materials and used to encapsulate or solubilize chemotherapeutic agents for improved delivery in vivo or to provide unique optical, magnetic and electrical properties for imaging and therapy. Several functional nanoparticles have already been demonstrated, including some clinically approved liposome drug formulations and metallic imaging agents. The next generation of nanoparticle-based research is directed at the consolidation of functions into strategically engineered multifunctional systems, which may ultimately facilitate the realization of individual therapy. These multiplexed nanoparticles may be capable of identifying malignant cells by means of molecular detection, visualizing their location in the body by providing enhanced contrast in medical imaging techniques, killing diseased cells with minimal side effects through selective drug targeting, and monitoring treatment in real time. This article highlights recent progress in the design and engineering of multifunctional systems, as well as discusses the development of a new, scalable and economic method for the modular preparation of multiplex nanoparticles where functional properties can be precisely and simply tailored.     

Targeted imaging and therapy of brain cancer using theranostic nanoparticles

The past decade has seen momentous development in brain cancer research in terms of novel imaging-assisted surgeries, molecularly targeted drug-based treatment regimens or adjuvant therapies and in our understanding of molecular footprints of initiation and progression of malignancy. However, mortality due to brain cancer has essentially remained unchanged in the last three decades. Thus, paradigm-changing diagnostic and therapeutic reagents are urgently needed. Nanotheranostic platforms are powerful tools for imaging and treatment of cancer. Multifunctionality of these nanovehicles offers a number of advantages over conventional agents. These include targeting to a diseased site thereby minimizing systemic toxicity, the ability to solubilize hydrophobic or labile drugs leading to improved pharmacokinetics and their potential to image, treat and predict therapeutic response. In this article, we will discuss the application of newer theranostic nanoparticles in targeted brain cancer imaging and treatment.     

Enhancement of radiation effects by gold nanoparticles for superficial radiation therapy

Iodinated contrast agents, which are routinely used to improve contrast in x-ray diagnostic radiography, have been successfully proven to enhance radiation effects in kilovoltage x-ray radiation therapy beams. The studies determined the influence of iodine on the level of radiation biotoxicity to cells as an indicator of the radiation dose enhancement. The use of other high-atomic-number materials such as gold nanoparticles (AuNPs) may also provide advantages in terms of radiation dose enhancement. In this work AuNPs have been used for the enhancement of radiation effects on bovine aortic endothelial cells of superficial x-ray radiation therapy and megavoltage electron radiation therapy beams. Results reveal an increase of cell damage with increasing concentration of AuNPs. At 1 mM concentration of AuNPs, enhancement of radiation peaked at 25 times for a kilovoltage x-ray beam. AuNPs showed similar effects on electron beams but to a lesser extent. This study showed that AuNPs can be used to enhance the effect of radiation doses from kilovoltage x-ray radiation therapy and megavoltage electron radiation therapy beams. In the prevailing clinical circumstances, wherein radiation therapy dose is constrained by normal tissue tolerance, this enhancement could in the future be used to improve local control in superficial x-ray treatments, megavoltage electron beam radiation therapy, microbeam radiation therapy, and intraoperative irradiation using kilovoltage x-rays or megavoltage electron beams. Moreover, the value of this work also stems from the fact that the damage to the endothelial cells lining the highly vasculature structure of tumors deprives tumors of their oxygen and nutrients supply and enhances the efficiency of radiation therapy treatment, where it has been proven that more of the AuNPs injected into animals ends up into the blood than in the tumor.     

Targeted near-IR hybrid magnetic nanoparticles for in vivo cancer therapy and imaging

We report the use of immuno-targeted gold–iron oxide hybrid nanoparticles for laser-assisted therapy and for MRI-based imaging as demonstrated in xenograft colorectal cancer tumor model. Immuno-targeted gold–iron oxide nanoparticles selectively accumulate in SW1222 xenograft tumors as compared to the accumulation in non-antigen-expressing tumor xenografts. Effective photothermal treatment using near-IR laser irradiation (808 nm, 5 W cm^? 2) application is shown where > 65% of the antigen-expressing tumor cells presented corrupt extracellular matrix and cytoplasmic acidophilia suggesting effectiveness of nanoparticle-assisted thermal therapy. Cell killing was confirmed by hematoxylin and eosin (H&E) histological staining where scar-like structure containing collagen bundles was observed in the treatment group. Further, systemically injected HNPs were shown to be effective T₂ magnetic resonance (MR) imaging contrast agents, localized and detected at the antigen-expressing xenograft tumors. These findings suggest that the new class of bio-conjugated HNPs exhibits great potential for dual-therapy and diagnostics (theranostics) applications.From the Clinical EditorThis team reports the successful use of immuno-targeted gold-iron oxide hybrid nanoparticles for both laser-assisted therapy and MRI-based imaging in a xenograft colorectal cancer tumor model, demonstrating strong potentials for dual applications in cancer diagnosis and therapy.     

Targeted 64Cu‐labeled gold nanoparticles for dual imaging with positron emission tomography and optical imaging

Gold nanoparticles (AuNPs) have been used for many years in cancer treatment mainly for brachytherapy, but in the last 15 years, the focus has shifted to the development of ultrasmall target‐specific AuNPs with homogeneous size and, ultimately, tailored shapes for use in various imaging modalities such as computed tomography (CT), Raman, or photoacoustic imaging. Here, we report on the development of tumor‐specific AuNPs as diagnostic tools intended for the dual detection of prostate cancer via optical imaging (OI) and positron emission tomography (PET). The AuNPs were decorated with a near‐infrared dye and NODAGA chelator for complexation with radiometals. Radiolabeling with ⁶⁴Cu was performed either indirect by complexation with NODAGA‐AuNPs or by direct reduction of [⁶⁴Cu]Cu(0) onto the surface of the AuNPs. Both methods yielded stable ⁶⁴Cu‐AuNPs with radiochemical yield more than 95% confirmed by HPLC. ⁶⁴Cu‐AuNPs were evaluated in a dual‐imaging setting in vitro and in vivo and exhibited favorable diagnostic properties concerning detection, biodistribution, and clearance. Furthermore, the first therapeutic properties of the ⁶⁴Cu‐AuNPs were evaluated in vitro concerning acute and long‐term toxicity, indicating that these ⁶⁴Cu‐AuNPs could be used in therapeutic concepts in the future.     

Encapsulating gold nanomaterials into size-controlled human serum albumin nanoparticles for cancer therapy platforms

Abstract

Progress has been made in using human serum albumin nanoparticles (HSAPs) as promising colloidal carrier systems for early detection and targeted treatment of cancer and other diseases. Despite this success, there is a current lack of multi-functional HSAP hybrids that offer combinational therapies. The size of the HSAPs has crucial importance on drug loading and in vivo performance and has previously been controlled via manipulation of pH and cross-linking parameters. Gold nanomaterials have also gained attention for medicinal use due to their ability to absorb near-infrared light, thus offering photothermal capabilities. In this study, the desolvation and cross-linking approach was employed to encapsulate gold nanorods, nanoparticles, and nanoshells into HSAPs. Incorporation of gold nanomaterials caused some changes in HSAP sizes, but the general size trends remained. This encasement strategy facilitated size-controlled HSAPs, in the range of 100–300?nm, loaded with gold nanostructures; providing composite particles which incorporate photothermally active components.     

SPECT/CT imaging of chemotherapy-induced tumor apoptosis using 99mTc-labeled dendrimer-entrapped gold nanoparticles

Non-invasive imaging of apoptosis in tumors induced by chemotherapy is of great value in the evaluation of therapeutic efficiency. In this study, we report the synthesis, characterization, and utilization of radionuclide technetium-99m (^99mTc)-labeled dendrimer-entrapped gold nanoparticles (Au DENPs) for targeted SPECT/CT imaging of chemotherapy-induced tumor apoptosis. Generation five poly(amidoamine) (PAMAM) dendrimers (G5.NH₂) were sequentially conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), polyethylene glycol (PEG) modified duramycin, PEG monomethyl ether, and fluorescein isothiocyanate (FI) to form the multifunctional dendrimers, which were then utilized as templates to entrap gold nanoparticles. Followed by acetylation of the remaining dendrimer surface amines and radiolabeling of ^99mTc, the SPECT/CT dual mode nanoprobe of tumor apoptosis was constructed. The developed multifunctional Au DENPs before and after ^99mTc radiolabeling were well characterized. The results demonstrate that the multifunctional Au DENPs display favorable colloidal stability under different conditions, own good cytocompatibility in the given concentration range, and can be effectively labeled by ^99mTc with high radiochemical stability. Furthermore, the multifunctional nanoprobe enables the targeted SPECT/CT imaging of apoptotic cancer cells in vitro and tumor apoptosis after doxorubicin (DOX) treatment in the established subcutaneous tumor model in vivo. The designed duramycin-functionalized Au DENPs might have the potential to be employed as a nanoplatform for the detection of apoptosis and early tumor response to chemotherapy.     

Radiotherapy enhancement with gold nanoparticles

Gold is an excellent absorber of X-rays. If tumours could be loaded with gold, this would lead to a higher dose to the cancerous tissue compared with the dose received by normal tissue during a radiotherapy treatment. Calculations indicate that this dose enhancement can be significant, even 200% or greater. In this paper, the physical and biological parameters affecting this enhancement are discussed. Gold nanoparticles have shown therapeutic efficacy in animal trials and these results are reviewed. Some 86% long-term (>1 year) cures of EMT-6 mouse mammary subcutaneous tumours was achieved with an intravenous injection of gold nanoparticles before irradiation with 250-kVp photons, whereas only 20% were cured with radiation alone. The clinical potential of this approach is also discussed.     

Anti-glycation activity of gold nanoparticles

Anti-glycation activity of gold nanoparticles (GNPs) has been reported for the first time. Nonenzymatic glycation of alpha-crystallin leads to formation of cataract, or opaque aggregate of proteins. In this article we report prevention of glycation of alpha-crystallin by conjugation with GNPs. Formation of advanced glycosylic end products is prevented even if a strong glycating agent such as fructose is used. In addition, the nanoconjugation can provide some important information on the structural distribution of this dynamic chaperone protein. Because GNPs are biocompatible, their reported anti-glycation activity may have ophthalmological implications.     

Recent development of silica nanoparticles as delivery vectors for cancer imaging and therapy

In spite of significant advances in early detection and combined treatments, a number of cancers are often diagnosed at advanced stages and thereby carry a poor prognosis. Developing novel prognostic biomarkers and targeted therapies may offer alternatives for cancer diagnosis and treatment. Recent rapid development of nanomaterials, such as silica based nanoparticles (SiNPs), can just render such a promise. In this article, we attempt to summarize the recent progress of SiNPs in tumor research as a novel delivery vector. SiNP-assisted imaging techniques are used in cancer diagnosis both in vitro and in vivo. Meanwhile, SiNP-mediated drug delivery can efficiently treat tumor by carrying chemotherapeutic agents, photosensitizers, photothermal agents, siRNA, and gene therapeutic agents. Finally, SiNPs that contain at least two different functional agents may be more powerful for both tumor imaging and therapy.From the Clinical EditorThis paper summarizes recent progress on the field of silica nanoparticles research as novel delivery vectors for cancer-specific imaging as well as drug delivery of chemotherapeutics, photosensitizers, photothermal agents, siRNA, and gene therapy agents.     

Magnetic nanoparticles: an emerging technology for malignant brain tumor imaging and therapy

Magnetic nanoparticles (MNPs) represent a promising nanomaterial for the targeted therapy and imaging of malignant brain tumors. Conjugation of peptides or antibodies to the surface of MNPs allows direct targeting of the tumor cell surface and potential disruption of active signaling pathways present in tumor cells. Delivery of nanoparticles to malignant brain tumors represents a formidable challenge due to the presence of the blood-brain barrier and infiltrating cancer cells in the normal brain. Newer strategies permit better delivery of MNPs systemically and by direct convection-enhanced delivery to the brain. Completion of a human clinical trial involving direct injection of MNPs into recurrent malignant brain tumors for thermotherapy has established their feasibility, safety and efficacy in patients. Future translational studies are in progress to understand the promising impact of MNPs in the treatment of malignant brain tumors.     

载阿霉素金纳米粒的制备和细胞毒性研究

目的 构建载阿霉素（DOX）的甲氧基聚乙二醇（mPEG）修饰的金纳米粒AuNPs-mPEG@DOX，以降低DOX的毒副作用。方法 制备AuNPs-mPEG@DOX，通过粒径、电位和紫外可见光吸收光谱（UV-Vis）进行表征。考察连接巯基的DOX（HS-DOX）投药浓度对AuNPs-mPEG@DOX吸附率和载药量的影响。建立未吸附HS-DOX含量测定的高效液相色谱法（HPLC），对专属性、线性、精密度、稳定性和加样回收率进行考察。采用CCK-8法检测AuNPs-mPEG@DOX对MCF-10A和MCF-7细胞的毒性作用。结果 成功制备了AuNPs-mPEG@DOX，粒径为（46.12±0.49） nm，电位为（18.60±1.51） mV，最大吸收波长为530 nm。建立了可用于检测AuNPs-mPEG@DOX未吸附HS-DOX含量的HPLC方法，测定最佳投药浓度11.18 μg/ml，HS-DOX条件下的吸附率为（9.21±2.88）%，载药量为（2.01±0.62）%。细胞毒性实验表明AuNPs-mPEG@DOX可明显降低DOX对正常乳腺细胞的毒副作用；DOX在≥4.75 μmol/L时，AuNPs-mPEG@DOX与游离DOX对乳腺肿瘤细胞的细胞毒性作用一致。结论 AuNPs-mPEG@DOX可有效降低DOX的毒副作用，为后续AuNPs连接药物降低其毒副作用的研究提供参考。     

Labeling and tracking cells with gold nanoparticles

Gold nanoparticles (AuNPs) have garnered much attention as contrast agents for computerized tomography (CT) because of their facile synthesis and surface functionalization, in addition to their significant X-ray attenuation and minimal cytotoxicity. Cell labeling using AuNPs and tracking of the labeled cells using CT has become a time-efficient and cost-effective method. Actively targeted AuNPs can enhance CT contrast and sensitivity, and further reduce the radiation dosage needed during CT imaging. In this review, we summarize the state-of-the-art use of AuNPs in CT for cell tracking, including the precautionary steps necessary for their use and the difficulty in translating the process into clinical use.     

Review on gold nanoparticles and their applications

Gold nanoparticles are widely used in many fields as preferred materials for their unique optical and physical properties, such as surface plasmon oscillations for labeling, imaging, and sensing. Recently, many advancements were made in biomedical applications with better biocompatibility in disease diagnosis and therapeutics. Au-NPs could be prepared and conjugated with many functionalizing agents, such as polymers, surfactants, ligands, dendrimers, drugs, DNA, RNA, proteins, peptides and oligonucleotides. This review addressed the use of gold nanoparticles and the surface functionalization with a wide range of molecules, expanding and improving gold nanoparticles in targeting drugs for photothermal therapy with reduced cytotoxic effcts in various cancers, gene therapy and many other diseases. Overall, Au-NPs would be a promising vehicle for drug delivery and therapies.