Gold nanoparticles: an era in bionanotechnology

Introduction: Gold nanoparticles have been efficiently and effectively used for the delivery of biomolecules and genes along with the potential to offer extremely sensitive diagnostics and imaging methods.

Areas covered: This review discusses the historical aspects, synthesis of gold nanoparticles, gold nanoparticles as drug delivery vehicles, photothermal effect of gold nanoparticles and the applications of gold nanoparticles. Gold nanoparticles with their unique optical properties may be useful as biosensors in living cells and has application in the field of drug delivery and photothermal therapy. Depending on the size, shape and degree of aggregation and nature of the protecting organic shells on their surface, gold nanoparticles can appear red, blue and other colors and emit bright resonance light of various wavelengths, which falls under visible region. Because of this property, gold nanoparticles have been extensively used as probes for sensing/imaging a wide range of analysts/targets such as proteins, cells and nucleic acids.

Expert opinion: Gold nanoparticles provide an admirable platform for the delivery of biomolecules and genes.     

Gold nanoparticles in theranostic oncology: current state-of-the-art

Introduction: In recent years, extensive multidisciplinary investigations have been carried out in the area of cancer nanotechnology. Gold nanoparticles (GNPs) have emerged as promising carrier for delivery of various pay-loads into their target. In view of their unique physicochemical and optical properties, GNPs have been exploited for multimodality imaging, tumor targeting, and as transporter of various therapeutics. Additionally, GNPs have been used as photothermal therapeutics against cancer.

Areas covered: This review will focus on recent progress in the field of gold nanomaterials in cancer therapy and diagnosis. Moreover, concern about the toxicity of gold nanomaterials is addressed.

Expert opinion: GNPs present versatile scaffolds for efficient delivery of cancer chemotherapeutics. Tuneable chemistry of the GNPs contributes to their ever increasing use in oncology research. The promises of a functional cancer therapy using GNPs have been extensively demonstrated, although the materials are still in their infancy stage and not surfaced to meet clinical standards.     

Gold nanoparticle conjugates: recent advances toward clinical applications

Introduction: Gold nanoparticles display a unique combination of chemical inertness, surface chemistry and size- and shape-dependent electronic and optical properties, which render them ideal for clinical applications.

Areas covered: The present article describes recent advancements on the application of gold nanoparticles in vaccine development and gene therapy, with augmented efficiencies in cell uptake, specific binding to bioreceptors in cells, protection of conjugated biomolecules and so forth. Additionally, we discuss how the electronic structure of the nanoparticles can be exploited for enhanced radiotherapy and X-ray tomography, while their optical properties can be used for photothermal cancer therapy or light-triggered drug delivery systems for enhanced chemotherapy.

Expert opinion: We analyze certain critical aspects and possible challenges that should be solved in order to use gold nanoparticle conjugates in vaccine research, as well as on the potential combination of properties to improve gene therapy and cancer treatment.     

Phospholipid micelle-based magneto-plasmonic nanoformulation for magnetic field-directed,imaging-guided photo-induced cancer therapy

We present a magnetoplasmonic nanoplatform combining gold nanorods (GNR) and iron-oxide nanoparticles within phospholipid-based polymeric nanomicelles (PGRFe). The gold nanorods exhibit plasmon resonance absorbance at near infrared wavelengths to enable photoacoustic imaging and photothermal therapy, while the Fe₃O₄ nanoparticles enable magnetophoretic control of the nanoformulation. The fabricated nanoformulation can be directed and concentrated by an external magnetic field, which provides enhancement of a photoacoustic signal. Application of an external field also leads to enhanced uptake of the magnetoplasmonic formulation by cancer cells in vitro. Under laser irradiation at the wavelength of the GNR absorption peak, the PGRFe formulation efficiently generates plasmonic nanobubbles within cancer cells, as visualized by confocal microscopy, causing cell destruction. The combined magnetic and plasmonic functionalities of the nanoplatform enable magnetic field-directed, imaging-guided, enhanced photo-induced cancer therapy.From the Clinical EditorIn this study, a nano-formulation of gold nanorods and iron oxide nanoparticles is presented using a phospholipid micelle-based delivery system for magnetic field-directed and imaging-guided photo-induced cancer therapy. The gold nanorods enable photoacoustic imaging and photothermal therapy, while the Fe₃O₄ nanoparticles enable magnetophoretic control of the formulation. This and similar systems could enable more precise and efficient cancer therapy, hopefully in the near future, after additional testing.     

Gold nanoparticles: opportunities and challenges in nanomedicine

Importance of the field: Site-specific drug delivery is an important area of research that is anticipated to increase the efficacy of the drug and reduce potential side effects. Owing to this, substantial work has been done developing non-invasive and targeted tumor treatment with nanoscale metallic particles.

Areas covered in this review: This review focuses on the work done in the last few years developing gold nanoparticles as cancer therapeutics and diagnostic agents. However, there are challenges in using gold nanoparticles as drug delivery systems, such as biodistribution, pharmacokinetics and possible toxicity. Approaches to limit these issues are proposed.

What the reader will gain: Different approaches from several different disciplines are discussed. Potential clinical applications of these engineered nanoparticles are also presented.

Take home message: As a result of their unique size-dependent physicochemical and optical properties, adaptability, subcellular size and biocompatibility, these nanosized carriers offer a suitable means of transporting small molecules as well as biomacromolecules to diseased cells/tissues.     

Surface plasmon resonance-induced photoactivation of gold nanoparticles as mitochondria-targeted therapeutic agents for pancreatic cancer

Background: Noble metal nanoparticles such as gold nanoparticles can strongly absorb light in the visible region by inducing coherent collective oscillation of conduction band electrons in strong resonance with visible frequencies of light. This phenomenon is frequently termed as surface plasmon resonance (SPR).

Objectives: The main objective was to study the effects of laser photoactivated gold nanoparticles (by means of SPR) on human pancreatic cancer cells.

Results: Gold nanoparticles obtained using standard wet chemical methods (with sodium borohydride as a reducing agent) underwent photoexcitation using 2w 808 nm laser and further administered to 1.4E7 pancreatic cancer cell lines. Flow cytometry, transmission electron microscopy, phase contrast microscopy, quantitative proteomics and confocal microscopy combined with immunochemical staining were used to examine the interaction between photo excited gold nanoparticles and pancreatic cancer cells.

Conclusion: The study shows that phonon–phonon interactions following laser photoexcitation of gold nanoparticles exhibit increased intracellular uptake, as well as mitochondrial swelling, closely followed by mitochondrial inner membrane permeabilization and depolarization. This unique data may represent a major step in mitochondria-targeted anticancer therapies using laser-activated gold nanoparticles.     

Metallic nanoparticles: technology overview & drug delivery applications in oncology

Importance of the field: The targeted delivery of therapeutic agents to tumour cells is a challenge because most of the chemotherapeutic agents distribute to the whole body, which results in general toxicity and poor acceptance by patients and sometimes discontinuation of the treatment. Metallic nanoparticles have been used for a huge number of applications in various areas of medical treatment. Metallic nanoparticles are emerging as new carrier and contrast agents in cancer treatment. These metallic nanoparticles have been used for imaging of tumour cells by means of active and passive targeting. Recent advances have opened the way to site-specific targeting and drug delivery by these nanoparticles.

Areas covered in this review: This review summarizes the mechanisms of passive and active targeted drug delivery by metallic nanoparticles and their potential use in cancer theranostics.

What the reader will gain: The reader will gain information on the development of tumour cells, advantages of modern methods of cancer treatment over the traditional method, targeted delivery of anticancer agents using nanoparticles, influence of nanotechnology on the quality and expectancy of life, and challenges, implications and future prospects of metallic nanoparticles as probes in cancer treatment.

Take home message: The development of metallic nanoparticles is rapid and multidirectional, and the improved practical potential of metallic nanoparticle highlights their potency as new tools for future cancer therapeutics modalities.     

Tunable gold nanostar synthesis with surfactant-free system

Gold nanoparticle is an important photothermal conversion material in photothermal imaging and photothermal therapy research. There are diverse gold nanoparticles, including gold nanospheres, gold nanorods, gold nanocages, gold nanoshells and gold nanostars. Among them, gold nanostar (AuNS) possesses more excellent prospective imaging contrast agent for cancer diagnosis than other shapes of gold nanoparticles because of its larger photon interception area and cross section as well asscattering characteristics. The properties of AuNS are susceptible to synthetic methods and conditions. In this study, we presented surfactant-free methods to synthesize AuNS, discussed the relationship of AuNS characterization with the synthetic conditions and tested its photothermal effect. The results indicated that length and number of branches in AuNSs were the main factor for absorption wavelength in photothermal conversion, and the AuNSs could be more precisely controlled by changing the synthesis conditions.     

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.     

Enhancing the efficiency of bortezomib conjugated to pegylated gold nanoparticles: an in vitro study on human pancreatic cancer cells and adenocarcinoma human lung alveolar basal epithelial cells

ABSTRACT

Objectives: Gold nanoparticles have become promising vectors for cancer diagnosis and treatment. The present study investigates the effect of bortezomib (BTZ), a proteasome inhibitor, conjugated with pegylated gold nanoparticles (PEGAuNPs) in pancreatic and lung cancer cells.

Methods: Synthesized gold nanoparticles (PEGAuNPs) were conjugated with bortezomib antitumor drug. We investigated the cytotoxicity induced by BTZ conjugated with functionalized gold nanoparticles in vitro, in the human pancreatic (S2-013) and lung (A549) cancer cell lines.

Results: We found an efficient of conjugation of BTZ with PEGAuNPs. In vitro assays showed that after 72 h’ incubation with PEGAuNPs-BTZ cancer cells revealed alterations in morphology; also for S2-013 and A549 cancer cells, the IC₅₀ value of free BTZ is respectively 1.5 and 4.3 times higher than the IC₅₀ value of PEGAuNPs-BTZ. Furthermore, for TERT-HPNE, the IC₅₀ value is around 63 times lower for free BTZ than the conjugated nanovehicle. Cell growth inhibition results showed a remarkable enhancement in the effect of BTZ when conjugated with AuNPs.

Conclusions: Our findings showed that conjugation with PEGAuNPs enhance the BTZ growth-inhibition effect on human cancer cells (S2-013 and A549) and decreases its toxicity against normal cells (TERT-HPNE).     

Zinc oxide nanoparticles for selective destruction of tumor cells and potential for drug delivery applications

Importance of the field: Metal oxide nanoparticles, including zinc oxide, are versatile platforms for biomedical applications and therapeutic intervention. There is an urgent need to develop new classes of anticancer agents, and recent studies demonstrate that ZnO nanomaterials hold considerable promise.

Areas covered in this review: This review analyzes the biomedical applications of metal oxide and ZnO nanomaterials under development at the experimental, preclinical and clinical levels. A discussion regarding the advantages, approaches and limitations surrounding the use of metal oxide nanoparticles for cancer applications and drug delivery is presented. The scope of this article is focused on ZnO, and other metal oxide nanomaterial systems, and their proposed mechanisms of cytotoxic action, as well as current approaches to improve their targeting and cytotoxicity against cancer cells.

What the reader will gain: This review aims to give an overview of ZnO nanomaterials in biomedical applications.

Take home message: Through a better understanding of the mechanisms of action and cellular consequences resulting from nanoparticles interactions with cells, the inherent toxicity and selectivity of ZnO nanoparticles against cancer may be improved further to make them attractive new anticancer agents.     

Cationic nanoparticles for cancer therapy

Importance of the field: The lack of selective delivery of therapeutic molecules to cancer cells remains a problem in cancer therapy. As a result of this non-selectivity, cytotoxic agents are delivered to both healthy and cancerous cells, resulting in severe side effects for the patient, eventually causing termination of therapy or ineffective therapy resulting in progression or recurrence of the disease. In this context, cationic polymers with net positive surface charge emerge as a promising option owing to their very strong cellular interaction properties and good cellular uptake.

Areas covered in this review: In this review, the structure, characteristics and preparation techniques for cationic nanoparticulate drug delivery systems are discussed in the light of cytotoxicity associated with cationic polymers and strong complement activation properties of cationic carrier systems on injection. In vivo behavior and biodistribution of cationic nanoparticles are also reviewed for a better understanding of biological interaction of cationic nanoparticles.

What the reader will gain: This review will give an insight to the properties of cationic polymers, including their advantages and drawbacks and drug/gene delivery systems based on cationic polymers intended for cancer therapy.

Take home message: Cationic polymer-based nanoparticles emerge as a promising group of nanosize carrier systems to the tumor cell level with a wide range of modification and application possibilities.     

Electrostatic surface modifications to improve gene delivery

Importance of the field: Gene therapy has the potential to treat a wide variety of diseases, including genetic diseases and cancer.

Areas covered in this review: This review introduces biomaterials used for gene delivery and then focuses on the use of electrostatic surface modifications to improve gene delivery materials. These modifications have been used to stabilize therapeutics in vivo, add cell-specific targeting ligands, and promote controlled release. Coatings of nanoparticles and microparticles as well as non-particulate surface coatings are covered in this review. Electrostatic principles are crucial for the development of multilayer delivery structures fabricated by the layer-by-layer method.

What the reader will gain: The reader will gain knowledge about the composition of biomaterials used for surface modifications and how these coatings and multilayers can be utilized to improve spatial control and efficiency of delivery. Examples are shown for the delivery of nucleic acids, including DNA and siRNA, to in vitro and in vivo systems.

Take home message: The versatile and powerful approach of electrostatic coatings and multilayers will lead to the development of enhanced gene therapies.     

Gold nanostars-diagnosis,bioimaging and biomedical applications

Abstract

Gold Nanostars (GNS) have attracted tremendous attention toward themselves owing to their multi-branched structure and unique properties. These state of the art metallic nanoparticles possess intrinsic features like remarkable optical properties and exceptional physiochemical activities. These star-shaped gold nanoparticles can predominantly be utilized in biosensing, photothermal therapy, imaging, surface-enhanced Raman spectroscopy and target drug delivery applications due to their low toxicity and extraordinary optical features. In the current review, recent approaches in the matter of GNS in case of diagnosis, bioimaging and biomedical applications were summarized and reported. In this regard, first an overview about the structure and general properties of GNS were reported and thence detailed information regarding the diagnostic, bioimaging, photothermal therapy, and drug delivery applications of such novel nanomaterials were presented in detail. Summarized information clearly highlighting the superior capability of GNS as potential multi-functional materials for biomedical applications.     

Chemotherapy regimens and treatment protocols for laryngeal cancer

Importance of the field: Laryngeal cancer has been the model of curative-intent organ-preserving therapies in clinical oncology. Although the optimal care of patients with laryngeal cancer is truly multidisciplinary, with progressive advances in surgical, radiation, and medical oncology, the development of effective systemic therapies has been a major component of the therapeutic arsenal against laryngeal cancer.

Areas covered in this review: This review will discuss the rapidly evolving roles of chemotherapy in the management of locally advanced and metastatic laryngeal cancer.

What the reader will gain: The reader will gain a historical perspective on this evolution in treatment and will appreciate current treatment challenges and promising future directions in optimizing therapeutic efficacy in functional larynx preservation and in patient survival.

Take home message: The treatment of most patients with laryngeal cancer with systemic therapy represents an opportunity to positively impact functional outcomes with an anatomically and functionally preserved larynx. Future challenges include identification of novel therapies and optimizing therapy protocols for individualized patient care.     

Emerging MEK inhibitors

Importance of the field: The Ras/Raf/MEK/ERK pathway is often activated by genetic alterations in upstream signaling molecules. Integral components of this pathway such as Ras and B-Raf are also activated by mutation. The Ras/Raf/MEK/ERK pathway has profound effects on proliferative, apoptotic and differentiation pathways. This pathway can often be effectively silenced by MEK inhibitors.

Areas covered by this review: This review will discuss targeting of MEK which could lead to novel methods to control abnormal proliferation which arises in cancer and other proliferative diseases. This review will cover the scientific literature from 1980 to present and is a follow on from a review which focused on Emerging Raf Inhibitors published in this same review series.

What the reader will gain: By reading this review the reader will understand the important roles that genetics play in the response of patients to MEK inhibitors, the potential of combining MEK inhibitors with other types of therapy, the prevention of cellular aging and the development of cancer stem cells.

Take home message: Targeting MEK has been shown to be effective in suppressing many important pathways involved in cell growth and the prevention of apoptosis. MEK inhibitors have many potential therapeutic uses in the suppression of cancer, proliferative diseases and aging.     

Anastrozole

Importance of the field: Anastrozole is a third-generation aromatase inhibitor used in the adjuvant setting for the treatment of hormone receptor-positive breast cancer. Several adjuvant randomized trials have reported greater efficacy for anastrozole when compared to tamoxifen.

Areas covered in this review: This review discusses the mechanism of action of anastrozole; pharmacokinetic and pharmacodynamic characteristics; results of randomized controlled trials of anastrozole compared to tamoxifen in the adjuvant treatment of postmenopausal women with hormone receptor-positive breast cancer and the safety profile of anastrozole compared to tamoxifen.

What the reader will gain: The reader will gain an understanding of the basic pharmacology of anastrozole, efficacy data from clinical trials comparing anastrozole to tamoxifen, safety profile of anastrozole and ongoing areas of research.

Take home message: The adverse effects of anastrozole.     

Lapatinib for breast cancer: a review of the current literature

Importance of the field: The identification of HER-2 expression as a predictive and prognostic marker revolutionized breast cancer. Trastuzumab, a humanized mAb, improves survival in both early and advanced HER-2 overexpressing breast cancer. However, many cancers either do not respond or develop resistance to this agent. Lapatinib is an oral tyrosine kinase inhibitor which has both HER-1 and -2 activities and has been licensed for use in recurrent breast cancer that overexpresses HER-2. Studies of lapatinib in early breast cancer are ongoing.

Areas covered in this review: A PubMed search was conducted using ‘lapatinib’ and ‘breast cancer’ as the key words. All published works up to July 2010 were reviewed. A manual review of abstracts presented at the ASCO Annual meeting and the San Antonio Breast Cancer Symposium was conducted for the last 2 years. In this review, we summarize the current knowledge of lapatinib and pose questions which need to be addressed as we further expand our knowledge of the HER-2 subtypes of breast cancer.

What the reader will gain: The reader will gain an up-to-date and comprehensive review of the current literature as it pertains to the safety and efficacy of lapatinib in the treatment of breast cancer.

Take home message: Lapatinib has provided an alternative for the treatment of advanced HER-2 overexpressing breast cancer and is currently being assessed in early disease.     

Targeting miR-21 in glioma: a small RNA with big potential

Importance of the field: Glioma therapies have produced relatively small improvements over the past decade, highlighting an important need to identify novel ways to target this disease. Targeted therapies against single activated protein kinases have proven effective in some cancers including gastrointestinal stromal cancer and colon cancer, but not yet in gliomas where multiple pathways and targets may be involved. MicroRNAs are emerging as key regulators of multiple pathways involved in cancer development and progression and may become the next targeted therapies in glioma.

Areas covered in this review: This review covers the basics of microRNA biology and specifically focuses on the roles of miR-21 in glioma and its potential as target for glioma therapy.

What the reader will gain: This review will provide the reader with an in depth understanding of how miR-21 functions in glioma. We also review the current state of studies designed to specifically target miR-21 as a potential future therapeutic.

Take home message: Identifying novel targets for the treatment of glioma is critical for advancing the current state of the field. MicroRNAs provide a novel target; and in glioma, targeting miR-21 may have broad consequences for the tumor that make it an attractive potential therapeutic.