Gold Nanostructures as a Platform for Combinational Therapy in Future Cancer Therapeutics
04 Mar 2011-Cancers (Multidisciplinary Digital Publishing Institute (MDPI))-Vol. 3, Iss: 1, pp 1081-1110
TL;DR: A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research.
Abstract: The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of spherical gold NPs (GNPs), gold nanorods (GNRs), gold nanoshells (GNSs) and gold nanocages (GNCs) in cancer therapeutics. In treating cancer, radiation therapy and chemotherapy remain the most widely used treatment options and recent developments in cancer research show that the incorporation of gold nanostructures into these protocols has enhanced tumor cell killing. These nanostructures further provide strategies for better loading, targeting, and controlling the release of drugs to minimize the side effects of highly toxic anticancer drugs used in chemotherapy and photodynamic therapy. In addition, the heat generation capability of gold nanostructures upon exposure to UV or near infrared light is being used to damage tumor cells locally in photothermal therapy. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research.
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TL;DR: The known mechanisms for Au NP biosynthesis in viable fungi and fungal protein extracts are described and the most suitable bioreactors for industrial AuNP biosynthesis are discussed.
Abstract: Gold nanoparticles (AuNPs) are a widespread research tool because of their oxidation resistance, biocompatibility and stability. Chemical methods for AuNP synthesis often produce toxic residues that raise environmental concern. On the other hand, the biological synthesis of AuNPs in viable microorganisms and their cell-free extracts is an environmentally friendly and low-cost process. In general, fungi tolerate higher metal concentrations than bacteria and secrete abundant extracellular redox proteins to reduce soluble metal ions to their insoluble form and eventually to nanocrystals. Fungi harbour untapped biological diversity and may provide novel metal reductases for metal detoxification and bioreduction. A thorough understanding of the biosynthetic mechanism of AuNPs in fungi is needed to reduce the time of biosynthesis and to scale up the AuNP production process. In this review, we describe the known mechanisms for AuNP biosynthesis in viable fungi and fungal protein extracts and discuss the most suitable bioreactors for industrial AuNP biosynthesis.
253 citations
TL;DR: This is the first paper that highlights the novel and future therapeutic perspectives for the treatment of skin malignancies, new therapeutic agents and promising technological approaches, from nanotechnology to immunotherapy.
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TL;DR: This review focuses on the biogenic synthesis of metal nanoparticles by fungi to explore the chemistry of their formation extracellularly and intracellularly.
Abstract: Fungi secrete enzymes and proteins as reducing agents which can be used for the synthesis of metal nanoparticles from metal salts. Large-scale production of nanoparticles from diverse fungal strains has great potential since they can be grown even in vitro. In recent years, various approaches have been made to maximize the yield of nanoparticles of varying shape, size, and stability. They have been characterized by thermogravimetric analysis, X-ray diffractometry, SEM/TEM, zeta potential measurements, UV-vis, and Fourier transform infrared (FTIR) spectroscopy. In this review, we focus on the biogenic synthesis of metal nanoparticles by fungi to explore the chemistry of their formation extracellularly and intracellularly. Emphasis has been given to the potential of metal nanoparticles as an antimicrobial agent to inhibit the growth of pathogenic fungi, and on other potential applications.
238 citations
TL;DR: The general strategies of nanomaterial-mediated tumor radiosensitization are comprehensively summarized, particularly aiming at introducing the emerging radiosensitive methods.
Abstract: Nano-radiosensitization has been a hot concept for the past ten years, and the nanomaterial-mediated tumor radiosensitization method is mainly focused on increasing intracellular radiation deposition by high atomic number (high Z) nanomaterials, particularly gold (Au)-mediated radiation enhancement. Recently, various new nanomaterial-mediated radiosensitive approaches have been successively reported, such as catalyzing reactive oxygen species (ROS) generation, consuming intracellular reduced glutathione (GSH), overcoming tumor hypoxia, and various synergistic radiotherapy ways. These strategies may open a new avenue for enhancing the radiotherapeutic effect and avoiding its side effects. Nevertheless, reviews systematically summarizing these newly emerging methods and their radiosensitive mechanisms are still rare. Therefore, the general strategies of nanomaterial-mediated tumor radiosensitization are comprehensively summarized, particularly aiming at introducing the emerging radiosensitive methods. The strategies are divided into three general parts. First, methods on account of the intrinsic radiosensitive properties of nanoradiosensitizers for radiosensitization are highlighted. Then, newly developed synergistic strategies based on multifunctional nanomaterials for enhancing radiotherapy efficacy are emphasized. Third, nanomaterial-mediated radioprotection approaches for increasing the radiotherapeutic ratio are discussed. Importantly, the clinical translation of nanomaterial-mediated tumor radiosensitization is also covered. Finally, further challenges and outlooks in this field are discussed.
205 citations
TL;DR: Some general design considerations of advanced theranostic materials and challenges of their use, from both diagnostic and therapeutic perspectives, are discussed.
Abstract: Nanoscale materials have been explored extensively as agents for therapeutic and diagnostic (i.e. theranostic) applications. Research efforts have shifted from exploring new materials in vitro to designing materials that function in more relevant animal disease models, thereby increasing potential for clinical translation. Current interests include non-invasive imaging of diseases, biomarkers and targeted delivery of therapeutic drugs. Here, we discuss some general design considerations of advanced theranostic materials and challenges of their use, from both diagnostic and therapeutic perspectives. Common classes of nanoscale biomaterials, including magnetic nanoparticles, quantum dots, upconversion nanoparticles, mesoporous silica nanoparticles, carbon-based nanoparticles and organic dye-based nanoparticles, have demonstrated potential for both diagnosis and therapy. Variations such as size control and surface modifications can modulate biocompatibility and interactions with target tissues. The needs for improved disease detection and enhanced chemotherapeutic treatments, together with realistic considerations for clinically translatable nanomaterials will be key driving factors for theranostic agent research in the near future.
186 citations
References
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TL;DR: The arsenal of nanocarriers and molecules available for selective tumour targeting, and the challenges in cancer treatment are detailed and emphasized.
Abstract: Nanotechnology has the potential to revolutionize cancer diagnosis and therapy. Advances in protein engineering and materials science have contributed to novel nanoscale targeting approaches that may bring new hope to cancer patients. Several therapeutic nanocarriers have been approved for clinical use. However, to date, there are only a few clinically approved nanocarriers that incorporate molecules to selectively bind and target cancer cells. This review examines some of the approved formulations and discusses the challenges in translating basic research to the clinic. We detail the arsenal of nanocarriers and molecules available for selective tumour targeting, and emphasize the challenges in cancer treatment.
7,443 citations
"Gold Nanostructures as a Platform f..." refers background in this paper
...The first generation of NP-based therapies approved by the FDA consists of lipid based NP-systems, such as liposomes and micelles [9]....
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TL;DR: It is found that, after exposure to continuous red laser at 800 nm, malignant cells require about half the laser energy to be photothermally destroyed than the nonmalignant cells, so both efficient cancer cell diagnostics and selective photothermal therapy are realized at the same time.
Abstract: Due to strong electric fields at the surface, the absorption and scattering of electromagnetic radiation by noble metal nanoparticles are strongly enhanced. These unique properties provide the potential of designing novel optically active reagents for simultaneous molecular imaging and photothermal cancer therapy. It is desirable to use agents that are active in the near-infrared (NIR) region of the radiation spectrum to minimize the light extinction by intrinsic chromophores in native tissue. Gold nanorods with suitable aspect ratios (length divided by width) can absorb and scatter strongly in the NIR region (650−900 nm). In the present work, we provide an in vitro demonstration of gold nanorods as novel contrast agents for both molecular imaging and photothermal cancer therapy. Nanorods are synthesized and conjugated to anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies and incubated in cell cultures with a nonmalignant epithelial cell line (HaCat) and two malignant oral epithelial ...
5,047 citations
"Gold Nanostructures as a Platform f..." refers background or methods in this paper
...El-sayed and coworkers have demonstrated in vitro that the GNRs can be used as novel contrast agents for both molecular imaging and PTT as illustrated in Figure 7 [14]....
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...Among other gold nanostructures, GNRs provide enough contrast for simultaneous molecular imaging and PTT due to their strong absorption and scattering in the visible and NIR region [14,96,122,123]....
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...Recent studies have shown that GNPs could effectively damage the targeted tumor tissue when irradiated with wavelengths around their absorption peak [14,96,112-114]....
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TL;DR: PDT is being tested in the clinic for use in oncology — to treat cancers of the head and neck, brain, lung, pancreas, intraperitoneal cavity, breast, prostate and skin.
Abstract: The therapeutic properties of light have been known for thousands of years, but it was only in the last century that photodynamic therapy (PDT) was developed. At present, PDT is being tested in the clinic for use in oncology--to treat cancers of the head and neck, brain, lung, pancreas, intraperitoneal cavity, breast, prostate and skin. How does PDT work, and how can it be used to treat cancer and other diseases?
5,041 citations
TL;DR: The intracellular uptake of different sized and shaped colloidal gold nanoparticles is investigated and it is shown that kinetics and saturation concentrations are highly dependent upon the physical dimensions of the nanoparticles.
Abstract: We investigated the intracellular uptake of different sized and shaped colloidal gold nanoparticles. We showed that kinetics and saturation concentrations are highly dependent upon the physical dimensions of the nanoparticles (e.g., uptake half-life of 14, 50, and 74 nm nanoparticles is 2.10, 1.90, and 2.24 h, respectively). The findings from this study will have implications in the chemical design of nanostructures for biomedical applications (e.g., tuning intracellular delivery rates and amounts by nanoscale dimensions and engineering complex, multifunctional nanostructures for imaging and therapeutics).
4,383 citations
"Gold Nanostructures as a Platform f..." refers background in this paper
...It is believed that the size of the NPs plays a big role in their uptake at the cellular level leading to different sensitization properties [12,16]....
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TL;DR: While nanorods with a higher aspect ratio along with a smaller effective radius are the best photoabsorbing nanoparticles, the highest scattering contrast for imaging applications is obtained from nanorod of high aspect ratio with a larger effective radius.
Abstract: The selection of nanoparticles for achieving efficient contrast for biological and cell imaging applications, as well as for photothermal therapeutic applications, is based on the optical properties of the nanoparticles. We use Mie theory and discrete dipole approximation method to calculate absorption and scattering efficiencies and optical resonance wavelengths for three commonly used classes of nanoparticles: gold nanospheres, silica−gold nanoshells, and gold nanorods. The calculated spectra clearly reflect the well-known dependence of nanoparticle optical properties viz. the resonance wavelength, the extinction cross-section, and the ratio of scattering to absorption, on the nanoparticle dimensions. A systematic quantitative study of the various trends is presented. By increasing the size of gold nanospheres from 20 to 80 nm, the magnitude of extinction as well as the relative contribution of scattering to the extinction rapidly increases. Gold nanospheres in the size range commonly employed (∼40 nm)...
4,065 citations
"Gold Nanostructures as a Platform f..." refers background in this paper
...Calculated absorption and scattering coefficients for spherical GNPs, GNRs, and GNSs are given in supplementary Table S2 [121]....
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