Gold Nanoparticles For Photothermal Therapy Research Articles

Gold nanoparticles for photothermal therapy – Influence of experimental conditions on the properties of resulting AuNPs

Gold nanoparticles (AuNPs)-mediated Photothermal Therapy (PTT) is a minimally-invasive therapeutic approach that uses AuNPs to convert light into heat, leading to the thermal ablation of tumors. Thus, the efficacy of this strategy strongly relies on the photothermal conversion potential of AuNPs. The ability to convert light into heat can be enhanced by tuning the physicochemical and optical properties of AuNPs. This can be achieved by changing the conditions of AuNP's synthesis, such as the order of addition of reagents. The present work entails to explore how varying the order of reagents addition modulates the properties of AuNPs, particularly enhancing the photothermal conversion potential of the resulting AuNPs and consequently, improving PTT efficacy. For this, eleven different AuNPs' nanoformulations were synthetized following different sequences of addition of reagents. These nanoformulations were characterized regarding their physicochemical properties namely size, surface charge, gold concentration, surface morphology and maximum absorbance wavelength. In addition, their thermal activation profiles were determined in vitro. Furthermore, the biocompatibility of different nanoformulations was also assessed. Three nanoformulations, with the most favorable photothermal activation profiles (AuNPs 2, 3 and 7), were then selected for preliminary in vitro safety and efficacy assays using a panel of cell lines. These three nanoformulations were deemed safe in vitro at the tested concentrations. At 250 μM of gold content, and after an incubation period of 4 h, followed by 5 min irradiation with a laser emitting at 808 nm (7.96 W/cm2), AuNPs 7 significantly reduced the cell viability of all cancer cell lines tested (MCF-7, HCT-116 and A375) by ≥ 45 %. However, such cytotoxic effect was not observed for the human keratinocyte cell line (HaCat), thus demonstrating its specificity towards cancer cells. Overall, the results herein presented reinforce that the order of reagents addition is highly important for achieving adequate AuNPs for PTT.

Development of Hollow Gold Nanoparticles for Photothermal Therapy and Their Cytotoxic Effect on a Glioma Cell Line When Combined with Copper Diethyldithiocarbamate.

Gold-based nanoparticles hold promise as functional nanomedicines, including in combination with a photothermal effect for cancer therapy in conjunction with chemotherapy. Here, we synthesized hollow gold nanoparticles (HGNPs) exhibiting efficient light absorption in the near-IR (NIR) region. Several synthesis conditions were explored and provided monodisperse HGNPs approximately 95-135 nm in diameter with a light absorbance range of approximately 600-720 nm. The HGNPs were hollow and the surface had protruding structures when prepared using high concentrations of HAuCl4. The simultaneous nucleation of a sacrificial AgCl template and Au nanoparticles may affect the resulting HGNPs. Diethyldithiocarbamate (DDTC) is metabolized from disulfiram and is a repurposed drug currently attracting attention. The chelation of DDTC with copper ion (DDTC-Cu) has been investigated for treating glioma, and here we confirmed the cytotoxic effect of DDTC-Cu towards rat C6 glioma cells in vitro. HGNPs alone were biocompatible and showed little cytotoxicity, whereas a mixture of DDTC-Cu and HGNPs was cytotoxic in a dose dependent manner. The temperature of HGNPs was increased by NIR-laser irradiation. The photothermal effect on HGNPs under NIR-laser irradiation resulted in cytotoxicity towards C6 cells and was dependent on the irradiation time. Photothermal therapy by HGNPs combined and DDTC-Cu was highly effective, suggesting that this combination approach hold promise as a future glioma therapy.

Rational approach to design gold nanoparticles for photothermal therapy: the effect of gold salt on physicochemical, optical and biological properties

Among the unique characteristics associated to gold nanoparticles (AuNPs) in biomedicine, their ability to convert light energy into heat opens ventures for improved cancer therapeutic options, such as photothermal therapy (PTT). PTT relies on the local hyperthermia of tumor cells upon irradiation with light beams, and the association of AuNPs with radiation within the near infrared (NIR) range constitutes an advantageous strategy to potentially improve PTT efficacy. Herein, it was explored the effect of the gold salt on the AuNPs’ physicochemical and optical properties. Mostly spherical-like negatively charged AuNPs with variable sizes and absorbance spectra were obtained. In addition, photothermal features were assessed using in vitro phantom models. The best formulation showed the ability to increase their temperature in aqueous solution up to 19 °C when irradiated with a NIR laser for 20 min. Moreover, scanning transmission electron microscopy confirmed the rearrangement of the gold atoms in a face-centered cubic structure, which further allowed to calculate the photothermal conversion efficiency upon combination of theoretical and experimental data. AuNPs also showed local retention after being locally administered in in vivo models. These last results obtained by computerized tomography allow to consider these AuNPs as promising elements for a PTT system. Moreover, AuNPs showed high potential for PTT by resulting in in vitro cancer cells’ viability reductions superior to 70 % once combine with 5 min of NIR irradiation.

Hybrid chitosan gold nanoparticles for photothermal therapy and enhanced cytotoxic action of 6-mercaptopurine on breast cancer cell line

BackgroundOne of the most popular anti-inflammatory and anti-leukemic medications is 6-mercaptopurine, along with its riboside derivatives. Because of their potent adverse effects and limited biological half-life, they are rarely used. These problems might be solved by a novel medication delivery technique based on gold nanoparticles (AuNPs). In present work, gold/chitosan nanohybrid was manufactured and assessed for photothermal therapy as well as a drug carrier to minimize the unwanted harmful effects of 6-Mercaptopurine (6-MP). We estimate loading of 6-MP on gold nanoparticles by chitosan reduction (Au@CS NPs) creating (Au@CS-6MP).ResultsAuNPs were green sensitized in one step via chitosan. UV–visible spectroscopy, Zeta potential, TEM, FTIR spectroscopy, and HPLC technique for loading efficiency were used to characterize AuNPs and Au@CS-6MPC NPS. Our results estimate that AuNPs and Au@CS-6MPC NPS with small sizes of 16 ± 2 and 20 ± 4 nm, respectively, and Zeta potential 53.6 ± 5.2 and 55 ± 3 mV, respectively, and loading efficiency of 52% were achieved. Cytotoxicity of the Au@CS-6MPC NPs was significantly increased compared to free 6MP with IC50 1.11 µM. Cell viability was inhibited in AuNPs exposed to DPSS laser light, reaching 10% inhibition after 8 min.ConclusionsThe prepared Au@CS-6MPC NPs resulted in an additive effect in therapeutic managing of breast cancer. It can be predicted that this nanocomposite along with synergistic effect of laser light will definitely result in better therapeutic efficacy and reduced side effects of 6-MP in a combination photothermal chemotherapy treatment. This combination can be explored as future alternative for cancer therapy.

Indocyanine-type Infrared-820 Encapsulated Polymeric Nanoparticle-Assisted Photothermal Therapy of Cancer.

Organic small-molecule photosensitizers are well-characterized and known for the light-responsive treatment modality including photodynamic therapy. Compared with ultraviolet–visible (UV–vis) light used in conventional photodynamic therapy with organic photosensitizers, near-infrared (NIR) light from 700 to 900 nm is less absorbed and scattered by biological tissue such as hemoglobin, lipids, and water, and thus, the use of NIR excitation can greatly increase the penetration depth and emission. Additionally, NIR light has lower energy than UV–vis that can be beneficial due to less activation of fluorophores present in tissues upon NIR irradiation. However, the low water stability, nonspecific distribution, and short circulation half-life of the organic photosensitizers limit its broad biological application. NIR responsive small-molecule fluorescent agents are the focus of extensive research for combined molecular imaging and hyperthermia. Recently a new class of NIR dye, IR-820 with excitation and emission wavelengths of 710 and 820 nm, has been developed and explored as an alternative platform to overcome some of the limitations of the most commonly used gold nanoparticles for photothermal therapy of cancer. Herein, we synthesized a core–shell biocompatible nanocarrier envelope made up of a phospholipid conjugated with poly(ethylene glycol) as a shell, while poly(lactic glycolic acid) (PLGA) was used as a core to encapsulate IR-820 dye. The IR-820-loaded nanoparticles were prepared by nanoprecipitation and characterized for their physicochemical properties and photothermal efficiency. These nanoparticles were monodispersed and highly stable in physiological pH with the hydrodynamic size of 103 ± 8 nm and polydispersity index of 0.163 ± 0.031. The IR-820-loaded nanocarrier showed excellent biocompatibility in the dark, whereas remarkable phototoxicity was observed with breast cancer cells (MCF-7) upon NIR laser excitation. Therefore, the IR-820-loaded phospholipid mimicking biodegradable lipid-polymer composite nanoparticles could have great potential for cancer theranostics.

Optimization of Nonspherical Gold Nanoparticles for Photothermal Therapy

Previous investigations devoted to the optimization of nonspherical gold nanoparticles for photothermal therapy (PTT) encountered two issues, namely, the appropriate selection of objective functions and the processing of particle random orientations. In this study, these issues were resolved, and accurate optimization results were obtained for the three typical nonspherical gold nanoparticles (nanospheroid, nanocylinder, and nanorod) by using the T-matrix method. The dependence of the optimization results on the excitation wavelength and the refractive index of tissue was investigated. Regardless of the excitation wavelength and tissue type, gold nanospheroids were found to be the most effective therapeutic agents for PTT. The light absorption ability of optimized nanoparticles could be enhanced by using a laser with a longer wavelength. Finally, the design tolerance for the different sizes of nanoparticles was provided.

Photothermal Therapy: Light‐Triggered Assembly of Gold Nanoparticles for Photothermal Therapy and Photoacoustic Imaging of Tumors In Vivo (Adv. Mater. 6/2017)

Photothermal Therapy: Light‐Triggered Assembly of Gold Nanoparticles for Photothermal Therapy and Photoacoustic Imaging of Tumors In Vivo (Adv. Mater. 6/2017)

Light-Triggered Assembly of Gold Nanoparticles for Photothermal Therapy and Photoacoustic Imaging of Tumors In Vivo.

Photocross-linkable Au nanoparticles are prepared through surface decoration of photolabile diazirine moieties. Both in vitro and in vivo studies indicate that the light-triggered cross-linking can dramatically shift the surface plasmon resonance of Au nanoparticles to near-infrared regions, which in consequence remarkably enhances their efficacy for photothermal therapy and photoacoustic imaging of tumors in vivo.

Bioproduction of gold nanoparticles for photothermal therapy.

Photothermal response of plasmonic nanomaterials can be utilized for a number of therapeutic applications such as the ablation of solid tumors. Gold nanoparticles were prepared using different methods. After optimization, we applied an aqueous plant extract as the reducing and capping agent of gold and maximized the near-infrared absorption (650-900 nm). Resultant nanoparticles showed good biocompatibility when tested in vitro in human keratinocytes and yeast Saccharomyces cerevisiae. Gold nanoparticles were easily activated by controlled temperature with an ultrasonic water bath and application of a pulsed laser. These gold nanoparticles can be synthesized with reproducibility, modified with seemingly limitless chemical functional groups, with adequate controlled optical properties for laser phototherapy of tumors and targeted drug delivery.

Tailoring the pH-induced aggregation behaviors of mixed-charge gold nanoparticles for photothermal therapy

Event Abstract Back to Event Tailoring the pH-induced aggregation behaviors of mixed-charge gold nanoparticles for photothermal therapy Huan Li1*, Xiangsheng Liu1*, Nan Huang1*, Kefeng Ren1*, Qiao Jin1* and Jian Ji1* 1 Zhejiang University, Polymer Science and Engineering, China Introduction: The acidic microenvironment of tumor tissues has proven to be one of the major differences from other normal tissues. The near-infrared (NIR) light irradiation of aggregated gold nanoparticles in a tumor acidic pH-induced manner could then provide an effect approach to treat solid tumors with the advantage of minimizing the undesired damage to normal tissues[1][2]. Although it is well known the aggregation of larger nanoparticles will results in better NIR photothermal effect, the preparation of pH-sensitive gold nanoparticles in large sizes remain big challenging due to their worse colloidal stability. In this paper, we introduce a facile way to endow gold nanoparticles(GNPs) especially those large ones with tunable pH-aggregation behaviors by modifying the nanoparticle surface with mixed-charge self-assembly monolayers(SAMs) compromising positively and negatively charged thiol ligands. Fig 1. Schematic illustration of MC-GNPs aggregation in a tumor acidic pH-induced manner for photothermal cancer therapy.(Adapted with permission.[3] Copyright 2014, American Chemical Society.) Materials and Methods: pH-sensitive mixed-charge gold nanoparticles (MC-GNPs) were prepared by modifying the GNPs’ surface with mixed SAMs of weak electrolytic 11-mercaptoundecanoic acid (MUA) and strong electrolytic (10-mercaptodecyl) trimethyl-ammonium bromide (TMA). The influence of nanoparticle size (four different sizes were chosen, that is 15 nm, 21nm, 33nm, 53 nm) and surface ligand composition on the pH-induced aggregation behaviors of MC-GNPs were systematically studied. Finally, four different size MC-GNPs that all responded to tumor acidic pH were prepared and their photothermal therapy efficacy was carefully examined. Results and Discussion: Four different size MC-GNPs with the same surface ligand composition were prepared to study the influence of nanoparticle size on pH-sensitive aggregation behaviors of MC-GNPs. The MC-GNPs in different sizes showed diverse pH-induced aggregation behaviours. That is, as the nanoparticle size increases, the MC-GNPs will aggregate at a higher pH, and vice versa. Next, the same size MC-GNPs with different surface ligand composition were prepared to study the influence of surface ligand composition on pH-sensitive aggregation behaviors of MC-GNPs. By increasing the proportion of MUA in the SAMs, MC-GNPs which aggregated at lower pH were attained, and the opposite was also true. With proper surface ligand composition, the MC-GNPs in four different sizes that all exhibited aggregation at tumor acidic pH were obtained. Among them, the biggest MC-GNPs showed the most encouraging aggregation-enhanced photothermal efficacy in vitro when they formed aggregates. The mixed-charge self-assembled monolayers were then proved as a facile method to design pH-induced aggregation of large gold nanoparticles for better NIR photothermal cancer therapy. Conclusion:In summary, we systematically explored the basic law of the pH-induced aggregation of MC-GNPs influenced by nanoparticle size and surface charge composition. Given this, we can synthesize certain size MC-GNPs with desired pH-induced aggregation behaviours. In this study, we prepared four different size MC-GNPs that all respond to tumor acidic pH. The aggregates from the largest MC-GNPs showed the most encouraging photothermal therapy efficacy, which implies that mixed-charge surface modification is a facile way to endow nanoparticles with desired pH-sensitivity to better their therapeutic efficiency, especially for those large size ones. Financial support from the National Science Fund for Distinguished Young Scholars (51025312), the National Basic Research Program of China (2011CB606203), NSFC-50830106 and 21174126, Open Project of State Key Laboratory of Supramolecular Structure and Materials (SKLSSM 201204), and Research Fund for the Doctoral Program of Higher Education of China (20110101110037, 20110101120049, and 20120101130013) is gratefully acknowledged.

Green synthesis of anisotropic gold nanoparticles for photothermal therapy of cancer.

Nanoparticles of varying composition, size, shape, and architecture have been explored for use as photothermal agents in the field of cancer nanomedicine. Among them, gold nanoparticles provide a simple platform for thermal ablation owing to its biocompatibility in vivo. However, the synthesis of such gold nanoparticles exhibiting suitable properties for photothermal activity involves cumbersome routes using toxic chemicals as capping agents, which can cause concerns in vivo. Herein, gold nanoparticles, synthesized using green chemistry routes possessing near-infrared (NIR) absorbance facilitating photothermal therapy, would be a viable alternative. In this study, anisotropic gold nanoparticles were synthesized using an aqueous route with cocoa extract which served both as a reducing and stabilizing agent. The as-prepared gold nanoparticles were subjected to density gradient centrifugation to maximize its NIR absorption in the wavelength range of 800-1000 nm. The particles also showed good biocompatibility when tested in vitro using A431, MDA-MB231, L929, and NIH-3T3 cell lines up to concentrations of 200 μg/mL. Cell death induced in epidermoid carcinoma A431 cells upon irradiation with a femtosecond laser at 800 nm at a low power density of 6 W/cm(2) proved the suitability of green synthesized NIR absorbing anisotropic gold nanoparticles for photothermal ablation of cancer cells. These gold nanoparticles also showed good X-ray contrast when tested using computed tomography (CT), proving their feasibility for use as a contrast agent as well. This is the first report on green synthesized anisotropic and cytocompatible gold nanoparticles without any capping agents and their suitability for photothermal therapy.

Anti-CD30-targeted gold nanoparticles for photothermal therapy of L-428 Hodgkin’s cell [Erratum

Anti-CD30-targeted gold nanoparticles for photothermal therapy of L-428 Hodgkin’s cell [Erratum

Anti-CD30-targeted gold nanoparticles for photothermal therapy of L-428 Hodgkin's cell

PurposeDue to the efficient bioconjugation and highly photothermal effect, gold nanoparticles can stain receptor-overexpressing cancer cells through specific targeting of ligands to receptors, strongly absorb specific light and efficiently convert it into heat based on the property of surface plasmon resonance, and then induce the localized protein denaturation and cell death.MethodsTwo gold nanoparticle–antibody conjugates, gold-BerH2 antibody (anti-CD30 receptor) and gold-ACT1 antibody (anti-CD25-receptor), were synthesized. Gold-BerH2 conjugates can specifically bind to the surface of L-428 Hodgkin’s cells, and gold-ACT1 conjugates were used for the control. The gold nanoparticle-induced L-428 cell-killing experiments were implemented with different experimental parameters.ResultsAt a relatively low concentration of gold and short incubation time, the influence of cytotoxicity of gold on cell viability can be overlooked. Under laser irradiation at suitable power, the high killing efficiency of gold-targeted L-428 cells was achieved, but little damage was done to nontargeted cancer cells.ConclusionGold nanoparticle-mediated photothermal therapy provides a relatively safe therapeutic technique for cancer treatment.

Specific Cell Targeting with Nanobody Conjugated Branched Gold Nanoparticles for Photothermal Therapy

Branched gold nanoparticles are potential photothermal therapy agents because of their large absorption cross section in the near-infrared window. Upon laser irradiation they produce enough heat to destroy tumor cells. In this work, branched gold nanoparticles are biofunctionalized with nanobodies, the smallest fully functional antigen-binding fragments evolved from the variable domain, the VHH, of a camel heavy chain-only antibody. These nanobodies bind to the HER2 antigen which is highly expressed on breast and ovarian cancer cells. Flow cytometric analysis and dark field images of HER2 positive SKOV3 cells incubated with anti-HER2 conjugated branched gold nanoparticles show specific cell targeting. Laser irradiation studies reveal that HER2 positive SKOV3 cells exposed to the anti-HER2 targeted branched gold nanoparticles are destroyed after five minutes of laser treatment at 38 W/cm(2) using a 690 nm continuous wave laser. Starting from a nanoparticle optical density of 4, cell death is observed, whereas the control samples, nanoparticles with anti-PSA nanobodies, nanoparticles only, and laser only, do not show any cell death. These results suggest that this new type of bioconjugated branched gold nanoparticles are effective antigen-targeted photothermal therapeutic agents for cancer treatment.