Determination of the minimum temperature required for selective photothermal destruction of cancer cells with the use of immunotargeted gold nanoparticles

Laser photothermal therapy of cancer with the use of gold nanoparticles immunotargeted to molecular markers on the cell surface has been shown to be an effective modality to selectively kill cancer cells at much lower laser powers than those needed for healthy cells. To elucidate the minimum light dosimetry required to induce cell death, photothermal destruction of two cancerous cell lines and a noncancerous cell line treated with antiepidermal growth factor receptor (anti-EGFR) antibody-conjugated gold nanoparticles is studied, and a numerical heat transport model is used to estimate the local temperature rise within the cells as a result of the laser heating of the gold nanoparticles. It is found that cell samples with higher nanoparticle loading require a lower incident laser power to achieve a certain temperature rise. Numerically estimated temperatures of 70-80 degrees C achieved by heating the gold particles agree well with the measured threshold temperature for destruction of the cell lines by oven heating and those measured in an earlier nanoshell method. Specific binding of anti-EGFR antibody to cancerous cells overexpressing EGFR selectively increases the gold nanoparticle loading within cancerous cells, thus allowing the cancerous cells to be destroyed at lower laser power thresholds than needed for the noncancerous cells. In addition, photothermal therapy using gold nanoparticles requires lower laser power thresholds than therapies using conventional dyes due to the much higher absorption coefficient of the gold nanoparticles.     

Photothermal ablation therapy for cancer based on metal nanostructures

Besides conventional surgery, radiation therapy, and chemotherapy, which all tend to have side-effects and damage normal tissues, new medical strategies, such as photothermal sensitization and photo-thermal ablation therapy (PTA) with near-IR laser light, have been explored for treating cancer. Much of the current excitement surrounding nanoscience is directly connected to the promise of new nanotechnology for cancer diagnosis and therapy. The basic principle behind PTA is that heat generated from light can be used to destroy cancer cells. Strong optical absorption and high efficiency of photothermal conversion at the cancer sites are critical to the success of PTA. Because of their unique optical properties, e.g., strong surface plasmon resonance (SPR) absorption, noble metal nanomaterials, such as gold and silver, have been found to significantly enhance photothermal conversion for PTA applications. Substantial effort has been made to develop metal nanostructures with optimal structural and photothermal properties. Ideal metal nanostructures should have strong and tunable SPR, be easy to deliver, have low toxicity, and be convenient for bioconjugation for actively targeting specific cancer cells. This review would highlight some gold nanostructures with various shapes and properties, including nanoparticles (NPs), nanorods (NRs), nanoshells, nanocages, and hollow nanospheres, which have been studied for PTA applications. Among these structures, hollow gold nanospheres (HGNs) exhibit arguably the best combined properties because of their small size (30―50 nm), spherical shape, and strong, narrow, and tunable SPR absorption.     

Ultrasmall reduced graphene oxide with high near-infrared absorbance for photothermal therapy

We developed nanosized, reduced graphene oxide (nano-rGO) sheets with high near-infrared (NIR) light absorbance and biocompatibility for potential photothermal therapy. The single-layered nano-rGO sheets were ～20 nm in average lateral dimension, functionalized noncovalently by amphiphilic PEGylated polymer chains to render stability in biological solutions and exhibited 6-fold higher NIR absorption than nonreduced, covalently PEGylated nano-GO. Attaching a targeting peptide bearing the Arg-Gly-Asp (RGD) motif to nano-rGO afforded selective cellular uptake in U87MG cancer cells and highly effective photoablation of cells in vitro. In the absence of any NIR irradiation, nano-rGO exhibited little toxicity in vitro at concentrations well above the doses needed for photothermal heating. This work established nano-rGO as a novel photothermal agent due to its small size, high photothermal efficiency, and low cost as compared to other NIR photothermal agents including gold nanomaterials and carbon nanotubes.     

无种子法纳米金棒的制备及其对肿瘤细胞光热治疗效应研究

采用简便快捷的无种子法一步完成了纳米金棒的制备.通过改变实验条件可以调控纳米金棒的吸收峰从可见到近红外转移.将巯基聚乙二醇(PEG-SH)置换金棒表面的十六烷基三甲基溴化铵(CTAB)分子,大大提高了金棒的生物相容性.制备的纳米金棒在近红外(NIR)光照射下对肿瘤细胞有很好的杀伤效果.研究结果为纳米金棒用于抗肿瘤治疗提供了实验基础.     

A new photothermal therapeutic agent: core-free nanostructured Au x Ag1-x dendrites

A new class of Au(x)Ag(1-x) nanostructures with dendrite morphology and a hollow interior were synthesized by using a replacement reaction between Ag dendrites and an aqueous solution of HAuCl(4). The Ag nanostructured dendrites were generated by the reaction of AgNO(3) with ascorbic acid in a methanol/water system. The dendrites resemble a coral shape and are built up of many stems with an asymmetric arrangement. Each stem is approximately 400 nm in length and 65 nm in diameter. The bimetallic composition of Au(x)Ag(1-x) can be tuned by the addition of different amounts of HAuCl(4) to the Ag dendritic solution. The hollowing process resulted in tubular structures with a wall thickness of 10.5 nm in Au(0.3)Ag(0.7) dendrites. The UV/Vis spectra indicate that the strongest NIR absorption among the resulting hollow Au(x)Ag(1-x) dendrites was in Au(0.3)Ag(0.7). The MTT assay was conducted to evaluate the cytotoxicity of Ag dendrites, hollow Au(0.06)Ag(0.94) and Au(0.3)Ag(0.7) dendrites, and Au nanorods. It was found that hollow Au(0.06)Ag(0.94) and Au(0.3)Ag(0.7) dendrites exhibited good biocompatibility, while both Ag dendrites and Au nanorods showed dose-dependent toxicity. Because of absorption in the NIR region, hollow Au(0.3)Ag(0.7) dendrites were used as photothermal absorbers for destroying A549 lung cancer cells. Their photothermal performance was compared to that of Au nanorod photothermal therapeutic agents. As a result, the particle concentration and laser power required for efficient cancer cell damage were significantly reduced for hollow Au(0.3)Ag(0.7) dendrites relative to those used for Au nanorods. The hollow Au(0.3)Ag(0.7) nanostructured dendrites show potential in photothermolysis for killing cancer cells.     

无种子法纳米金棒的制备及其对肿瘤细胞光热治疗效应研究

采用简便快捷的无种子法一步完成了纳米金棒的制备. 通过改变实验条件可以调控纳米金棒的吸收峰从可见到近红外转移. 将巯基聚乙二醇（PEG-SH）置换金棒表面的十六烷基三甲基溴化铵（CTAB）分子,大大提高了金棒的生物相容性. 制备的纳米金棒在近红外（NIR）光照射下对肿瘤细胞有很好的杀伤效果.研究结果为纳米金棒用于抗肿瘤治疗提供了实验基础.     

适体功能化的金纳米棒用于癌症靶向治疗的研究进展

金纳米棒(gold nanorods,GNRs)具有特殊的光学性质、较大的比表面积、出色的光热转换性能、表面易修饰等特点,在药物递送、光疗、生物成像和化学传感等领域应用十分广泛。适体是短的单链DNA或RNA片段,可特异性识别癌细胞或其表面的膜蛋白。近年来,适体功能化的GNRs在癌症靶向治疗领域显示出良好的应用前景。根据GNRs对癌症作用机制的差异,本文从光热疗法、光动力疗法、化疗和联合疗法4个方面总结了适体功能化的GNRs在癌症靶向治疗中的最新进展,并对该领域面临的主要挑战和发展趋势进行了探讨与展望。     

“Two‐Step” Raman Imaging Technique To Guide Chemo‐Photothermal Cancer Therapy

Graphene oxide‐wrapped gold nanorods (GO@AuNRs) offer efficient drug delivery as well as NIR laser photothermal therapy (PTT) in vitro and in vivo. However, no real‐time observation of drug release has been reported to better understand the synergy of chemotherapy and PTT. Herein, surface‐enhance Raman spectroscopy (SERS) is employed to guide chemo‐photothermal cancer therapy by a two‐step mechanism. In the presence of GO as an internal standard, SERS signals of DOX (doxorubicin) loaded onto GO@AuNRs are found to be pH‐responsive. Both DOX and GO show strong SERS signals before the DOX@GO@AuNRs are endocytic. However, when the DOX@GO@AuNRs enter acidic microenvironments such as endosomes and/or lysosomes, the DOX signals start decreasing while the GO signals remain the same. This plasmonic antenna could be used to identify the appropriate time to apply the PTT laser during chemo‐photothermal therapy.     

Polypyrrole nanoparticles for high-performance in vivo near-infrared photothermal cancer therapy

Polypyrrole nanoparticles (PPy NPs) exhibit strong absorption in the near infrared (NIR) region. With an excellent photothermal efficiency of ～45% at 808 nm, sub-100 nm PPy NPs are demonstrated to be a promising photothermal agent for in vivo cancer therapy using NIR irradiation.     

One‐Dimensional Fe2P Acts as a Fenton Agent in Response to NIR II Light and Ultrasound for Deep Tumor Synergetic Theranostics

The stringent reaction conditions for an effective Fenton reaction (pH range of 3–4) hinders its application in cancer therapy. Therefore, how to improve the efficiency of the Fenton reaction in a tumor site has been the main obstacle in chemodynamic therapy (CDT). Herein, we report biocompatible one‐dimensional (1D) ferrous phosphide nanorods (FP NRs) with ultrasound (US)‐ and photothermal (PT)‐enhanced Fenton properties and excellent photothermal conversion efficiency (56.6 %) in the NIR II window, showing synergistic therapeutic properties. Additionally, the high photothermal conversion efficiency and excellent traverse relaxivity (277.79 mm ^?1 s^?1) of the FP NRs means they are excellent photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) agents. This is the first report on exploiting the response of metallic phosphides to NIR II laser (1064 nm) and ultrasound to improve the CDT effect with a high therapeutic effect and PA/MR imaging.     

LyP-1 peptide-functionalized gold nanoprisms for SERRS imaging and tumor growth suppressing by PTT induced-hyperthermia

The gold nanoprisms (GNPs) have exhibited special plasmonic properties for biomedical applications because of their unique shapes and dimensions. Based on their optical performance, the NIR dye IR780 not only enabled the GNPs-based nanosystem as SERRS nanoparticles for Raman-encoded molecular imaging, but also enhanced the plasmonic photothermal property by laser irradiation. Meanwhile, the GNPs/IR780-Lyp-1 by introduction of tumor-homing peptide segment LyP-1, which presents high affinity to p32 protein, demonstrated the increased enrichment in tumor region and enhanced photothermal therapy efficacy.     

金纳米花介导的近红外热疗对人喉癌Hep-2细胞增殖的抑制作用

采用弱配体柠檬酸钠修饰的金纳米花为介导材料,考察了其对人喉癌Hep-2细胞的NIR热疗作用,结果表明,这种金纳米花材料具有良好的NIR光热转换性能,可有效抑制Hep-2细胞增殖.     

Controlled-release system mediated by a retro Diels-Alder reaction induced by the photothermal effect of gold nanorods

Controlled-release systems that respond to external stimuli have received great interest for use in medical treatments such as for drug delivery to specific sites. Gold nanorods have an absorption band at the near-infrared region and convert the absorbed light energy into heat, which is known as a "photothermal effect". Therefore, gold nanorods are expected to act not only as an on-demand thermal converter for photothermal therapy but also as a controller of a drug-release system capable of responding to the near-infrared light irradiation. In this study, to construct a controlled-release system that responds to near-infrared light irradiation, we modified gold nanorods with polyethylene glycol (PEG) through Diels-Alder cycloadducts. When the modified gold nanorods were irradiated by near-infrared light, the PEG chains were released from the gold nanorods because of the retro Diels-Alder reaction induced by the photothermal effect. As a result of the PEG release, the gold nanorods formed aggregates. This type of controlled-release system coupled with the aggregate formation of the gold nanorods triggered by near-infrared light could be expanded to applications of gold nanorods in medical fields such as drug and photothermal therapy.     

基于金纳米棒的生物检测、细胞成像和癌症的光热治疗

由于金纳米棒颗粒独特的可调的表面等离子共振特性,使得金纳米棒颗粒在纳米复合材料和功能化纳米器件的构建、纳米生物技术、生物医学等领域具有广泛而重要的应用前景。本文综述了金纳米棒颗粒的生物检测、细胞成像和癌症的光热治疗方面的最新研究进展,并介绍了金纳米棒颗粒的光学性质和金纳米棒颗粒和几种主要的表面修饰方法,对金纳米棒颗粒在生物应用过程中存在的主要问题进行了讨论。     

Spindle‐Like Polypyrrole Hollow Nanocapsules as Multifunctional Platforms for Highly Effective Chemo–Photothermal Combination Therapy of Cancer Cells in Vivo

The monodispersed spindle‐like polypyrrole hollow nanocapsules (PPy HNCs) as the multifunctional platforms for combining chemotherapy with photothermal therapy for cancer cells are reported. Whereas the hollow cavity of nanocapsules can be used to load the anticancer drug (i.e., doxorubicin) for chemotherapy, the PPy shells can convert NIR light into heat for photothermal therapy. The release of the drug from the spindle‐like PPy HNCs is pH‐sensitive and near‐infrared (NIR) light‐enhanced. More importantly, the spindle‐like PPy HNCs can penetrate cells more rapidly and efficiently in comparison with the spherical PPy HNCs. Both in vitro and in vivo experiments demonstrated that the combination of DOX‐loaded spindle‐like PPy HNCs and NIR light provide a highly effective and feasible chemo‐photothermal therapy cancer method with a synergistic effect. Owing to their high photothermal conversion efficiency, large hollow cavity, and good biocompatibility, the spindle‐like PPy HNCs could be used as a promising new cancer drug‐nanocarrier and photothermal agent for localized tumorous chemo‐photothermal therapy.     

Synthesis and optical properties of small Au nanorods using a seedless growth technique

Gold nanoparticles have shown potential in photothermal cancer therapy and optoelectronic technology. In both applications, a call for small size nanorods is warranted. In the present work, a one-pot seedless synthetic technique has been developed to prepare relatively small monodisperse gold nanorods with average dimensions (length × width) of 18 × 4.5 nm, 25 × 5 nm, 15 × 4.5 nm, and 10 × 2.5 nm. In this method, the pH was found to play a crucial role in the monodispersity of the nanorods when the NaBH(4) concentration of the growth solution was adjusted to control the reduction rate of the gold ions. At the optimized pH and NaBH(4) concentrations, smaller gold nanorods were produced by adjusting the CTAB concentration in the growth solution. In addition, the concentration of silver ions in the growth solution was found to be pivotal in controlling the aspect ratio of the nanorods. The extinction coefficient values for the small gold nanorods synthesized with three different aspect ratios were estimated using the absorption spectra, size distributions, and the atomic spectroscopic analysis data. The previously accepted relationships between the extinction coefficient or the longitudinal band wavelength values and the nanorods' aspect ratios found for the large nanorods do not extend to the small size domain reported in the present work. The failure of extending these relationships over larger sizes is a result of the interaction of light with the large rods giving an extinction band which results mostly from scattering processes while the extinction of the small nanorods results from absorption processes.     

Plasmonic nanopowders for photothermal therapy of tumors

We describe a novel strategy for the fabrication of plasmonic nanopowders (dried gold nanoparticles) by using wet chemical nanoparticle synthesis, PEG-SH functionalization, and a standard freeze-drying technique. Our strategy is illustrated by successful fabrication of different plasmonic nanopowders, including gold nanorods, gold-silver nanocages, and gold nanospheres. Importantly, the dried nanoparticles can be stored for a long time under usual conditions and then can easily be dissolved in water at a desired concentration without such hard manipulations as sonication or heating. Redispersed samples maintain the plasmonic properties of parent colloids and do not form aggregates. These properties make pegylated freeze-dried gold nanoparticles attractive candidates for plasmonic photothermal therapy in clinical settings. In this work, redispersed gold nanorods were intravenously administered to mice bearing Ehrlich carcinoma tumors at doses of 2 and 8 mg (Au)/kg (animal). Particle biodistribution was measured by atomic absorption spectroscopy, and tumor hyperthermia effects were studied under laser NIR irradiation. Significant tumor damage was observed only at the higher dose of the nanorods.     

Multifunctional hybrid materials for combined photo and chemotherapy of cancer

Combined chemo and photothermal therapy in in vitro testing has been achieved by means of multifunctional nanoparticles formed by plasmonic gold nanoclusters with a protecting shell of porous silica that contains an antitumor drug. We propose a therapeutic nanoplatform that associates the optical activity of small gold nanoparticles aggregates with the cytotoxic activity of 20(S)-camptothecin simultaneously released for the efficient destruction of cancer cells. For this purpose, a method was used for the controlled assembly of gold nanoparticles into stable clusters with a tailored absorption cross-section in the vis/NIR spectrum, which involves aggregation in alkaline medium of 15 nm diameter gold colloids protected with a thin silica layer. Clusters were further encapsulated in an ordered homogeneous mesoporous silica coating that provides biocompatibility and stability in physiological fluids. After internalization in 42-MG-BA human glioma cells, these protected gold nanoclusters were able to produce effective photothermolysis under femtosecond pulse laser irradiation of 790 nm. Cell death occurred by combination of a thermal mechanism and mechanical disruption of the membrane cell due to induced generation of micrometer-scale bubbles by vaporizing the water inside the channels of the mesoporous silica coating. Moreover, the incorporation of 20(S)-camptothecin within the pores of the external shell, which was released during the process, provoked significant cell death increase. This therapeutic model could be of interest for application in the treatment and suppression of non-solid tumors.     

Synthesis of different-sized gold nanostars for Raman bioimaging and photothermal therapy in cancer nanotheranostics

Gold nanoparticles(AuNPs) have been attractive for nanomedicine because of their pronounced optical properties.Here,we customerized the methods to synthesize two types of gold nanostars,Au nanostars-1 and Au nanostars-2,which have different spire lengths and optical properties,and also spherical AuNPs.Compared to nanospheres,gold nanostars were less toxic to a variety of cells,including macrophages.Au nanostars-1 and Au nanostars-2 also manifested a similar pattern of tissue distribution upon in vivo administration in mice to that of nanospheres,and but reveled less liver retention than nanospheres.Due to their strong absorption in the near-infrared(NIR),Au nanostars-2 induced a strong hyperthermia effect in vitro upon excitation at 808 nm,and elicited a robust photothermal therapy(PTT) efficacy in ablating tumors in a mouse model of orthotopic breast cancer using 4T1 breast cancer cells.Meanwhile,Au nanostars-1 showed a great capability to enhance the Raman signal through surface-enhanced Raman spectroscopy(SERS) in 4T1 cells.Our combined results opened a new avenue to develop Au nanostars for cancer imaging and therapy.     

A Supramolecular Radical Dimer: High‐Efficiency NIR‐II Photothermal Conversion and Therapy

Photothermal therapy at the NIR‐II biowindow (1000–1350 nm) is drawing increasing interest because of its large penetration depth and maximum permissible exposure. Now, the supramolecular radical dimer, fabricated by N,N′‐dimethylated dipyridinium thiazolo[5,4‐d]thiazole radical cation (MPT^.+) and cucurbit[8]uril (CB[8]), achieves strong absorption at NIR‐II biowindow. The supramolecular radical dimer (2MPT^.+‐CB[8]) showed highly efficient photothermal conversion and improved stability, thus contributing to the strong inhibition on HegG2 cancer cell under 1064 nm irradiation even penetrating through chicken breast tissue. This work provides a novel approach to construct NIR‐II chromophore by tailor‐made assembly of organic radicals. It is anticipated that this study provides a new strategy to achieve NIR‐II photothermal therapy and holds promises in luminescence materials, optoelectronic materials, and also biosensing.