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.     

In vivo particle tracking and photothermal ablation using plasmon-resonant gold nanostars

Gold nanostars offer unique plasmon properties that efficiently transduce photon energy into heat for photothermal therapy. Nanostars, with their small core size and multiple long thin branches, exhibit high absorption cross-sections that are tunable in the near-infrared region with relatively low scattering effect, making them efficient photothermal transducers. Here, we demonstrate particle tracking and photothermal ablation both in vitro and in vivo. Using SKBR3 breast cancer cells incubated with bare nanostars, we observed photothermal ablation within 5 minutes of irradiation (980-nm continuous-wave laser, 15 W/cm²). On a mouse injected systemically with PEGylated nanostars for 2 days, extravasation of nanostars was observed and localized photothermal ablation was demonstrated on a dorsal window chamber within 10 minutes of irradiation (785-nm continuous-wave laser, 1.1 W/cm²). These preliminary results of plasmon-enhanced localized hyperthermia are encouraging and have illustrated the potential of gold nanostars as efficient photothermal agents in cancer therapy.From the Clinical EditorGold nanostars are tunable in the near-infrared region with low scattering, thus enable photothermal therapy. Encouraging preliminary results of plasmon-enhanced localized hyperthermia both in vitro and in vivo demonstrate that Au nanostars may be efficient photothermal agents for cancer therapy.     

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.     

Dual Responsive Hybrid Nanoparticle for Tumor Chemotherapy Combined with Photothermal Therapy

With the deepening of tumor targeting research, the application of intelligent responsive drug carriers in the field of controlled drug release has become more and more extensive, and multiple responsive nano drug carriers have attracted greater attention. In this paper, nanoparticles with gold nanorods (GNR) as the core, mesoporous silica (mSiO₂) doped with hydroxyapatite (HAP) as the inorganic hybrid shell and physically loaded with doxorubicin hydrochloride (DOX·HCl) are prepared (DOX/GNR/mSiO₂/HAP, DNPs). DNPs nanoparticles have a typical core-shell structure. The gold nanorods as the core have extremely high light-to-heat conversion efficiency. Under the irradiation of near-infrared light, light can be converted into heat. The inorganic hybrid shell is a drug reservoir. The excellent photothermal response of gold nanorods combined with the excellent pH response of hydroxyapatite can obtain slow and sustained release of chemotherapeutic drugs. In vivo and in vitro anti-tumor cell activity study show that the DNPs in the laser showed stronger cytotoxicity than the other groups. Compared to chemotherapy and phototherapy alone, DNPs selectively accumulate in the tumor through the enhanced penetration and retention (EPR) effects. and have the unified function of hyperthermia and chemotherapy, and have significant inhibitory effect on tumor growth. Therefore, this study provides a new idea for the study of the combination of multiple therapeutic methods in the treatment of cancer.     

载血卟啉单甲醚中空金纳米球的光热光动力联合抗肿瘤研究

目的 设计基于中空金纳米球的新型纳米给药系统(HMME-PEI-HAuNS),在近红外光照射下研究其同步光热光动力联合抗肿瘤作用。方法 以钴纳米粒为模板制备中空金纳米球(HAuNS),将血卟啉单甲醚(HMME)通过枝状聚乙烯亚胺(PEI)装载到HAuNS表面,形成纳米给药系统(HMME-PEI-HAuNS);采用核磁共振氢谱、红外光谱、紫外光谱分析对HMME-PEI-HAuNS进行结构确证。建立荷瘤(SKOV3)小鼠模型,通过荧光活体成像仪考察其体内分布情况。将对肿瘤细胞表面EphB4受体具有特异性亲和力的靶向多肽TNYL修饰于其表面以增强该纳米体系的靶向性,用核染试剂Hoechst染色SKOV3细胞,在激光共聚焦显微镜下观察细胞内的荧光强度,用MTT比色法进行细胞毒性评价。结果 HAuNS能对HMME进行成功装载,装载率达63.4±5.2%。由于肿瘤的高通透性和滞留效应(EPR 效应),HMME-PEI-HAuNS较游离HMME和HMME-PEI胶束在肿瘤部位有更多的累积量和更长的滞留时间,累计效率约为1.6%。荧光定量统计显示在TNYL多肽的介导下纳米球的靶向性更高,在808 nm激光照射下,TNYL-HMME-PEI-HAuNS发挥光热和光动力协同作用产生强大的肿瘤杀伤作用,在高浓度时,细胞存活率不到10%。结论 主动靶向纳米球(TNYL-HMME-PEI-HAuNS)在808 nm近红外光照射下具有较强的光热光动力联合抗肿瘤作用。     

Enhancing of plasmonic photothermal therapy through heat-inducible transgene activity

We explore the synergistic effect of photothermal therapy and gene therapy, simultaneously triggered by silica-gold nanoshells (NS) or hollow gold nanoparticles (HGNPs) in human HeLa cells following near-infrared (NIR) light irradiation. Thermal transfer from NS was higher than that displayed by HGNPs, owing to a differential interaction of the nanomaterial with the biological environment. Under sublethal photothermal conditions, NS and HGNPs effectively modulated the expression levels of a DsRed-monomer reporter gene controlled by the highly heat-inducible human HSP70B promoter, as a function of nanomaterial concentration and length of laser exposure. Hyperthermia treatments at doses that do not promote cell death generated a lethal outcome in HeLa cells harboring the fusogenic GALV-FMG transgene under the control of the HSP70B promoter. Combination of lethal photothermia with the triggering of the cytotoxic transgene resulted in a dramatic increase of the cell-ablation area as a result of the synergistic activity established.From the Clinical EditorIn this study photothermal therapy and gene therapy, simultaneously triggered by silica-gold nanoshells or hollow gold nanoparticles, was investigated in human HeLa cells following near-infrared (NIR) light irradiation. It is shown that the combination of lethal photothermia with the triggering of the cytotoxic transgene at sublethal levels results in a synergistic cytotoxic effect in vitro.     

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.     

Laser immunotherapy with gold nanorods causes selective killing of tumour cells

Therapeutic approaches that exploit nanoparticles to deliver drugs selectively to cancer cells are currently considered one of the most promising avenues in the area of cancer therapeutics. Recently, gold nanorods (AuNRs) have shown promising biological applications due to their unique electronic and optical properties. In this paper, we have demonstrated the anti-cancer potential of gold nanorods with low power laser light. Gold nanorods (AuNRs), surface modified with poly (styrene sulfonate) PSS and functionalized with epidermal growth factor receptor antibody conjugated with gold nanorods (anti-EGFR-AuNRs) were successfully synthesised and characterized by UV-Visible-NIR spectrophotometry and High Resolution Transmission Electron Microscopy (HR-TEM). Inductively Coupled Plasmon Atomic Emission Spectrometry (ICP-AES) and Immunofluorescence studies confirmed the efficient uptake of these functionalized gold nanorods by human squamous carcinoma cells, A431. The in vitro photothermal therapy was conducted in four groups - control, laser alone, unconjugated AuNRs with laser and anti-EGFR conjugated AuNRs with laser. Phase contrast images have revealed cell morphology changes and cell death after the laser irradiation. In order to determine whether the cell death occur due to apoptosis or necrosis, we have evaluated the biochemical parameters such as lactate dehydrogenase release, reactive oxygen species level, mitochondrial membrane potential and caspase-3 activity. Flow cytometry analysis have shown the cell cycle changes after laser irradiation with antibody conjugated gold nanorods. Thus the results of our experiments confirmed that immunolabeled gold nanorods can selectively destruct the cancer cells and induce its apoptosis through ROS mediated mitochondrial pathway under low power laser exposure.     

Tailored core‒shell dual metal–organic frameworks as a versatile nanomotor for effective synergistic antitumor therapy

Malignant tumor has become an urgent threat to global public healthcare. Because of the heterogeneity of tumor, single therapy presents great limitations while synergistic therapy is arousing much attention, which shows desperate need of intelligent carrier for co-delivery. A core‒shell dual metal–organic frameworks (MOFs) system was delicately designed in this study, which not only possessed the unique properties of both materials, but also provided two individual specific functional zones for co-drug delivery. Photosensitizer indocyanine green (ICG) and chemotherapeutic agent doxorubicin (DOX) were stepwisely encapsulated into the nanopores of MIL-88 core and ZIF-8 shell to construct a synergistic photothermal/photodynamic/chemotherapy nanoplatform. Except for efficient drug delivery, the MIL-88 could be functioned as a nanomotor to convert the excessive hydrogen peroxide at tumor microenvironment into adequate oxygen for photodynamic therapy. The DOX release from MIL-88-ICG@ZIF-8-DOX nanoparticles was triggered at tumor acidic microenvironment and further accelerated by near-infrared (NIR) light irradiation. The in vivo antitumor study showed superior synergistic antitumor effect by concentrating the nanoparticles into dissolving microneedles as compared to intravenous and intratumoral injection of nanoparticles, with a significantly higher inhibition rate. It is anticipated that the multi-model synergistic system based on dual-MOFs was promising for further biomedical application.     

Targeting gold nanocages to cancer cells for photothermal destruction and drug delivery

Importance of the field: Plasmonic nanoparticles provide a new route to treat cancer owing to their ability to convert light into heat effectively for photothermal destruction. Combined with the targeting mechanisms possible with nanoscale materials, this technique has the potential to enable highly targeted therapies to minimize undesirable side effects.

Areas covered in this review: This review discusses the use of gold nanocages, a new class of plasmonic nanoparticles, for photothermal applications. Gold nanocages are hollow, porous structures with compact sizes and precisely controlled plasmonic properties and surface chemistry. Also, a recent study of gold nanocages as drug-release carriers by externally controlling the opening and closing of the pores with a smart polymer whose conformation changes at a specific temperature is discussed. Release of the contents can be initiated remotely through near-infrared irradiation. Together, these topics cover the years from 2002 to 2009.

What the reader will gain: The reader will be exposed to different aspects of gold nanocages, including synthesis, surface modification, in vitro studies, intial in vivo data and perspectives on future studies.

Take home message: Gold nanocages are a promising platform for cancer therapy in terms of both photothermal destruction and drug delivery.     

Gold nanorods: their potential for photothermal therapeutics and drug delivery, tempered by the complexity of their biological interactions

Gold nanorods have promising applications in the fields of drug delivery and photothermal therapy. These promises arise from the nanorods' unique optical and photothermal properties, the availability of synthetic protocols that can tune the size and shape of the particles, the ability to modify the surface and conjugate drugs/molecules to the nanorods, and the relative biocompatibility of gold nanorods. In this review, current progress in using gold nanorods as phototherapeutic agents and as drug delivery vehicles is summarized. Issues of dosage, toxicity and biological interactions at three levels (biological media alone; cells; whole organisms) are discussed, concluding with recommendations for future work in this area.     

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.     

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.     

NIR-triggered thermo-responsive biodegradable hydrogel with combination of photothermal and thermodynamic therapy for hypoxic tumor

Hypoxia is a typical feature of solid tumors, which highly limits the application of the oxygen-dependent therapy. Also, the dense and hyperbaric tumor tissues impede the penetration of nanoparticles into the deep tumor. Thereby, we designed a novel localized injectable hydrogel combining the photothermal therapy (PTT) and the thermodynamic therapy (TDT), which is based on the generation of free radicals even in the absence of oxygen for hypoxic tumor therapy. In our study, gold nanorods (AuNRs) and 2,2′-Azobis[2-(2-imidazalin-2-yl)propane] dihydrochlaride (AIPH) were incorporated into the hydrogel networks, which were formed by the copolymerization of hydrophobic N-isopropyl acrylamide (NIPAM) and hydrophilic glycidyl methacrylate modified hyaluronic acid (HA-GMA) to fabricate an injectable and near-infrared (NIR) responsive hydrogel. The crosslinked in situ forming hydrogel could not only realize PTT upon the NIR laser irradiation, but also generate free radicals even in hypoxic condition. Meanwhile the shrink of hydrogels upon thermal could accelerate the generation of free radicals to further damage the tumors, achieving the controlled drug release on demand. The designed hydrogel with a sufficient loading capacity, excellent biocompatibility and negligible systemic toxicity could serve as a long-acting implant for NIR-triggered thermo-responsive free radical generation. The in vitro cytotoxicity result and the in vivo antitumor activity illustrated the excellent therapeutic effect of hydrogels even in the absence of oxygen. Therefore, this innovative oxygen-independent platform combining the antitumor effects of PTT and TDT would bring a new insight into hypoxic tumor therapy by the application of alkyl free radical.     

Development of a novel thermal-sensitive multifunctional liposome with antibody conjugation to target EGFR-expressing tumors

A novel EGFR-targeting, thermal-sensitive multifunctional liposome (TSML) was developed based on manganese-doped magnetism-engineered iron oxide nanoparticles (MnMEIOs) and gold nanorods (AuNRs) for efficient photothermal therapy and magnetic resonance (MR) imaging. An Erbitux-conjugated TSML (Erb-TSML) was encapsulated with doxorubicin and gold nanorods conjugated with manganese-doped magnetism-engineered iron oxide nanoparticles, for theranostic applications of EGFR-positive tumors. The Erb-TSML selectively targeted EGFR-positive tumors and promoted tumor destruction by laser activation. Using confocal microscopy, MR and optical imaging, we demonstrated that Erb-TSML specifically bound to A431 tumor cells. No signs of major morphological damages to the normal tissues were observed in mice treated with Erb-TSML and laser, indicating this theranostic platform protected heart against doxorubicin-induced toxicity to normal tissues. These results indicate that the Erb-TSML may be a promising diagnostic and therapeutic platform for EGFR-overexpressing tumors.     

Influence of chitosan coating on the oral bioavailability of gold nanoparticles in rats

Gold nanoparticles are one of the most extensively investigated metallic nanoparticles for several applications. It is less toxic than other metallic nanolattices. The exceptional electrical and thermal conductivity of gold make it possible to be administered as non-invasive radiofrequency irradiation therapy that produces sufficient heat to kill tumor cells. Nanoparticles are generally administered intravenously instead of orally due to negligible oral absorption and cellular uptake. This study evaluated the oral bioavailability of gold nanoparticles coated with chitosan (C-AuNPs), a natural mucoadhesive polymer. We employed traditional method of evaluating bioavailability that involve estimation of maximum concentrations and area under the curve of 3?nm chitosan coated gold nanoparticles (C-AuNPs) in the rat plasma following intravenous and oral administrations (0.8?mg and 8?mg/kg body weight respectively). The oral bioavailability of C-AuNPs was found to be 2.46% (approximately 25 folds higher than polyethylene glycol (PEG) coated gold nanoparticles, reported earlier). These findings suggest that chitosan coating could be better than PEG coating for the enhancement of oral bioavailability of nanoparticles.     

Cell Mediated Photothermal Therapy of Brain Tumors

Gold based nanoparticles with strong near infra-red (NIR) absorption are ideally suited for photothermal therapy (PTT) of brain tumors. The goal of PTT is to induce rapid heating in tumor tissues while minimizing thermal diffusion to normal brain. PTT efficacy is sensitively dependent on both nanoparticle concentration and distribution in tumor tissues. Nanoparticle delivery via passive approaches such as the enhanced permeability and retention (EPR) effect is unlikely to achieve sufficient nanoparticle concentrations throughout tumor volumes required for effective PTT. A simple approach for improving tumor biodsitribution of nanoparticles is the use of cellular delivery vehicles. Specifically, this review focuses on the use of monocytes/macrophages (Mo/Ma) as gold nanoparticle delivery vectors for PTT of brain tumors. Although the efficacy of this delivery approach has been demonstrated in both in vitro and animal PTT studies, its clinical potential for the treatment of brain tumors remains uncertain.     

壳聚糖递送系统在肿瘤光热治疗中的应用和进展

肿瘤持续侵袭着人类健康,光热治疗作为一种肿瘤治疗的新方法受到越来越多的关注和研究。壳聚糖是一种天然来源丰富的阳离子多糖,具有良好的生物相容性、可降解性、结构衍生化特性。壳聚糖及其衍生物的骨架上含有大量的氨基和羟基,可通过物理或者化学方法形成壳聚糖纳米粒、水凝胶以及涂层等多种形式的载体,装载或结合光热转换剂,在近红外激光辐射下形成局部高温抑制肿瘤细胞。本综述系统介绍了壳聚糖递送系统在肿瘤光热治疗方面的研究进展。     

Polydopamine-coated i-motif DNA/Gold nanoplatforms for synergistic photothermal-chemotherapy

The combination of photothermal therapy with chemotherapy has gradually developed into promising cancer therapy. Here, a synergistic photothermal-chemotherapy nanoplatform based on polydopamine (PDA)-coated gold nanoparticles (AuNPs) were facilely achieved via the in situ polymerization of dopamine (DA) on the surface of AuNPs. This nanoplatform exhibited augmented photothermal conversion efficiency and enhanced colloidal stability in comparison with uncoated PDA shell AuNPs. The i-motif DNA nanostructure was assembled on PDA-coated AuNPs, which could be transformed into a C-quadruplex structure under an acidic environment, showing a characteristic pH response. The PDA shell served as a linker between the AuNPs and the i-motif DNA nanostructure. To enhance the specific cellular uptake, the AS1411 aptamer was introduced to the DNA nanostructure employed as a targeting ligand. In addition, Dox-loaded NPs (DAu@PDA-AS141) showed the pH/photothermal-responsive release of Dox. The photothermal effect of DAu@PDA-AS141 elicited excellent photothermal performance and efficient cancer cell inhibition under 808 nm near-infrared (NIR) irradiation. Overall, these results demonstrate that the DAu@PDA-AS141 nanoplatform shows great potential in synergistic photothermal-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.