Targetable gold nanorods for epithelial cancer therapy guided by near-IR absorption imaging

Well-designed nanoparticle-mediated, image-guided cancer therapy has attracted interest for increasing the efficacy of cancer treatment. A new class of smart theragnostic nanoprobes employing cetuximab (CET)-conjugated polyethylene glycol (PEG)ylated gold nanorods (CET-PGNRs) is presented; these nanoprobes target epithelial cancer cells using near-infrared light. The cetyltrimethylammonium bromide bilayer on GNRs is replaced with heterobifunctional PEG (COOH-PEG-SH) to serve as a biocompatible stabilizer and to increase specificity. The carboxylated GNRs are further functionalized with CET using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC-NHS) chemistry. To assess the potential of such GNRs, their optical properties, biocompatibility, colloidal stability, in vitro/in vivo binding affinities for cancer cells, absorption imaging, and photothermal therapy effects are investigated. CET-PGNRs exhibit excellent tumor targeting ability and strong potential for simultaneous absorption imaging and photothermal ablation of epithelial cancer cells.     

Enhanced Photothermal Therapy through the In Situ Activation of a Temperature and Redox Dual‐Sensitive Nanoreservoir of Triptolide

Photothermal therapy (PTT) has attracted tremendous attention due to its noninvasiveness and localized treatment advantages. However, heat shock proteins (HSPs) associated self‐preservation mechanisms bestow cancer cells thermoresistance to protect them from the damage of PTT. To minimize the thermoresistance of cancer cells and improve the efficacy of PTT, an integrated on‐demand nanoplatform composed of a photothermal conversion core (gold nanorod, GNR), a cargo of a HSPs inhibitor (triptolide, TPL), a mesoporous silica based nanoreservoir, and a photothermal and redox di‐responsive polymer shell is developed. The nanoplatform can be enriched in the tumor site, and internalized into cancer cells, releasing the encapsulated TPL under the trigger of intracellular elevated glutathione and near‐infrared laser irradiation. Ultimately, the liberated TPL could diminish thermoresistance of cancer cells by antagonizing the PTT induced heat shock response via multiple mechanisms to maximize the PTT effect for cancer treatment.     

Assessing the effect of surface chemistry on gold nanorod uptake, toxicity, and gene expression in mammalian cells

Through the use of various layer-by-layer polyelectrolyte (PE) coating schemes, such as the common poly(diallyldimethylammonium chloride)-poly(4-styrenesulfonic acid) (PDADMAC-PSS) system, the mammalian cellular uptake of gold nanorods can be tuned from very high to very low by manipulating the surface charge and functional groups of the PEs. The toxicity of these nanorods is also examined. Since the PE coatings are individually toxic, the toxicity of nanorods coated in these PEs is measured and cells are found to be greater than 90% viable in nearly all cases, even at very high concentrations. This viability assay may not be a complete indicator of toxicity, and thus gene-expression analysis is used to examine the molecular changes of cells exposed to PDADMAC-coated nanorods, which enter cells at the highest concentrations. Indicators of cell stress, such as heat-shock proteins, are not significantly up- or down-regulated following nanorod uptake, which suggests that PDADMAC-coated gold nanorods have negligible impact on cell function. Furthermore, a very low number of genes experience any significant change in expression (0.35% of genes examined). These results indicate that gold nanorods are well suited for therapeutic applications, such as thermal cancer therapy, due to their tunable cell uptake and low toxicity.     

<Emphasis Type="Italic">In situ</Emphasis> synthesis of graphene oxide/gold nanorods theranostic hybrids for efficient tumor computed tomography imaging and photothermal therapy

Graphene oxide/gold nanorod (GO/GNR) nanohybrids were synthesized with a GO- and gold-seed-mediated in situ growth method at room temperature by mixing polystyrene sulfonate (PSS) functionalized GO, secondary growth solution, and gold seeds. Compared with ex situ preparation methods of GO/GNRs or graphene (G)/GNRs, the in situ synthesis of GO/GNRs addressed the issue of the aggregation of the GNRs before their attachment onto the GO. The method is straightforward and environment-friendly. The GO/GNRs showed a remarkable photothermal effect in vitro. The temperature of the GO/GNR nanohybrids increased from 25 to 49.9 °C at a concentration of 50 μg/mL after irradiation with an 808-nm laser (0.4 W/cm²) for 6 min. Additionally, the GO/GNRs exhibited good optical and morphological stability and photothermal properties after six cycles of laser irradiation. Upon injection of the GO/GNRs into xenograft tumors, excellent computed tomography (CT) imaging properties and photothermal effect were obtained. The preclinical CT agent iohexol was combined with the GO/GNRs and further enhanced CT imaging. Therefore, the GO/GNR nanohybrids have great potential for precise CT-image-guided tumor photothermal treatment.

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First Demonstration of Gold Nanorods‐Mediated Photodynamic Therapeutic Destruction of Tumors via Near Infra‐Red Light Activation

Previously, a large volume of papers reports that gold nanorods (Au NRs) are able to effectively kill cancer cells upon high laser doses (usually 808 nm, 1–48 W/cm²) irradiation, leading to hyperthermia‐induced destruction of cancer cells, i.e, photothermal therapy (PTT) effects. Combination of Au NRs‐mediated PTT and organic photosensitizers‐mediated photodynamic therapy (PDT) were also reported to achieve synergistic PTT and PDT effects on killing cancer cells. Herein, we demonstrate for the first time that Au NRs alone can sensitize formation of singlet oxygen (¹O₂) and exert dramatic PDT effects on complete destrcution of tumors in mice under very low LED/laser doses of single photon NIR (915 nm, <130 mW/cm²) light excitation. By changing the NIR light excitation wavelengths, Au NRs‐mediated phototherapeutic effects can be switched from PDT to PTT or combination of both. Both PDT and PTT effects were confirmed by measurements of reactive oxygen species (ROS) and heat shock protein (HSP 70), singlet oxygen sensor green (SOSG) sensing, and sodium azide quenching in cellular experiments. In vivo mice experiments further show that the PDT effect via irradiation of Au NRs by 915 nm can destruct the B16F0 melanoma tumor in mice far more effectively than doxorubicin (a clinically used anti‐cancer drug) as well as the PTT effect (via irradiation of Au NRs by 780 nm light). In addition, we show that Au NRs can emit single photon‐induced fluorescence to illustrate their in vivo locations/distribution.     

Hydrophilic bismuth sulfur nanoflower superstructures with an improved photothermal efficiency for ablation of cancer cells

Nanomaterials with intense near-infrared (NIR) absorption exhibit effective photon-to-thermal energy transfer capabilities and can generate heat to ablate cancer cells, thus playing a pivotal role in photothermal cancer therapeutics. Herein, hydrophilic flower-like bismuth sulfur (Bi₂S₃) superstructures with uniform size and improved NIR absorption were controllably synthesized via a facile solvothermal procedure assisted by polyvinylpyrrolidone (PVP), which could adjust the product morphology. Induced by an 808-nm laser, the as-prepared Bi₂S₃ nanoflowers exhibited much higher photothermal conversion efficiency (64.3%) than that of Bi₂S₃ nanobelts (36.5%) prepared in the absence of PVP. This can be attributed not only to the Bi₂S₃ nanoflower superstructures assembled by 3-dimensional crumpled-paper-like nanosheets serving as many laser-cavity mirrors with improved reflectivity and absorption of NIR light but also to the amorphous structures with a lower band gap. Thus, to achieve the same temperature increase, the concentration or laser power density could be greatly reduced when using Bi₂S₃ nanoflowers compared to when using Bi₂S₃ nanobelts, which makes them more favorable for use in therapy due to decreased toxicity. Furthermore, these Bi₂S₃ nanoflowers effectively achieved photothermal ablation of cancer cells in vitro and in vivo. These results not only supported the Bi₂S₃ nanoflowers as a promising photothermal agent for cancer therapy but also paved an approach to exploit new agents with improved photothermal efficiency.

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无捕收剂浮选提高金矿回收率试验研究

为建设环保矿山并提高金矿回峰率,进行了无捕收剂浮选的试验研究。对磨矿细度、调整剂用量、硫化钠用量、起泡剂用量等条件进行了研究。结果表明,采用无捕收剂浮选工艺,在原矿金品位16．75g／t,磨矿细度细度-0．074mm占60％、硫化钠用量600克／吨,2#油用量234．8g／t、浮选时间24min的情况下,可获得金精矿平均品位45．96g／t、回收率96．33％的技术指标。比选矿厂原生产指标（92％左右）提高了4％以上的回收率。     

The effect of size and shape of gold nanoparticles on thin film properties

This work describes the properties of gold nanoparticles (AuNPs) thin film on silicon (Si) substrates. The AuNPs can be divided into two major shapes: gold nanospheres (AuNSs) and gold nanorods (AuNRs). Two sizes of AuNSs (15 nm and 30 nm) and three aspect ratios of AuNRs (3.12, 3.39 and 3.60) were synthesised using the seeding-growth method. The AuNPs produced were deposited on Si substrates by using a spin-coating method followed by heat treatment at 200 °C. The number of AuNPs coatings varied as one, three and five coating depositions, respectively. From the field emission scanning electron microscopy, the AuNPs were uniformly distributed on the Si substrate surface. The AuNPs distribution increased with increasing number of AuNPs coating. Various deposited AuNPs with different shapes and sizes were analysed using current–voltage (I–V) measurement in light–dark conditions. The results showed that the resistance of samples became lower under light condition as the number of AuNPs coatings increased on the Si substrate due to the large amount of AuNPs particles, which had better properties in absorbing and scattering the light intensity. Among these samples, five-coating depositions of 15 nm AuNSs and 3.12 aspect ratio of AuNRs thin films gave the best sensitivity in light–dark condition. The higher sensitivity implied the better sensing and recovery properties since it can amplify a small signal from the same light source power/intensity.     

Chemo/Photoacoustic Dual Therapy with mRNA‐Triggered DOX Release and Photoinduced Shockwave Based on a DNA‐Gold Nanoplatform

A multifunctional nanoparticle based on gold nanorod (GNR), utilizing mRNA triggered chemo‐drug release and near‐infrared photoacoustic effect, is developed for a combined chemo‐photoacoustic therapy. The constructed nanoparticle (GNR‐DNA/FA:DOX) comprises three functional components: (i) GNR as the drug delivery platform and photoacoustic effect enhancer; (ii) toehold‐possessed DNA dressed on the GNR to load doxorubicin (DOX) to implement a tumor cell specific chemotherapy; and (iii) folate acid (FA) modified on GNR to guide the nanoparticle to target tumor cells. The results show that, upon an effective and specific delivery of the nanoparticles to the tumor cells with overexpressed folate receptors, the cytotoxic DOX loaded on the GNR‐DNA nanoplatform can be released through DNA displacement reaction in melanoma‐associated antigen gene mRNA expressed cells. With 808 nm pulse laser irradiation, the photoacoustic effect of the GNR leads to a direct physical damage to the cells. The combined treatment of the two modalities can effectively destroy tumor cells and eradicate the tumors with two distinctively different and supplementing mechanisms. With the nanoparticle, photoacoustic imaging is successfully performed in situ to monitor the drug distribution and tumor morphology for therapeutical guidance. With further in‐depth investigation, the proposed nanoparticle may provide an effective and safe alternative cancer treatment modality.     

In situ organization of gold nanorods on mixed self-assembled-monolayer substrates

A method is described for assembling gold nanorods, end-to-end, into long chains attached on top of a mixed self-assembled monolayer that has been functionalized with streptavidin. Methods to prepare chains of nanorods in colloidal suspension have been reported by others, but our protocol offers a way to directly form such structures on a substrate. The rods are spaced approximately 5 nm apart in the resulting chains, which extend for over a micrometer in length. The assembly and morphology of the nanorod structures were characterized by surface plasmon resonance spectroscopy, as well as by scanning electron microscopy and scanning probe microscopy. Structures of this type could conceivably serve as plasmonic waveguides in future nanodevices.     

A Comparative Study of Clinical Intervention and Interventional Photothermal Therapy for Pancreatic Cancer

Although nanoparticle‐based photothermal therapy (PTT) has been intensively investigated recently, its comparative efficiency with any clinical cancer treatments has been rarely explored. Herein for the first time we report a systematic comparative study of clinical iodine‐125 (¹²⁵I) interstitial brachytherapy (IBT‐125‐I) and interventional PTT (IPTT) in an orthotopic xenograft model of human pancreatic cancer. IPTT, based on the nanoparticles composing of anti‐urokinase plasminogen activator receptor (uPAR) antibody, polyethylene glycol (PEG), and indocyanine green (ICG) modified gold nanoshells (hereinafter uIGNs), is directly applied to local pancreatic tumor deep in the abdomen. In comparison to IBT‐125‐I, a 25% higher median survival rate of IPTT with complete ablation by one‐time intervention has been achieved. The IPTT could also inhibit pancreatic tumor metastasis which can be harnessed for effective cancer immunotherapy. All results show that this IPTT is a safe and radical treatment for eradicating tumor cells, and may benefit future clinical pancreatic cancer patients.     

Superparamagnetic Gold Nanoparticles Synthesized on Protein Particle Scaffolds for Cancer Theragnosis

Cancer theragnosis using a single multimodality agent is the next mainstay of modern cancer diagnosis, treatment, and management, but a clinically feasible agent with in vivo cancer targeting and theragnostic efficacy has not yet been developed. A new type of cancer theragnostic agent is reported, based on gold magnetism that is induced on a cancer‐targeting protein particle carrier. Superparamagnetic gold‐nanoparticle clusters (named SPAuNCs) are synthesized on a viral capsid particle that is engineered to present peptide ligands targeting a tumor cell receptor (TCR). The potent multimodality of the SPAuNCs is observed, which enables TCR‐specific targeting, T₂‐weighted magnetic resonance imaging, and magnetic hyperthermia therapy of both subcutaneous and deep‐tissue tumors in live mice under an alternating magnetic field. Furthermore, it is analytically elucidated how the magnetism of the SPAuNCs is sufficiently induced between localized and delocalized spins of Au atoms. In particular, the SPAuNCs show excellent biocompatibility without the problem of in vivo accumulation and holds promising potential as a clinically effective agent for cancer theragnosis.     

Effect of ZnO seed layer on the catalytic growth of vertically aligned ZnO nanorod arrays

We have grown vertically aligned ZnO nanorods and multipods by a seeded layer assisted vapor–liquid–solid (VLS) growth process using a muffle furnace. The effect of seed layer, substrate temperature and substrate material has been studied systematically for the growth of high quality aligned nanorods. The structural analysis on the aligned nanorods shows c-axis oriented aligned growth by homoepitaxy. High crystallinity and highly aligned ZnO nanorods are obtained for growth temperature of 850–900 °C. Depending on the thickness of the ZnO seed layer and local temperature on the substrate, some region of a substrate show ZnO tetrapod, hexapods and multipods, in addition to the vertically aligned nanorods. Raman scattering studies on the aligned nanorods show distinct mode at ∼438 cm⁻¹, confirming the hexagonal wurtzite phase of the nanorods. Room temperature photoluminescence studies show strong near band edge emission at ∼378 nm for aligned nanorods, while the non-aligned nanorods show only defect-emission band at ∼500 nm. ZnO nanorods grown without the seed layer were found to be non-aligned and are of much inferior quality. Possible growth mechanism for the seeded layer grown aligned nanorods is discussed.     

Comparative enhancement of curcumin cytotoxic photodynamic activity by nanoliposomes and gold nanoparticles with pharmacological appraisal in HepG2 cancer cells and Erlich solid tumor model

Curcumin is a natural pigment that generates singlet oxygen upon light excitation, hence it can be used as a photosensitizer in photodynamic therapy. The extremely low water solubility and poor systemic bioavailability make curcumin a challenging molecule to be used clinically. In this study, two nanocarrier systems for curcumin were prepared and characterized; nanoliposomes and polyvinyl pyrrolidone-capped gold nanoparticles. The dark and photocytotoxicity were investigated as a function of light fluence rate (100 and 200?mW/cm²) on HepG2 cancer cells. In vivo Erlich tumor model was developed and comparison of the tumor volume, survival rate, and histopathological alterations was made for the two nanocarriers. Results showed that both curcumin nanocarriers were successfully prepared and characterized. Light irradiation was able to augment the cytotoxicity of both curcumin liposomes and gold nanoparticles, with the former being superior in cytotoxicity compared to the latter. The tumor size was almost diminished 1 month post-photodynamic treatment for both systems with regression in the number of tumor cells upon histopathological evaluation, with curcumin liposomes producing better tumor regression than gold nanoparticles with comparable survival rate. Liposomes were confirmed to be superior to gold nanoparticles as a photodynamic treatment modality for cancer.     

Unlocking the Potential of Magnetotactic Bacteria as Magnetic Hyperthermia Agents

Magnetotactic bacteria are aquatic microorganisms that internally biomineralize chains of magnetic nanoparticles (called magnetosomes) and use them as a compass. Here it is shown that magnetotactic bacteria of the strain Magnetospirillum gryphiswaldense present high potential as magnetic hyperthermia agents for cancer treatment. Their heating efficiency or specific absorption rate is determined using both calorimetric and AC magnetometry methods at different magnetic field amplitudes and frequencies. In addition, the effect of the alignment of the bacteria in the direction of the field during the hyperthermia experiments is also investigated. The experimental results demonstrate that the biological structure of the magnetosome chain of magnetotactic bacteria is perfect to enhance the hyperthermia efficiency. Furthermore, fluorescence and electron microscopy images show that these bacteria can be internalized by human lung carcinoma cells A549, and cytotoxicity studies reveal that they do not affect the viability or growth of the cancer cells. A preliminary in vitro hyperthermia study, working on clinical conditions, reveals that cancer cell proliferation is strongly affected by the hyperthermia treatment, making these bacteria promising candidates for biomedical applications.