Agent For Ablation Research Articles

A tumor-targeting near-infrared laser-triggered drug delivery system based on GO@Ag nanoparticles for chemo-photothermal therapy and X-ray imaging

In this study, a GO@Ag nanocomposite was synthesized by chemical deposition of Ag nanoparticles onto graphene oxide (GO) through a hydro thermal reaction, and doxorubicin (DOX), one of the most effective drugs against a wide range of cancers, was employed as the model drug and linked to GO@Ag via ester bonds with a very high drug loading efficiency (∼82.0%, weight ratio of DOX/GO@Ag), then GO@Ag-DOX was functionalized by DSPE-PEG2000-NGR, giving GO@Ag-DOX with active tumor-targeting capacity and excellent stability in physiological solutions. The release profiles of DOX from GO@Ag-DOX-NGR showed strong dependences on near-infrared (NIR) laser and the SPR effect of Ag nanoparticles. Compared with free DOX in an in vivo murine tumor model, GO@Ag-DOX-NGR afforded much higher antitumor efficacy without obvious toxic effects to normal organs owing to 8.4-fold higher DOX uptake of tumor and 1.7-fold higher DOX released in tumor with NIR laser than the other tissues. Besides, in this work, GO@Ag-DOX-NGR not only served as a powerful tumor diagnostic X-ray contrast agent, but also as a strong agent for photothermal ablation of tumor, the ability of GO@Ag-DOX-NGR nanoparticles to combine the local specific chemotherapy with external photothermal therapy (PTT) significantly improved the therapeutic efficacy. GO@Ag-DOX-NGR showed excellent chem-photothermal therapeutic efficacy, tumor-targeting property, NIR laser-controlled drug releasing function and X-ray imaging ability, demonstrating that there is a great potential of GO@Ag-DOX-NGR for cancer diagnosis and therapy.

A fullerene-based multi-functional nanoplatform for cancer theranostic applications

Recently, nanomaterials with multiple functions, such as drug carrier, MRI and optical imaging, photothermal therapy etc, have become more and more popular in the domain of cancer research. In this study, a C60–IONP nanocomposite is synthesized via decorating iron oxide nanoparticles (IONP) onto fullerene (C60) and then functionalized by polyethylene glycol (PEG2000), giving C60–IONP–PEG with excellent stability in physiological solutions, finally folic acid (FA), a widely used tumor targeting molecule, was linked to C60–IONP–PEG in order to obtain an active tumor targeting effect to MCF-7 cells and malignant tumor in mice models. Herein, a hybrid nanoplatform with multi-functional characteristics for cancer diagnosis, photodynamic therapy (PDT), radiofrequency (RF) thermal therapy (RTT) and magnetic targeting applications was developed and explored its biofunctions in vitro and in vivo. C60–IONP–PEG–FA showed neglectable toxicity, not only served as a powerful tumor diagnostic magnetic resonance imaging (MRI) contrast agent, but also as a strong photosensitizer and powerful agent for photothermal ablation of tumor, furthermore a remarkable synergistic enhancement of PDT combination with RTT was also observed during the treatment both in vitro and in vivo. Moreover, the multi-functional nanoplatform also could selectively kill cancer cells in highly localized regions via the excellent active tumor targeting and magnetic targeted abilities. This work showed the multi-functional C60–IONP–PEG–FA nanoplatform had a great potential for cancer theranostic applications.

Role of the 5-HT7 receptor in the effects of intrathecal nefopam in neuropathic pain in rats

Nefopam is a non-opioid analgesic drug, used widely in European countries to control postoperative pain. However, its mechanism of action remains unclear. In this study, the effects of intrathecal nefopam on spinal nerve-ligated induced neuropathic pain in rats were examined and the involvement of the 5-HT7 receptor at the spinal level was determined. Next, a 5-HT7 receptor antagonist (SB-269970) or descending serotonergic pathway ablation agent (5,7-DHT) was administered intrathecally before delivery of the nefopam to determine the contribution of spinal 5-HT7 receptors or descending serotonergic pathway to the activity of nefopam. The concentrations of 5-HT were measured. Intrathecal nefopam dose-dependently produced the antiallodynic effect. Pre-treatment with intrathecal SB-269970 reversed the antiallodynic effect of the nefopam. 5,7-DHT failed to affect the effect of nefopam. The concentrations of 5-HT in the spinal cord and plasma were decreased in neuropathic pain. Intrathecal nefopam increased the levels of 5-HT in the spinal cord and plasma. Intrathecal nefopam is effective in the attenuation of neuropathic pain induced by spinal nerve ligation and nefopam increases the level of 5-HT. Additionally, the 5-HT7 receptor is involved in the antiallodynic action of nefopam in the spinal cord.

A Nanoengineered Embolic Agent for Precise Radiofrequency Ablation

The purpose of the work is to investigate whether the electromagnetic properties of multi-walled carbon nanotubes (MWCNT) in the presence of radiofrequency (RF) energy is (1) safe, and (2) improves the precision of the therapeutic efficiency of the RF-ablation (RFA) procedure. An in vitro phantom was created for evaluating temperature near RF treated nanotubes. For the in vivo study, three baboons and six pigs were submitted for RFA procedure in superior/inferior kidney poles embolized with a non-adherent, lipophilic embolic agent (marsembol) with or without MWCNT. Tissue damage in the surrounding kill zone was assayed through caspase-3 activation. The in vitro results showed marked heat increase only in the region of the nanotubes. In vivo, necrosis/ischemic damage resulted from RFA therapy alone, RFA plus marsembol only. In marsembol+MWCNT condition, dramatic disruption of cell membranes and sub-cellular organelles was found whereas the nuclear membranes and basal cell membranes remained largely intact. The marsembol vaporized under RFA and tissue fluid filled the space. This caused the MWCNT to cluster within the new aqueous environment. RFA plus marsembol+MWCNT created a well-defined demarcation between healthy and apoptotic cells as evidenced by a marked reduction of caspase-3 expression. By contrast, there was a much less defined ablation zone in the absence of MWCNT. In conclusion, the combination of RFA plus marsembol+MWCNT embolization delineated the kill zone in vitro and in vivo. We demonstrate that MWCNTs remain in the ablation region thus minimizing their migration to the systemic circulation.

Establishing a rat model of spastic cerebral palsy by targeted ethanol injection.

Spastic cerebral palsy is generally considered to result from cerebral cortical or pyramidal tract damage. Here, we precisely targeted the left pyramidal tract of 2-month-old Sprague-Dawley rats placed on a stereotaxic instrument under intraperitoneal anesthesia. Based on the rat brain stereotaxic map, a 1-mm hole was made 10 mm posterior to bregma and 0.8 mm left of sagittal suture. A microsyringe was inserted perpendicularly to the surface of the brain to a depth of 9.7 mm, and 15 μL of ethanol was slowly injected to establish a rat model of spastic cerebral palsy. After modeling, the rats appeared to have necrotic voids in the pyramidal tract and exhibited typical signs and symptoms of flexion spasms that lasted for a long period of time. These findings indicate that this is an effective and easy method of establishing a rat model of spastic cerebral palsy with good re-producibility. Ethanol as a chemical ablation agent specifically and thoroughly damages the pyramidal tract, and therefore, the animals display flexion spasms, which are a typical symptom of the disease.

Formulation of curcumin delivery with functionalized single-walled carbon nanotubes: characteristics and anticancer effects in vitro

Context: Single-walled carbon nanotubes (SWCNTs), an important class of artificial nanomaterials with unique physicochemical properties, were used as novel carriers of curcumin.Objective: Formulation and evaluation of curcumin-loaded SWCNTs systems for utilizing the curcumin’s anticancer potential by circumventing conventional limitations of extremely low aqueous solubility and instability under physiological conditions, and combining SWCNTs photothermal therapy enabled by the strong optical absorbance of SWCNTs in the 0.8–1.4 μm resulting in excessive local heating.Methods: After functionalized SWCNTs were confirmed, they were conjugated with curcumin (SWCNT-Cur). Subsequently, the formulation was analyzed for size, zeta-potential and morphology. And the solubility, stability and release of curcumin were assessed using spectrofluorometer, and the solid state of the curcumin was determined using X-ray diffraction and UV spectroscopy. Furthermore, in PC-3 cells, photothermal response was further determined by irradiating laser after the antitumor effect of SWCNT-Cur was evaluated.Results and discussion: SWCNTs were functionalized, and subsequent SWCNT-Cur conjugates were found to possess an average size of 170.4 nm, a zeta potential of −12.5 mV and to significantly enhance the solubility and stability of curcumin, overcoming the barriers to adequate curcumin delivery. Moreover, curcumin in SWCNT-Cur was in an amorphous form and could be rapidly released. In PC-3 cells, improved inhibition efficacy was achieved by SWCNT-Cur compared with native curcumin. Meanwhile, the SWCNTs in SWCNT-Cur served not only as scaffolds but also as thermal ablation agents, further inhibiting PC-3 cell growth.Conclusion: SWCNT-Cur assemblies may provide a promising delivery system for curcumin for use in cancer therapy.

Engineering of perfluorooctylbromide polypyrrole nano-/microcapsules for simultaneous contrast enhanced ultrasound imaging and photothermal treatment of cancer

A versatile oil-in-water emulsion method has been explored for constructing water-dispersible polypyrrole (PPy) nano-/microcapsules with a soluble PPy complex as multifunctional photothermal agents for tumor ablation. In this work, both PPy nanocapsules (280.4 ± 79.0 nm) and microcapsules (1.31 ± 0.45 μm) with liquid perfluorooctylbromide (PFOB) core could be obtained by simply tuning the process energy for emulsion formation from ultrasonication to homogenization. Owing to the encapsulated liquid PFOB and strong near-infrared (NIR) absorption of PPy shell, the resulted PPy capsules showed great promise in ultrasound imaging guided photothermal ablation of tumor cells without inducing any significant side effect. Thus, it is anticipated that fine-tuning of the other encapsulated drugs or functional materials in PPy capsules would foster avenues for the development of multifunctional platforms for cancer treatments.

PEGylated Micelle Nanoparticles Encapsulating a Non‐Fluorescent Near‐Infrared Organic Dye as a Safe and Highly‐Effective Photothermal Agent for In Vivo Cancer Therapy

AbstractPhotothermal therapy (PTT), as a minimally invasive and highly effective cancer treatment approach, has received widespread attention in recent years. Tremendous effort has been devoted to explore various types of photothermal agents with high near‐infrared (NIR) absorbance for PTT cancer treatment. Despite many exciting progresses in the area, effective yet safe photothermal agents with good biocompatibility and biodegradability are still highly desired. In this work, a new organic PTT agent based on polyethylene glycol (PEG) coated micelle nanoparticles encapsulating a heptamethine indocyanine dye IR825 is developed, showing a strong NIR absorption band and a rather low quantum yield, for in vivo photothermal treatment of cancer. It is found that the IR825–PEG nanoparticles show ultra‐high in vivo tumor uptake after intravenous injection, and appear to be an excellent PTT agent for tumor ablation under a low‐power laser irradiation, without rendering any appreciable toxicity to the treated animals. Compared with inorganic nanomaterials and conjugated polymers being explored in PTT, the NIR‐absorbing micelle nanoparticles presented here may have the least safety concern while showing excellent treatment efficacy, and thus may be a new photothermal agent potentially useful in clinical applications.

Evaluation of a Silver Nitrate Endometrial Ablation Fluid Delivery System as a Chemical Treatment for Menorrhagia

Study ObjectiveTo explore the safety, feasibility, and effectiveness of silver nitrate–dextran paste delivered through the cervix as a simple and inexpensive endometrial ablation therapy for menorrhagia. DesignSafety, feasibility, and effectiveness trials (Canadian Task Force classification II-3). SettingThe trials were performed at the Whittington Hospital in London. PatientsSeven women were treated for menorrhagia after prehysterectomy trials on 10 patients. Studies were first performed on rats and rabbits and human uterine specimens. InterventionWe dissolved 10 g 75% silver nitrate/25% potassium nitrate and 15 g dextran 70 in 10 mL distilled water and delivered this paste through the cervix with a pressure-controlled syringe under fluroscopic monitoring. We planned silver nitrate doses of 500 mg in a 50-kg woman to remain in the uterus for 8 minutes after injection and then to be neutralized with normal saline and washed out. In uterine specimens, 8-minute treatment produced local necrosis to 4 mm. LD50 (lethal dose, 50%) studies in rats and mice ranged from 1100 to 2000 mg/kg. Prehysterectomy trials on 10 patients to evaluate safety revealed no penetration into the tubes and normal complete blood count, renal, cardiac, and liver tests with plasma silver rising to 20 to 30 μmoles/L and returning to baseline after 4 weeks. Finally, 7 patients were treated and followed for 6 months. We followed blood values, complications, and degree of flow reduction. Six patients were well and discharged the same day; of those, all blood values were similar to the safety studies, 5 reported varying degrees of flow reduction, and 1 patient continued with menorrhagia. The seventh patient had passage of paste into the left fallopian tube and peritoneal cavity producing immediate pain. Laparoscopy showed several burns on the back of the uterus, sigmoid colon, and cul de sac. After neutralization with saline, she made a complete, uneventful recovery and became oligoamenorrheic. ConclusionSilver nitrate could be a simple, inexpensive, safe, and potentially effective agent for endometrial ablation. However, to ensure safety, the fluid delivery system described herein must be abandoned. An alternative delivery system is needed, one which precisely controls the locus of caustic action, and further testing is required for effectiveness and safety.

Ultrathin PEGylated W18O49 Nanowires as a New 980 nm‐Laser‐Driven Photothermal Agent for Efficient Ablation of Cancer Cells In Vivo

A new photothermal coupling agent for photothermal ablation (PTA) therapy of tumors is developed based on ultrathin PEGylated W18O49 nanowires. After being injected with the nanowire solution, the in vivo tumors exhibit a rapid temperature rise to 50.0 ± 0.5 °C upon irradiation with NIR laser light at a safe, low intensity (0.72 W cm(-2)) for 2 min (left-hand mouse in the figure),), resulting in the efficient PTA of cancer cells in vivo in 10 min.

Gold Nanoparticles-Decorated Silicon Nanowires as Highly Efficient Near-Infrared Hyperthermia Agents for Cancer Cells Destruction

Near-infrared (NIR) hyperthermia agents are of current interest because they hold great promise as highly efficacious tools for cancer photothermal therapy. Although various agents have been reported, a practical NIR hyperthermia agent is yet unavailable. Here, we present the first demonstration that silicon nanomaterials-based NIR hyperthermia agent, that is, gold nanoparticles-decorated silicon nanowires (AuNPs@SiNWs), is capable of high-efficiency destruction of cancer cells. AuNPs@SiNWs are found to possess strong optical absorbance in the NIR spectral window, producing sufficient heat under NIR irradiation. AuNPs@SiNWs are explored as novel NIR hyperthermia agents for photothermal ablation of tumor cells. In particular, three different cancer cells treated with AuNPs@SiNWs were completely destructed within 3 min of NIR irradiation, demonstrating the exciting potential of AuNPs@SiNWs for NIR hyperthermia agents.

Cancer Therapy: Cooperative, Nanoparticle‐Enabled Thermal Therapy of Breast Cancer (Adv. Healthcare Mater. 1/2012)

An efficient thermal ablation agent was developed by confining gold nanoshells into nanopores of silicon microparticles. On page 84, Mauro Ferrari and co-workers show how near-infrared laser light triggers enhanced heat generation of gold nanoshells, by exploiting nanoscale cooperative effects inside microparticles. A multifold increase in thermal therapy efficacy was achieved for breast cancer in cell culture and in animal tumor models.

Prussian blue nanoparticles operate as a new generation of photothermal ablation agents for cancer therapy

Herein, prussian blue nanoparticles, an ancient dye, were explored as a new generation of near-infrared laser-driven photothermal ablation agents for cancer therapy alternative to traditional agents due to their good photothermal efficiency and high photothermal stability but low cost and particularly clinically approved biosafety.

Raman spectroscopy as a detection and analysis tool for in vitro specific targeting of pancreatic cancer cells by EGF‐conjugated, single‐walled carbon nanotubes

Single-walled carbon nanotubes (SWCNTs) were covalently linked to epidermal growth factor (EGF) proteins through an esterification process that was found to be responsible for the docking of SWCNTs on the human pancreatic cancer cells (PANC-1) surface, thus providing a mechanism for the enhanced delivery and internalization of the nanotubes. Micro Raman spectroscopy and enzyme-linked immunosorbent assay were used to evaluate the delivery process and kinetics of the SWCNTs. In vitro studies indicated that the delivery kinetics of SWCNT-EGF conjugates, at a concentration of 85 µg ml(-1), to the PANC-1 cell surfaces was significant in the first 30 min of incubation, but reached a plateau with time in accordance with the establishment of equilibrium between the association and the dissociation of EGF with the cell receptors. SWCNT-EGF conjugates could act as strong thermal ablation agents and could induce higher percentages of cellular death compared with the nontargeted SWCNTs alone.

Hydrophilic Flower‐Like CuS Superstructures as an Efficient 980 nm Laser‐Driven Photothermal Agent for Ablation of Cancer Cells

Photothermal ablation (PTA) therapy has attracted much interest in recent years as a minimally invasive alternative to conventional approaches, such as surgery and chemotherapy, for therapeutic intervention of specifi c biological targets. [ 1 , 2 ] In particular, near-infrared (NIR, λ = 700–1100 nm) laser-induced PTA, which converts NIR optical energy into thermal energy, has attracted increasing attention, because the NIR laser is absorbed less by biological tissues and the typical penetration depth of the NIR (such as 980 nm) light can be several centimeters in biological tissues. [ 3 , 4 ] A prerequisite for the development of the NIR laser-induced PTA is to gain access to biocompatible and effi cient photothermal coupling agents. As the well-known NIR photothermal conversion agents, gold (Au) nanostructures, including supramolecularly assembled nanoparticles, [ 5–8 ]

Studies on near infrared optical absorption, Raman scattering, and corresponding thermal properties of single- and double-walled carbon nanotubes for possible cancer targeting and laser-based ablation

We report the photo-thermal properties of single and double wall carbon nanotubes (CNT) dispersed in various solvents with different concentrations when exposed to near infrared nm laser irradiations. All these studies were correlated to the dispersivity of CNT in various solvents. The observed temperature increase of the various nanotube solutions was found to be determined by the concentration of the optically active nanotubes, as determined from their Raman scattering spectra, which are resonant in the spectral range of the laser excitation. Such findings could significantly improve the understanding of the optically active CNT species, their overall laser induced-heating levels, and thus reducing the amount of the CNT required for bio-medical photothermal applications to limit the possible undesired cytotoxic effects that occur at high nanotube concentrations. Our studies open up the possibility of using selective species of CNT as effective low-toxic photo thermal agents for cancer targeting and ablation.

Development of an animal model for endometrial ablation using trichloroacetic acid

To develop an animal model of endometrial ablation, and to evaluate the histologic effects of trichloroacetic acid (TCA) in the uterine cavity. Experimental prospective. Department of gynecology. Thirty female adult rats. Animals were submitted to injection of TCA in one uterine horn and saline solution in the other. Group 1 was sacrificed the day after the procedure. Group 2 was sacrificed in phase of diestrus. Superficial epithelia of the endometrium, stromal thickness, endometrial glands, and myometrium thickness were compared among the uterine horns of the same rats of group 1. The same evaluation was performed in group 2. Endometrial regeneration was evaluated. Histologic effects. In group 1, histologic parameters showed endometrial destruction on TCA injected uterine horn. In group 2, four rats died after the procedure, and six rats had no viable material. In the rest of the group, TCA-injected uterine horns showed endometrial destruction. Superficial epithelia of the endometrium and stromal thickness were similar between TCA uterine horn from groups. However, the number of endometrial glands was higher in group 1. The study developed an experimental model for endometrial ablation. TCA acid is a potent agent for endometrial ablation in rat model. No endometrial regeneration was observed after recovery of cycle.

Multifunctional NaYF4 : Yb3+,Er3+@Ag core/shell nanocomposites: integration of upconversion imaging and photothermal therapy

Here we present the synthesis of core–shell structured hexagonal-phase NaYF4 : Yb3+,Er3+@Ag nanoparticles (NPs) and their unique bio-functional properties. The structure and morphology of the NPs are confirmed by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and Fourier transform infrared (FT-IR) measurements. They displayed both strong 2H11/2/4S3/2–4I15/2 (green) and 4F9/2–4I15/2 (red) upconversion luminescence (UCL) and photothermal transfer properties under the excitation of a continuous 980 nm laser diode. Furthermore, the UCL intensity ratio of 2H11/2–4I15/2 to 4S3/2–4I15/2 acted as a temperature sensor due to the low energy gap between 2H11/2 and 4S3/2 (∼740 cm−1). After coating with the silver shell, the cytotoxicity of the composite NPs was reduced largely in contrast to the pure NaYF4 : Yb3+,Er3+ NPs. HepG2 cells from human hepatic cancer and BCap-37 cells from human breast cancer incubated with the composite NPs in vitro were found to undergo photothermally induced death on exposure to 980 nm NIR light, and the optimum mortality approaches 95% with a power density of 1.5 W cm−2 which is much lower than that reported for Au nanoshells and Au nanorods. Overall, this class of core/shell NPs is expected to be an attractive therapeutic agent for tumor ablation with bioimaging and thermal detection in real time.

A Chelator-Free Multifunctional [64Cu]CuS Nanoparticle Platform for Simultaneous Micro-PET/CT Imaging and Photothermal Ablation Therapy

We synthesized and evaluated a novel class of chelator-free [(64)Cu]CuS nanoparticles (NPs) suitable both for PET imaging and as photothermal coupling agents for photothermal ablation. These [(64)Cu]CuS NPs are simple to make, possess excellent stability, and allow robust noninvasive micro-PET imaging. Furthermore, the CuS NPs display strong absorption in the near-infrared (NIR) region (peak at 930 nm); passive targeting prefers the tumor site, and mediated ablation of U87 tumor cells occurs upon exposure to NIR light both in vitro and in vivo after either intratumoral or intravenous injection. The combination of small diameter (∼11 nm), strong NIR absorption, and integration of (64)Cu as a structural component makes these [(64)Cu]CuS NPs ideally suited for multifunctional molecular imaging and therapy.

An in vitro Study of a Phase-Shift Nanoemulsion: A Potential Nucleation Agent for Bubble-Enhanced HIFU Tumor Ablation

Phase-shift nanoemulsions have the potential to nucleate bubbles and enhance high-intensity focused ultrasound (HIFU) cancer therapy. This emulsion consists of albumin-coated dodecafluoropentane (DDFP) droplets with a mean diameter of approximately 260 nm at 37°C. It is known that superheated perfluorocarbon droplets can be vaporized with microsecond long ultrasound pulses if the acoustic pressure exceeds a specific threshold. In addition, it is well documented that particles smaller than 400 nm can extravasate through leaky tumor vessels and accumulate in the tumor interstitial space. Thus, nanoemulsions may passively target solid tumors, thus localizing cavitation nuclei for bubble-enhanced HIFU-mediated heating. In this study, we investigate the acoustic droplet vaporization of a DDFP nanoemulsion in tissue-mimicking gels and demonstrate the ability to nucleate inertial cavitation (IC) and enhance HIFU-mediated heating. The nanoemulsion was dispersed throughout albumin-acrylamide gel phantoms and sonicated with microsecond-length HIFU pulses ( f = 2 MHz). The pressure threshold needed to vaporize the nanoemulsion was measured as a function of degree of superheat, pulse length and nanoemulsion concentration. It was determined that the vaporization threshold was inversely proportional with degree of superheat and independent of pulse length and concentration within the range of values tested. It was also shown that the bubbles formed from vaporized nanoemulsions reduced the IC threshold in the gel phantoms. Finally, it was demonstrated that cavitation from vaporized nanoemulsions accelerated HIFU-mediated heating. The results from this study demonstrate that phase-shift nanoemulsions can be combined with HIFU to provide a high degree of spatial and temporal control of bubble-enhanced heating. (E-mail: tmp@bu.edu)