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1.
Int J Toxicol ; 35(1): 38-46, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26296672

RESUMO

To evaluate the clinical safety profile for the use of gold nanoshells in patients with human prostate cancer. This follows on the nonclinical safety assessment of the AuroShell particles reported previously. Twenty-two patients, with biopsy diagnosed prostate cancer, underwent nanoshell infusion and subsequent radical prostatectomy (RRP). Fifteen of these patients had prostates that were additionally irradiated by a single-fiber laser ablation in each prostate hemisphere prior to RRP. Patients in the study were assessed at 9 time points through 6 months postinfusion. Adverse events were recorded as reported by the patients and from clinical observation. Blood and urine samples were collected at each patient visit and subjected to chemical (16 tests), hematological (23 tests), immunological (3 tests, including total PSA), and urinalysis (8 tests) evaluation. Temperature of the anterior rectal wall at the level of the prostate was measured. The study, recorded 2 adverse events that were judged attributable to the nanoparticle infusion: (1) an allergic reaction resulting in itching, which resolved with intravenous antihistamines, and (2) in a separate patient, a transient burning sensation in the epigastrium. blood/hematology/urinalysis assays indicated no device-related changes. No change in temperature of the anterior rectal wall was recorded in any of the patients. The clinical safety profile of AuroShell particles is excellent, matching nonclinical findings. A recent consensus statement suggested that the published literature does not support a preference for any ablation technique over another.(1) Now that clinical safety has been confirmed, treatment efficacy of the combined infusion plus laser ablation in prostate will be evaluated in future studies using imaging modalities directing the laser against identified prostate tumors.


Assuntos
Hipertermia Induzida , Nanoconchas , Fototerapia , Neoplasias da Próstata/terapia , Humanos , Masculino , Projetos Piloto
2.
Nanomaterials (Basel) ; 14(15)2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39120366

RESUMO

AuroLase® Therapy-a nanoparticle-enabled focal therapy-has the potential to safely and effectively treat localized prostate cancer (PCa), preserving baseline functionality. This article presents a detailed case of localized PCa treated with AuroLase, providing insight on expectations from the diagnosis of PCa to one year post-treatment. AuroLase Therapy is a two-day treatment consisting of a systemic infusion of gold nanoshells (~150-nm hydrodynamic diameter) on Day 1, and sub-ablative laser treatment on Day 2. Multiparametric MRI (mpMRI) was used for tumor visualization, treatment planning, and therapy response assessment. The PCa was targeted with a MR/Ultrasound-fusion (MR/US) transperineal approach. Successful treatment was confirmed at 6 and 12 months post-treatment by the absence of disease in MR/US targeted biopsies. On the mpMRI, confined void space was evident, an indication of necrotic tissues encompassing the treated lesion, which was completely resolved at 12 months, forming a band-like scar with no evidence of recurrent tumor. The patient's urinary and sexual functions were unchanged. During the one-year follow-up, changes on the DCE sequence and in the Ktrans and ADC values assist in qualitatively and quantitatively evaluating tissue changes. The results highlight the potential of gold-nanoparticle-enabled sub-ablative laser treatment to target and control localized PCa, maintain quality of life, and preserve baseline functionality.

3.
Int J Toxicol ; 31(6): 584-94, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23212452

RESUMO

Gold nanoshells (155 nm in diameter with a coating of polyethylene glycol 5000) were evaluated for preclinical biocompatibility, toxicity, and biodistribution as part of a program to develop an injectable device for use in the photothermal ablation of tumors. The evaluation started with a complete good laboratory practice (GLP) compliant International Organization for Standardization (ISO)-10993 biocompatibility program, including cytotoxicity, pyrogenicity (US Pharmacopeia [USP] method in the rabbit), genotoxicity (bacterial mutagenicity, chromosomal aberration assay in Chinese hamster ovary cells, and in vivo mouse micronucleus), in vitro hemolysis, intracutaneous reactivity in the rabbit, sensitization (in the guinea pig maximization assay), and USP/ISO acute systemic toxicity in the mouse. There was no indication of toxicity in any of the studies. Subsequently, nanoshells were evaluated in vivo by intravenous (iv) infusion using a trehalose/water solution in a series of studies in mice, Sprague-Dawley rats, and Beagle dogs to assess toxicity for time durations of up to 404 days. Over the course of 14 GLP studies, the gold nanoshells were well tolerated and, when injected iv, no toxicities or bioincompatibilities were identified.


Assuntos
Antineoplásicos/toxicidade , Compostos de Ouro/toxicidade , Nanoconchas/toxicidade , Testes de Toxicidade/métodos , Animais , Antineoplásicos/uso terapêutico , Peso Corporal/efeitos dos fármacos , Células CHO , Sobrevivência Celular/efeitos dos fármacos , Aberrações Cromossômicas/induzido quimicamente , Cricetinae , DNA/efeitos dos fármacos , Cães , Feminino , Compostos de Ouro/análise , Compostos de Ouro/farmacocinética , Injeções Intravenosas , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes para Micronúcleos , Nanoconchas/uso terapêutico , Tamanho do Órgão/efeitos dos fármacos , Pigmentação/efeitos dos fármacos , Coelhos , Ratos , Ratos Sprague-Dawley , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética
4.
Int J Hyperthermia ; 27(8): 782-90, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22098362

RESUMO

Minimally invasive thermal therapy using high-power diode lasers is an active area of clinical research. Gold nanoshells (AuNS) can be tuned to absorb light in the range used for laser ablation and may facilitate more conformal tumor heating and sparing of normal tissue via enhanced tumor specific heating. This concept was investigated in a xenograft model of prostate cancer (PC-3) using MR temperature imaging (MRTI) in a 1.5T scanner to characterize the spatiotemporal temperature distribution resulting from nanoparticle mediated heating. Tumors with and without intravenously injected AuNS were exposed to an external laser tuned to 808 nm for 180 sec at 4 W/cm(2) under real-time monitoring with proton resonance frequency shift based MRTI. Microscopy indicated that these nanoparticles (140-150 nm) accumulated passively in the tumor and remained close to the tumor microvasculature. MRTI measured a statistically significant (p < 0.001) increase in maximum temperature in the tumor cortex (mean = 21 ± 7°C) in +AuNS tumors versus control tumors. Analysis of the temperature maps helped demonstrate that the overall distribution of temperature within +AuNS tumors was demonstrably higher versus control, and resulted in damage visible on histopathology. This research demonstrates that passive uptake of intravenously injected AuNS in PC-3 xenografts converts the tumor vasculature into a potent heating source for nanoparticle mediated ablation at power levels which do not generate significant damage in normal tissue. When used in conjunction with MRTI, this has implications for development and validation of more conformal delivery of therapy for interstitial laser ablations.


Assuntos
Terapia a Laser , Imageamento por Ressonância Magnética/métodos , Nanoconchas , Neoplasias da Próstata/cirurgia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Ouro , Humanos , Masculino , Camundongos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Neoplasias da Próstata/ultraestrutura , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Opt Express ; 18(25): 26535-49, 2010 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-21165005

RESUMO

Nanoparticle-assisted photo-thermal (NAPT) ablation has become a new and attractive modality for the treatment of cancerous tumors. This therapy exploits the passive accumulation of intravenously delivered optically resonant metal nanoparticles into tumors, however, the circulating bioavailability of these particles is often unknown. We present a non-invasive optical device capable of monitoring the circulation of optically resonant gold nanorods. The device, referred to as a pulse photometer, uses the technique of multi-wavelength photoplethysmography. We simultaneously report the circulation of gold nanorods and oximetry for six hours post-injection in mice with no anesthesia and remove the probe when not collecting data. The instrument shows good agreement (R(2) = 0.903, n = 30) with ex vivo spectrophotometric analysis of blood samples. The real-time feedback provided has a strong potential for reducing variability and thus improving the efficacy of similar clinical therapies.


Assuntos
Artérias/fisiologia , Análise Química do Sangue/instrumentação , Ouro/sangue , Nanotubos/análise , Oximetria/instrumentação , Oxigênio/sangue , Fotopletismografia/instrumentação , Animais , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
6.
J Phys Chem B ; 109(22): 11083-7, 2005 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-16852350

RESUMO

We report a facile and controllable method for the postfabrication texturing of the surface topography of Au nanoshells based on site-selective chemical etching of the polycrystalline Au nanoshell surface by a bifunctional alkanethiol molecule, cysteamine. This nanoscale surface texturing process systematically introduces dramatic changes to the plasmonic properties of the Au nanoshells. The modification of the plasmon resonant properties of nanoshells as a function of increased surface roughness was examined experimentally and modeled theoretically using three-dimensional finite difference time domain (FDTD) simulations.

7.
Ther Deliv ; 6(7): 777-83, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26228771

RESUMO

AIM: Gold nanoparticles are employed for imaging and treatment of surgically inaccessible tumors owing to their inherent optical absorption and ability to extravasate through intravenous distribution. These nanoparticles are cleared from the blood by the reticuloendothelial system (RES) as expected given their size. MATERIALS & METHODS: This study demonstrates the effects of RES blockade through the intravenous administration of λ-carrageenan, resulting in a decrease in the median clearance rate from 18.9 (95% CrI: 15.9-22.6) to 11.2 (95% CrI: 8.8-13.9) µl/min and an increase in nanoparticle circulation half-life t(½)( = 264 ± 73 vs 160 ± 22 min; p < 0.01). RESULTS: This 59.3% decrease in clearance is greater than the 15% previously reported for liposomes [ 1 ]. CONCLUSION: The primary benefit of nontoxic RES blockade is to increase the circulation time, where traditional particle modification is ineffective or impractical.


Assuntos
Antineoplásicos/farmacocinética , Carragenina/administração & dosagem , Ouro/farmacocinética , Nanopartículas Metálicas , Sistema Fagocitário Mononuclear/efeitos dos fármacos , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/sangue , Química Farmacêutica , Feminino , Ouro/administração & dosagem , Ouro/sangue , Meia-Vida , Injeções Intravenosas , Taxa de Depuração Metabólica , Camundongos Endogâmicos BALB C , Modelos Biológicos , Sistema Fagocitário Mononuclear/metabolismo , Nanotecnologia , Tamanho da Partícula , Fotopletismografia , Tecnologia Farmacêutica/métodos
8.
J Biomed Opt ; 15(1): 018001, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20210487

RESUMO

The photothermal ablation of solid tumors using exogenous, near-infrared (NIR)-absorbing nanoparticles has been previously investigated using various preclinical models and is currently being evaluated in the clinic. Here, we evaluate the circulation kinetics, preliminary toxicity, and efficacy of photothermal ablation of solid tumors using gold nanorods systemically delivered and passively accumulated in a murine subcutaneous colon cancer model. Tumored animals were infused with nanorods followed by the percutaneous illumination of the tumor with an 808-nm laser. Control groups consisted of laser-only, nanorod-only, and untreated tumored animals. The survival of the treated and control groups were monitored for 60 days post-treatment. The survival of the photothermally treated group was statistically longer than the control groups, with approximately 44% tumor free through the evaluation period. Histopathology of the major organs of animals infused with nanorods did not indicate any significant toxicity at 60 days post-treatment. Particle biodistribution was evaluated by elemental analysis of the major organs of untumored mice at 1, 7, and 30 days after infusion with nanorods. Elemental analysis indicates nanorod clearance from the blood and retention by the reticuloendothelial system. This study indicates that gold nanorods are promising agents for photothermal ablation of solid tumors.


Assuntos
Neoplasias do Colo/terapia , Ouro/administração & dosagem , Nanotubos/química , Fototerapia/métodos , Animais , Modelos Animais de Doenças , Ouro/química , Ouro/farmacocinética , Histocitoquímica , Estimativa de Kaplan-Meier , Terapia a Laser , Camundongos , Camundongos Endogâmicos BALB C , Nanotubos/efeitos adversos , Nanotubos/ultraestrutura , Fototerapia/efeitos adversos , Temperatura , Distribuição Tecidual
9.
J Biomed Opt ; 15(4): 047007, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20799838

RESUMO

There is an urgent clinical need to monitor the intravenous delivery and bioavailability of circulating nanoparticles used in cancer therapy. This work presents the use of photoplethysmography for the noninvasive real-time estimation of vascular gold nanoshell concentration in a murine subject. We develop a pulse photometer capable of accurately measuring the photoplethysmogram in mice and determining the ratio of pulsatile changes in optical extinction between 805 and 940 nm, commonly referred to as R. These wavelengths are selected to correspond to the extinction properties of gold nanoshells. Six 30-s measurements (5 min, 2, 4, 6, 8, 10 h) are taken under light anesthesia to observe the change in R as the nanoparticles clear from the circulation. Our model describes the linear fit (R(2)=0.85) between R and the concentration of nanoparticles measured via ex vivo spectrophotometric and instrumental neutron activation analysis. This demonstrates the utility of this technique in support of clinical nanoparticle therapies.


Assuntos
Vasos Sanguíneos/química , Ouro/sangue , Nanopartículas/análise , Fotopletismografia/instrumentação , Fotopletismografia/métodos , Animais , Desenho de Equipamento , Análise de Falha de Equipamento , Camundongos
10.
Nano Lett ; 7(2): 496-501, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17256995

RESUMO

Metallic nanoparticles are known to dramatically modify the spontaneous emission of nearby fluorescent molecules and materials. Here we examine the role of the nanoparticle plasmon resonance energy and nanoparticle scattering cross section on the fluorescence enhancement of adjacent indocyanine green (ICG) dye molecules. We find that enhancement of the molecular fluorescence by more than a factor of 50 can be achieved for ICG next to a nanoparticle with a large scattering cross section and a plasmon resonance frequency corresponding to the emission frequency of the molecule.

11.
Nano Lett ; 6(1): 16-23, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16402780

RESUMO

Temperature has been used to control the order of assembly events in a solution containing three types of particles to be linked by two different sets of complementary DNA. At higher temperatures, only the duplexes having higher thermal stability were able to form. By starting at a high temperature and then cooling the sample, these more stable sequences hybridized first, followed by the less stable sequences at lower temperatures. Because of the use of thiolated DNA on Au particles, some loss and exchange of the DNA strands occurred at elevated temperatures. However, since cooperativity favors the "correct" assemblies, Au-S bond lability did not appreciably impact the order of the assembly process. Temperature programming combines the selectivity of DNA-directed assembly with the ability to control the order in which several complementary strands hybridize in a common solution and could contribute to the synthesis of more complex nanostructured materials.


Assuntos
DNA/química , Ouro/química , Nanoestruturas , Pareamento de Bases , DNA Complementar/química , Eletroforese em Gel de Ágar , Oligonucleotídeos/química , Compostos de Sulfidrila/química , Temperatura , Termodinâmica
12.
Nano Lett ; 6(10): 2338-43, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17034107

RESUMO

The enhanced local optical fields at the surface of illuminated metallic nanoparticles and nanostructures are of intense fundamental and technological interest. Here we report a self-consistent measurement of the spatial extent of the fringing field above a plasmonic nanoparticle surface. Bifunctional DNA-based adsorbate molecules are used as nanoscale optical rulers, providing two distinct surface enhanced Raman scattering signals that vary independently in intensity as a function of distance from the nanoparticle surface. While the measurement technique is calibrated on gold nanoshell surfaces with controlled and predictable electromagnetic nanoenvironments, this approach is broadly adaptable to a wide range of plasmonic geometries.


Assuntos
DNA/análise , DNA/química , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Nanotecnologia/métodos , Ressonância de Plasmônio de Superfície/métodos , Tamanho da Partícula
13.
Langmuir ; 20(23): 10246-51, 2004 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-15518520

RESUMO

DNA:Au nanosphere bioconjugates have applications in biosensing and in the bottom-up assembly of materials. These bioconjugates can be selectively assembled into three-dimensional aggregates upon addition of complementary DNA oligonucleotides and can be dissociated by heating above a melting transition temperature at which the DNA duplexes are denatured. Herein we describe the impact of polymeric solutes on the thermal denaturation behavior of DNA:Au nanoparticle bioconjugate assemblies. Polymeric solutes can dramatically impact biochemical reactions via macromolecular crowding. Poly(ethylene glycol)s (PEGs) and dextrans of varying molecular weights were used as crowding reagents. While both PEG and dextran increased the stability of DNA:Au aggregates, melting transition temperatures in the presence of PEG were impacted more significantly. Polymer molecular weight was less important than polymer chemistry and weight percent in solution. For a high (15%) weight percent of PEG, aggregation was observed even in the absence of complementary oligonucleotides. These results underscore the importance of polymer chemistry in addition to physical volume exclusion in macromolecular crowding and point to the importance of understanding these effects when designing biorecognition-based nanoparticle assembly schemes in complex matrixes (i.e., any involving polymeric solutes).


Assuntos
DNA/química , Sequência de Bases , Biopolímeros/química , Técnicas In Vitro , Substâncias Macromoleculares , Nanoestruturas , Nanotecnologia , Desnaturação de Ácido Nucleico , Polietilenoglicóis , Espectrofotometria , Termodinâmica
14.
J Am Chem Soc ; 124(25): 7314-23, 2002 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-12071740

RESUMO

We have investigated the impact of steric effects on the hybridization and enzymatic extension of oligonucleotides bound to 12-nm colloidal Au particles. In these experiments, a nanoparticle-bound 12-mer sequence is hybridized either to its solution phase 12-mer complement or to an 88-mer template sequence. The particle-bound oligonucleotide serves as a primer for enzymatic extension reactions, in which covalent incorporation of nucleotides to form the complement of the template is achieved by the action of DNA polymerase. Primers were attached via-C(6)H(12)SH, -C(12)H(24)SH, and -TTACAATC(6)H(12)SH linkers attached at the 5' end. Primer coverage on the nanoparticles was varied by dilution with (5')HSC(6)H(12)AAA AAA(3'). Hybridization efficiencies were determined as a function of linker length, primer coverage, complement length (12-mer vs 88-mer), and primer:complement concentration ratio. In all cases, hybridization for the 88-mer was less efficient than for the 12-mer. Low primer surface coverage, greater particle-primer separation, and higher primer:complement ratios led to optimal hybridization. Hybridization efficiencies as high as 98% and 75% were observed for the 12-mer and 88-mer, respectively. Enzymatic extension of particle-bound primers was observed under all conditions tested; however, the efficiency of the reaction was strongly affected by linker length and primer coverage. Extension of primers attached by the longest linker was as efficient as the solution-phase reaction.


Assuntos
DNA Polimerase Dirigida por DNA/química , Ouro/química , Hibridização de Ácido Nucleico/métodos , Oligonucleotídeos/química , DNA/química , DNA/metabolismo , Primers do DNA , DNA Polimerase Dirigida por DNA/metabolismo , Nanotecnologia , Tamanho da Partícula
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