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1.
Neurourol Urodyn ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38934488

ABSTRACT

AIMS: Urogynecology and Reconstructive Pelvic Surgery (URPS) fellowship can be pursued after completion of either a urology (URO) or obstetrics and gynecology (GYN) residency. Our aim is to determine differences in graduating fellow cohort (GFC) case logs between URO- and GYN-based URPS programs. METHODS: Accreditation Council for Graduate Medical Education case logs for URPS GFCs in both GYN- and URO-based programs were analyzed for the 2019-2023 academic years (AY). Unpaired t-tests with Welch's correction were used to compare annual mean logged cases between URO- versus GYN-based GFCs for select surgical categories and the top 11 most logged index cases. RESULTS: GYN-based GFCs logged more cases for all pelvic organ prolapse (POP) categories including surgery on apical POP, anterior wall POP, and posterior wall POP (all p < 0.01), while URO-based GFCs logged more cases for surgery on the urinary system (p = 0.03). For the top 11 logged procedures, URO-based GFCs logged more sacral neuromodulation cases (p = 0.02), whereas GYN-based GFCs logged more slings, vaginal hysterectomies, minimally-invasive hysterectomies, vaginal apical POP, vaginal posterior POP, vaginal anterior POP, and minimally-invasive apical POP cases (all p < 0.01). There was no difference between URO- and GYN-based GFCs for complex urodynamics, cystoscopy with botox injection, or periurethral injection cases. CONCLUSIONS: URO-based URPS fellows tend to graduate with more surgery on the urinary system and sacral neuromodulation cases, while GYN-based fellows perform more slings, hysterectomies, and POP surgery. These findings may help fellowships better understand potential differences in training among graduates from URO- and GYN-based programs and encourage collaboration to lessen these discrepancies.

2.
Urogynecology (Phila) ; 30(6): 557-563, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38118059

ABSTRACT

IMPORTANCE: Millions of people rely on social media platforms, including TikTok, for health-related information. TikTok has not yet been evaluated as an information source for overactive bladder (OAB) third-line therapies. OBJECTIVES: Our aim was to assess TikTok videos on third-line therapies for OAB for misinformation and quality. STUDY DESIGN: In this cross-sectional analysis, we abstracted the top 50 TikTok videos for keywords: "Axonics," "sacral neuromodulation," "Interstim," "PTNS," "posterior tibial nerve stimulation," and "bladder Botox." Videos were scored for quality by 3 independent reviewers using the Medical Quality Video Evaluation Tool (MQ-VET). Two reviewers determined if videos contained misinformation. RESULTS: Of 300 videos screened, 119 videos were included. Twenty-four (21%) were created by medical professionals (MPs). Medical professional videos were more frequently shared (5 vs 1, P < 0.01) but had similar views, likes, comments, and length. Although MP videos had significantly higher MQ-VET scores (43 vs 27, P < 0.01), there was no difference in the rate of misinformation between MP and non-MP videos (21% vs 18%). Twenty-two videos (18.4%) contained misinformation, which were 3 times longer (50.5 vs 15 seconds, P < 0.01) and had higher MQ-VET scores (34.5 vs 27, P = 0.03) than those without misinformation. Common themes of misinformation pertained to therapy indication, mechanism of action, and patient limitations after undergoing therapy. CONCLUSIONS: Many TikTok videos on OAB third-line therapies contain misinformation. Most of these videos were not of high quality and created by the public. Medical professionals should be aware of misinformation permeating TikTok, given its large audience, and aim to promote or offer educational material of better accuracy and quality.


Subject(s)
Social Media , Urinary Bladder, Overactive , Video Recording , Urinary Bladder, Overactive/therapy , Humans , Cross-Sectional Studies , Consumer Health Information
3.
Urology ; 174: 23-27, 2023 04.
Article in English | MEDLINE | ID: mdl-36758731

ABSTRACT

OBJECTIVE: To re-examine and improve the cystoscopy process for women based on patient input. While cystoscopy is a common urological procedure, women perceive it as invasive, personal, and fear-inducing. Patients want to be treated as individuals and not just another "procedure." METHODS: Women's perspectives on cystoscopy were collected using experience-based design. Observations and timings, emotion word lists, debrief forms, patient surveys, simulation, and interviews were used. A structured 2-day quality improvement event included both in-person and virtual patient participation to gain a deeper understanding of patients' perspectives. Ideas for process improvements were generated using brainstorming, creativity exercises, and prioritization. These changes were implemented and refined using an iterative process based on feedback. RESULTS: Patients who reported feeling grateful for the positive impact of their care tended to minimize procedure-associated wait times, inconvenience, and discomfort. Women in the evaluation phase of their treatment and those who were unhappy with their symptoms tended to magnify the negative emotions associated with their procedure. Patient feedback and areas for improvement specific to women's needs were identified. Actionable changes were implemented including engaging clinic staff, updating the cystoscopy workflow, and physical changes to enhance patient privacy. CONCLUSION: Identifying and addressing the needs of women undergoing cystoscopy improves satisfaction as their emotional, physical, and knowledge-based needs are addressed. Active participation in the health care process empowers patients to have a voice in their care. An extraordinary experience with cystoscopy may decrease anxiety of the unknown and help patients have control over the experience.


Subject(s)
Cystoscopy , Patient Satisfaction , Humans , Female , Emotions , Ambulatory Care Facilities , Patient-Centered Care
4.
Urology ; 168: 35-40, 2022 10.
Article in English | MEDLINE | ID: mdl-35809700

ABSTRACT

OBJECTIVE: To describe and assess the quality and accuracy of the most highly viewed YouTube and TikTok posts related to urinary tract infections (UTIs). Social media is increasingly a resource for health information. YouTube and TikTok videos are highly utilized and are potentially a source of helpful information or misinformation. METHODS: During January 2021, "UTI" was searched within YouTube and TikTok and the most relevant videos were identified and analyzed for their content. Accuracy of scientific information, possible misinformation, and credibility of the videos was rated independently by three reviewers. Posts were categorized as educational/informational, shared experience, humor/entertainment, and home remedies/alternative therapies. RESULTS AND CONCLUSIONS: In 50 YouTube and 50 TikTok videos respectively, the median number of views was 49K and 1.4M, the median number of likes was 296 and 58K, and the median number of comments was 50 and 616. The proportion of female to male presenters was equal for YouTube videos while 94% of those from TikTok were female. Overall, YouTube videos had higher median scores for scientific information, credibility, and less misinformation compared to TikTok. YouTube videos with more views, likes, and comments tended to have lower scores in all categories and more misinformation. More presenters were medical professionals on YouTube videos than those on TikTok. While videos from both platforms contained misinformation, none promoted misinformation that would cause harm to health. Healthcare providers should be aware of the potential influence of social media as patients are getting health information from many sources.


Subject(s)
Social Media , Urinary Tract Infections , Humans , Female , Male , Information Dissemination , Video Recording , Communication
5.
J Urol ; 204(6): 1284-1289, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32924823

ABSTRACT

PURPOSE: The relationship between fluid intake and lower urinary tract symptoms in individuals with neurogenic bladder is unknown. We investigated the association between fluid intake and urinary symptoms in patients with multiple sclerosis. MATERIALS AND METHODS: A prospective cross-sectional study of patients with multiple sclerosis presenting to the neurology office was conducted. Fluid intake and lower urinary tract symptoms were assessed by the questionnaire based voiding diary and the American Urological Association Symptom Score, respectively. The relationship between fluid intake and lower urinary tract symptoms was assessed using univariate and multivariate analyses. RESULTS: Among 200 individuals with multiple sclerosis the mean total daily fluid intake was 2,489 ml (SD 1,883) and did not differ according to severity (ie mild, moderate, severe) of lower urinary tract symptoms (F=0.30, p=0.74). Fluid restricting behavior to control urinary symptoms was reported by 47% of subjects. Subjects who reported fluid restricting were more likely to have worse urinary symptoms (OR 1.95, 95% CI 1.53-2.47, p <0.01). After accounting for fluid restricting behavior on multivariate analysis, there was a minimal relationship between caffeinated fluid intake and lower urinary tract symptom severity (OR 1.00, 95% CI 1.00-1.01, p=0.01), and there was no relationship between total fluid intake and lower urinary tract symptom severity (OR 1.00, 95% CI 1.00-1.00, p=0.07). CONCLUSIONS: Caffeinated fluid intake has a minimal effect on lower urinary tract symptoms in patients with multiple sclerosis. On average, patients with multiple sclerosis do not hydrate excessively and a considerable proportion restrict fluid intake to control urinary symptoms. Fluid intake may not contribute considerably to lower urinary tract symptoms in patients with multiple sclerosis.


Subject(s)
Beverages/statistics & numerical data , Drinking/physiology , Lower Urinary Tract Symptoms/diagnosis , Multiple Sclerosis/complications , Urinary Bladder, Neurogenic/etiology , Adult , Beverages/adverse effects , Caffeine/adverse effects , Cross-Sectional Studies , Female , Humans , Lower Urinary Tract Symptoms/etiology , Lower Urinary Tract Symptoms/prevention & control , Male , Middle Aged , Multiple Sclerosis/physiopathology , Prospective Studies , Severity of Illness Index , Urinary Bladder/physiopathology , Urinary Bladder, Neurogenic/physiopathology , Urination/physiology
6.
Urol Clin North Am ; 46(1): 113-121, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30466696

ABSTRACT

The number of surgeries for pelvic organ prolapse in the United States is increasing. Abdominal sacrocolpopexy has become the gold standard for women desiring a restorative repair of their apical pelvic organ prolapse. Despite the associated morbidity of abdominal sacrocolpopexy, advances in minimally invasive approaches have safely increased the number of these surgeries performed, especially among urologists. Moreover, a number of studies have demonstrated superior objective outcomes after abdominal sacrocolpopexy when compared with vaginal approaches. Variations in the technique are described, but no consensus exists on a standard approach.


Subject(s)
Gynecologic Surgical Procedures/methods , Hysterectomy , Minimally Invasive Surgical Procedures/methods , Pelvic Organ Prolapse/surgery , Postoperative Complications/surgery , Female , Humans , Laparoscopy , Pelvic Organ Prolapse/etiology , Postoperative Complications/etiology , Robotic Surgical Procedures , Surgical Mesh
7.
Curr Urol Rep ; 19(5): 32, 2018 Mar 26.
Article in English | MEDLINE | ID: mdl-29582185

ABSTRACT

PURPOSE OF REVIEW: Chronic pelvic pain is a heterogeneous condition that often requires multiple physician visits and various treatments prior to achieving an acceptable management strategy. Neuromodulation has been used to treat chronic pelvic pain that has failed other therapies. RECENT FINDINGS: Numerous modalities of neuromodulation have been used to alleviate chronic pelvic pain with promising results. Numerous modalities of neuromodulation have demonstrated efficacy in the management of pelvic pain. Further investigation is needed to elucidate the most effective treatment modality and to identify the patients who would benefit most from this therapy.


Subject(s)
Chronic Pain/therapy , Pelvic Pain/therapy , Transcutaneous Electric Nerve Stimulation/methods , Humans , Treatment Outcome
8.
Sci Transl Med ; 9(409)2017 Sep 27.
Article in English | MEDLINE | ID: mdl-28954927

ABSTRACT

The recent Zika virus (ZIKV) outbreak demonstrates that cost-effective clinical diagnostics are urgently needed to detect and distinguish viral infections to improve patient care. Unlike dengue virus (DENV), ZIKV infections during pregnancy correlate with severe birth defects, including microcephaly and neurological disorders. Because ZIKV and DENV are related flaviviruses, their homologous proteins and nucleic acids can cause cross-reactions and false-positive results in molecular, antigenic, and serologic diagnostics. We report the characterization of monoclonal antibody pairs that have been translated into rapid immunochromatography tests to specifically detect the viral nonstructural 1 (NS1) protein antigen and distinguish the four DENV serotypes (DENV1-4) and ZIKV without cross-reaction. To complement visual test analysis and remove user subjectivity in reading test results, we used image processing and data analysis for data capture and test result quantification. Using a 30-µl serum sample, the sensitivity and specificity values of the DENV1-4 tests and the pan-DENV test, which detects all four dengue serotypes, ranged from 0.76 to 1.00. Sensitivity/specificity for the ZIKV rapid test was 0.81/0.86, respectively, using a 150-µl serum input. Serum ZIKV NS1 protein concentrations were about 10-fold lower than corresponding DENV NS1 concentrations in infected patients; moreover, ZIKV NS1 protein was not detected in polymerase chain reaction-positive patient urine samples. Our rapid immunochromatography approach and reagents have immediate application in differential clinical diagnosis of acute ZIKV and DENV cases, and the platform can be applied toward developing rapid antigen diagnostics for emerging viruses.


Subject(s)
Antigens, Viral/blood , Dengue Virus/immunology , Serogroup , Zika Virus/immunology , Amino Acid Sequence , Antibodies, Monoclonal/immunology , Antigens, Viral/isolation & purification , Chromatography, Affinity , Epitope Mapping , Humans , ROC Curve , Reproducibility of Results , Sensitivity and Specificity , Sequence Alignment
9.
J Immunoassay Immunochem ; 38(4): 355-377, 2017.
Article in English | MEDLINE | ID: mdl-27982728

ABSTRACT

Point-of-care (POC) diagnostics such as lateral flow and dipstick immunoassays use gold nanoparticle (NP)-antibody conjugates for visual readout. We investigated the effects of NP conjugation, surface chemistries, and antibody immobilization methods on dipstick performance. We compared orientational, covalent conjugation, electrostatic adsorption, and a commercial conjugation kit for dipstick assays to detect dengue virus NS1 protein. Assay performance depended significantly on their conjugate properties. We also tested arrangements of multiple test lines within strips. Results show that orientational, covalent conjugation with PEG shield could improve NS1 detection. These approaches can be used to optimize immunochromatographic detection for a range of biomarkers.


Subject(s)
Antibodies/chemistry , Antibodies/immunology , Immunoassay/methods , Metal Nanoparticles/chemistry , Viral Nonstructural Proteins/analysis , Gold/chemistry , Humans , Viral Nonstructural Proteins/immunology
10.
Development ; 143(8): 1351-62, 2016 Apr 15.
Article in English | MEDLINE | ID: mdl-27095495

ABSTRACT

Neurons display a striking degree of functional and morphological diversity, and the developmental mechanisms that underlie diversification are of significant interest for understanding neural circuit assembly and function. We find that the morphology of Drosophila sensory neurons is diversified through a series of suppressive transcriptional interactions involving the POU domain transcription factors Pdm1 (Nubbin) and Pdm2, the homeodomain transcription factor Cut, and the transcriptional regulators Scalloped and Vestigial. Pdm1 and Pdm2 are expressed in a subset of proprioceptive sensory neurons and function to inhibit dendrite growth and branching. A subset of touch receptors show a capacity to express Pdm1/2, but Cut represses this expression and promotes more complex dendritic arbors. Levels of Cut expression are diversified in distinct sensory neurons by selective expression of Scalloped and Vestigial. Different levels of Cut impact dendritic complexity and, consistent with this, we show that Scalloped and Vestigial suppress terminal dendritic branching. This transcriptional hierarchy therefore acts to suppress alternative morphologies to diversify three distinct types of somatosensory neurons.


Subject(s)
Dendrites , Drosophila Proteins/metabolism , Sensory Receptor Cells/cytology , Transcription Factors/metabolism , Animals , Axons , Drosophila , Drosophila Proteins/biosynthesis , Homeodomain Proteins/metabolism , Neurogenesis , Nuclear Proteins/metabolism , POU Domain Factors/metabolism , Trans-Activators/metabolism , Transcription Factors/biosynthesis , YAP-Signaling Proteins
11.
Lab Chip ; 15(7): 1638-41, 2015 Apr 07.
Article in English | MEDLINE | ID: mdl-25672590

ABSTRACT

Rapid point-of-care (POC) diagnostic devices are needed for field-forward screening of severe acute systemic febrile illnesses. Multiplexed rapid lateral flow diagnostics have the potential to distinguish among multiple pathogens, thereby facilitating diagnosis and improving patient care. Here, we present a platform for multiplexed pathogen detection using multi-colored silver nanoplates. This design requires no external excitation source and permits multiplexed analysis in a single channel, facilitating integration and manufacturing.


Subject(s)
Dengue Virus/isolation & purification , Ebolavirus/isolation & purification , Metal Nanoparticles/chemistry , Microfluidic Analytical Techniques/instrumentation , Silver/chemistry , Virology/instrumentation , Yellow fever virus/isolation & purification , Humans , Immunoassay/instrumentation , Limit of Detection , Point-of-Care Systems , Spectrum Analysis , Virology/methods , Virus Diseases/blood , Virus Diseases/virology
12.
J Phys Chem C Nanomater Interfaces ; 119(30): 17408-17415, 2015 Jul 30.
Article in English | MEDLINE | ID: mdl-28018519

ABSTRACT

Gold nanostars (NStars) are highly attractive for biological applications due to their surface chemistry, facile synthesis and optical properties. Here, we synthesize NStars in HEPES buffer at different HEPES/Au ratios, producing NStars of different sizes and shapes, and therefore varying optical properties. We measure the extinction coefficient of the synthesized NStars at their maximum surface plasmon resonances (SPR), which range from 5.7 × 108 to 26.8 × 108 M-1cm-1. Measured values correlate with those obtained from theoretical models of the NStars using the discrete dipole approximation (DDA), which we use to simulate the extinction spectra of the nanostars. Finally, because NStars are typically used in biological applications, we conjugate DNA and antibodies to the NStars and calculate the footprint of the bound biomolecules.

13.
Int J Nanomedicine ; 9: 3825-39, 2014.
Article in English | MEDLINE | ID: mdl-25143731

ABSTRACT

BACKGROUND: We have previously demonstrated the epidermal growth factor receptor (EGFR)-targeted hybrid plasmonic magnetic nanoparticles (225-NP) produce a therapeutic effect in human lung cancer cell lines in vitro. In the present study, we investigated the molecular mechanism of 225-NP-mediated antitumor activity both in vitro and in vivo using the EGFR-mutant HCC827 cell line. METHODS: The growth inhibitory effect of 225-NP on lung tumor cells was determined by cell viability and cell-cycle analysis. Protein expression related to autophagy, apoptosis, and DNA-damage were determined by Western blotting and immunofluorescence. An in vivo efficacy study was conducted using a human lung tumor xenograft mouse model. RESULTS: The 225-NP treatment markedly reduced tumor cell viability at 72 hours compared with the cell viability in control treatment groups. Cell-cycle analysis showed the percentage of cells in the G2/M phase was reduced when treated with 225-NP, with a concomitant increase in the number of cells in Sub-G1 phase, indicative of cell death. Western blotting showed LC3B and PARP cleavage, indicating 225-NP-treatment activated both autophagy- and apoptosis-mediated cell death. The 225-NP strongly induced γH2AX and phosphorylated histone H3, markers indicative of DNA damage and mitosis, respectively. Additionally, significant γH2AX foci formation was observed in 225-NP-treated cells compared with control treatment groups, suggesting 225-NP induced cell death by triggering DNA damage. The 225-NP-mediated DNA damage involved abrogation of the G2/M checkpoint by inhibiting BRCA1, Chk1, and phospho-Cdc2/CDK1 protein expression. In vivo therapy studies showed 225-NP treatment reduced EGFR phosphorylation, increased γH2AX foci, and induced tumor cell apoptosis, resulting in suppression of tumor growth. CONCLUSION: The 225-NP treatment induces DNA damage and abrogates G2/M phase of the cell cycle, leading to cellular apoptosis and suppression of lung tumor growth both in vitro and in vivo. Our findings provide a rationale for combining 225-NP with other DNA-damaging agents for achieving enhanced anticancer activity.


Subject(s)
Antineoplastic Agents/pharmacology , DNA Damage/drug effects , ErbB Receptors/metabolism , G2 Phase Cell Cycle Checkpoints/drug effects , Lung Neoplasms/metabolism , Magnetite Nanoparticles/chemistry , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/toxicity , Apoptosis/drug effects , Autophagy/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Female , Humans , Magnetite Nanoparticles/toxicity , Mice , Mice, Nude , Xenograft Model Antitumor Assays
14.
PLoS One ; 6(11): e25507, 2011.
Article in English | MEDLINE | ID: mdl-22087216

ABSTRACT

BACKGROUND: The epidermal growth factor receptor (EGFR) is overexpressed in 80% of non-small cell lung cancer (NSCLC) and is associated with poor survival. In recent years, EGFR-targeted inhibitors have been tested in the clinic for NSCLC. Despite the emergence of novel therapeutics and their application in cancer therapy, the overall survival rate of lung cancer patients remains 15%. To develop more effective therapies for lung cancer we have combined the anti-EGFR antibody (Clone 225) as a molecular therapeutic with hybrid plasmonic magnetic nanoparticles (NP) and tested on non-small cell lung cancer (NSCLC) cells. METHODOLOGY/PRINCIPAL FINDINGS: Cell viability was determined by trypan-blue assay. Cellular protein expression was determined by Western blotting. C225-NPs were detected by electron microscopy and confocal microscopy, and EGFR expression using immunocytochemistry. C225-NP exhibited a strong and selective antitumor effect on EGFR-expressing NSCLC cells by inhibiting EGFR-mediated signal transduction and induced autophagy and apoptosis in tumor cells. Optical images showed specificity of interactions between C225-NP and EGFR-expressing NSCLC cells. No binding of C225-NP was observed for EGFR-null NSCLC cells. C225-NP exhibited higher efficiency in induction of cell killing in comparison with the same amount of free C225 antibody in tumor cells with different levels of EGFR expression. Furthermore, in contrast to C225-NP, free C225 antibody did not induce autophagy in cells. However, the therapeutic efficacy of C225-NP gradually approached the level of free antibodies as the amount of C225 antibody conjugated per nanoparticle was decreased. Finally, attaching C225 to NP was important for producing the enhanced tumor cell killing as addition of mixture of free C225 and NP did not demonstrate the same degree of cell killing activity. CONCLUSIONS/SIGNIFICANCE: We demonstrated for the first time the molecular mechanism of C225-NP induced cytotoxic effects in lung cancer cells that are not characteristic for free molecular therapeutics thus increasing efficacy of therapy against NSCLC.


Subject(s)
Antibodies, Neoplasm/therapeutic use , Apoptosis/drug effects , Autophagy/drug effects , Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/antagonists & inhibitors , Magnetite Nanoparticles/therapeutic use , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Drug Evaluation, Preclinical , Humans , Neoplasm Proteins/antagonists & inhibitors
15.
Langmuir ; 27(12): 7681-90, 2011 Jun 21.
Article in English | MEDLINE | ID: mdl-21591638

ABSTRACT

The ability of smaller than 100 nm antibody (Ab) nanoparticle conjugates to target and modulate the biology of specific cell types may enable major advancements in cellular imaging and therapy in cancer. A key challenge is to load a high degree of targeting, imaging, and therapeutic functionality into small, yet stable particles. A versatile method called thin autocatalytic growth on substrate (TAGs) has been developed in our previous study to form ultrathin and asymmetric gold coatings on iron oxide nanocluster cores producing exceptional near-infrared (NIR) absorbance. AlexaFluor 488 labeled Abs were used to correlate the number of Abs conjugated to iron oxide/gold nanoclusters (nanoroses) with the hydrodynamic size. A transition from submonolayer to multilayer aggregates of Abs on the nanorose surface was observed for 54 Abs and an overall particle diameter of ∼60-65 nm. The hydrodynamic diameter indicated coverage of a monolayer of 54 Abs, in agreement with the prediction of a geometric model, by assuming a circular footprint of 16.9 nm diameter per Ab molecule. The targeting efficacy of nanoclusters conjugated with monoclonal Abs specific for epidermal growth factor receptor (EGFR) was evaluated in A431 cancer cells using dark field microscopy and atomic absorbance spectrometry (AAS) analysis. Intense NIR scattering was achieved from both high uptake of nanoclusters in cells and high intrinsic NIR absorbance of individual nanoclusters. Dual mode imaging with dark field reflectance microscopy and fluorescence microscopy indicates the Abs remained attached to the Au surfaces upon the uptake by the cancer cells. The ability to load intense multifunctionality, specifically strong NIR absorbance, conjugation of an Ab monolayer in addition to a strong r2 MRI contrast that was previously demonstrated in a total particle size of only 63 nm, is an important step forward in development of theranostic agents for combined molecular specific imaging and therapy.


Subject(s)
Antibodies/immunology , ErbB Receptors/immunology , Nanostructures , Cell Line, Tumor , Humans , Microscopy, Fluorescence , Spectrophotometry, Ultraviolet
16.
Opt Lett ; 35(22): 3751-3, 2010 Nov 15.
Article in English | MEDLINE | ID: mdl-21081985

ABSTRACT

Plasmonic metal nanoparticles are used in photoacoustic imaging as contrast agents because of their resonant optical absorption properties in the visible and near-IR regions. However, the nanoparticles could accumulate and result in long-term toxicity in vivo, because they are generally not biodegradable. Recently, biodegradable plasmonic gold nanoclusters, consisting of sub-5 nm primary gold nanoparticles and biodegradable polymer stabilizer, were introduced. In this Letter, we demonstrate the feasibility of biodegradable nanoclusters as a photoacoustic contrast agent. We performed photoacoustic and ultrasound imaging of a tissue-mimicking phantom with inclusions containing nanoclusters at various concentrations. The results indicate that the biodegradable gold nanoclusters can be used as effective contrast agents in photoacoustic imaging.


Subject(s)
Contrast Media , Gold , Metal Nanoparticles , Nanocomposites , Surface Plasmon Resonance , Acoustics , Feasibility Studies , Phantoms, Imaging , Ultrasonics
17.
ACS Nano ; 4(4): 2178-84, 2010 Apr 27.
Article in English | MEDLINE | ID: mdl-20373747

ABSTRACT

Metal nanoparticles with surface plasmon resonance (SPR) in the near-infrared region (NIR) are of great interest for imaging and therapy. Presently, gold nanoparticles with NIR absorbance are typically larger than 50 nm, above the threshold size of approximately 5 nm required for efficient renal clearance. As these nanoparticles are not biodegradable, concerns about long-term toxicity have restricted their translation into the clinic. Here, we address this problem by developing a flexible platform for the kinetically controlled assembly of sub-5 nm ligand-coated gold particles to produce metal/polymer biodegradable nanoclusters smaller than 100 nm with strong NIR absorbance for multimodal application. A key novel feature of the proposed synthesis is the use of weakly adsorbing biodegradable polymers that allows tight control of nanocluster size and, in addition, results in nanoclusters with unprecedented metal loadings and thus optical functionality. Over time, the biodegradable polymer stabilizer degrades under physiological conditions that leads to disassembly of the nanoclusters into sub-5 nm primary gold particles which are favorable for efficient body clearance. This synthesis of polymer/inorganic nanoclusters combines the imaging contrast and therapeutic capabilities afforded by the NIR-active nanoparticle assembly with the biodegradability of a polymer stabilizer.


Subject(s)
Infrared Rays , Molecular Imaging/methods , Nanocomposites/chemistry , Polymers/metabolism , Polymers/therapeutic use , Surface Plasmon Resonance , Adsorption , Animals , Cell Line , Gold/chemistry , Kinetics , Lactic Acid/chemistry , Metal Nanoparticles/chemistry , Mice , Polyesters , Polyethylene Glycols/chemistry , Polymers/chemistry , Polymers/toxicity
18.
J Biomed Opt ; 15(1): 015003, 2010.
Article in English | MEDLINE | ID: mdl-20210443

ABSTRACT

The clinical applicability of antibodies and plasmonic nanosensors as topically applied, molecule-specific optical diagnostic agents for noninvasive early detection of cancer and precancer is severely limited by our inability to efficiently deliver macromolecules and nanoparticles through mucosal tissues. We have developed an imidazole-functionalized conjugate of the polysaccharide chitosan (chitosan-IAA) to enhance topical delivery of contrast agents, ranging from small molecules and antibodies to gold nanoparticles up to 44 nm in average diameter. Contrast agent uptake and localization in freshly resected mucosal tissues was monitored using confocal microscopy. Chitosan-IAA was found to reversibly enhance mucosal permeability in a rapid, reproducible manner, facilitating transepithelial delivery of optical contrast agents. Permeation enhancement occurred through an active process, resulting in the delivery of contrast agents via a paracellular or a combined paracellular/transcellular route depending on size. Coadministration of epidermal growth factor receptor-targeted antibodies with chitosan-IAA facilitated specific labeling and discrimination between paired normal and malignant human oral biopsies. Together, these data suggest that chitosan-IAA is a promising topical permeation enhancer for mucosal delivery of optical contrast agents.


Subject(s)
Chitosan/administration & dosage , Contrast Media/administration & dosage , Imidazoles/chemistry , Nanoparticles/chemistry , Administration, Topical , Animals , Chitosan/chemistry , Chitosan/pharmacokinetics , Contrast Media/chemistry , Contrast Media/pharmacokinetics , Epithelium/metabolism , ErbB Receptors/metabolism , Guinea Pigs , Humans , Imidazoles/administration & dosage , Microscopy, Confocal , Mouth Mucosa/metabolism , Neoplasms/diagnosis , Neoplasms/metabolism , Permeability , Recovery of Function , Urinary Bladder/metabolism
19.
Article in English | MEDLINE | ID: mdl-19964034

ABSTRACT

Nanotechnology offers unique opportunities for cancer detection, therapy and the ability to monitor therapeutic interventions. This potential has to be analyzed in context of challenges that need to be overcome in translation of nanoparticles to clinical applications including specific delivery in tissues and clearance from the body. Here, we will present a case study of plasmonic nanoparticles in cancer imaging and therapy.


Subject(s)
Metal Nanoparticles/therapeutic use , Neoplasms/diagnosis , Neoplasms/therapy , Contrast Media , ErbB Receptors/analysis , Humans , Inorganic Chemicals/therapeutic use , Magnetic Resonance Imaging , Matrix Metalloproteinases/analysis , Nanotechnology , Neoplasms/enzymology , Surface Plasmon Resonance
20.
ACS Nano ; 3(9): 2686-96, 2009 Sep 22.
Article in English | MEDLINE | ID: mdl-19711944

ABSTRACT

The ability of 20-50 nm nanoparticles to target and modulate the biology of specific types of cells will enable major advancements in cellular imaging and therapy in cancer and atherosclerosis. A key challenge is to load an extremely high degree of targeting, imaging, and therapeutic functionality into small, yet stable particles. Herein we report approximately 30 nm stable uniformly sized near-infrared (NIR) active, superparamagnetic nanoclusters formed by kinetically controlled self-assembly of gold-coated iron oxide nanoparticles. The controlled assembly of nanocomposite particles into clusters with small primary particle spacings produces collective responses of the electrons that shift the absorbance into the NIR region. The nanoclusters of approximately 70 iron oxide primary particles with thin gold coatings display intense NIR (700-850 nm) absorbance with a cross section of approximately 10(-14) m(2). Because of the thin gold shells with an average thickness of only 2 nm, the r(2) spin-spin magnetic relaxivity is 219 mM(-1) s(-1), an order of magnitude larger than observed for typical iron oxide particles with thicker gold shells. Despite only 12% by weight polymeric stabilizer, the particle size and NIR absorbance change very little in deionized water over 8 months. High uptake of the nanoclusters by macrophages is facilitated by the dextran coating, producing intense NIR contrast in dark field and hyperspectral microscopy, both in cell culture and an in vivo rabbit model of atherosclerosis. Small nanoclusters with optical, magnetic, and therapeutic functionality, designed by assembly of nanoparticle building blocks, offer broad opportunities for targeted cellular imaging, therapy, and combined imaging and therapy.


Subject(s)
Atherosclerosis/pathology , Atherosclerosis/therapy , Ferric Compounds/chemistry , Ferric Compounds/metabolism , Gold/chemistry , Macrophages/metabolism , Nanoparticles/chemistry , Animals , Aorta/metabolism , Aorta/pathology , Atherosclerosis/metabolism , Biological Transport , Cell Line , Humans , Magnetics , Particle Size , Rabbits , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Surface Properties
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