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Description: New York State Department of Health (NYSDOH) recommends that all pregnant patients receive human immunodeficiency virus (HIV) screening during pregnancy. This study assessed the prevalence of repeat prenatal HIV testing and factors associated with receipt of the recommended tests. Methods: Data from the NYSDOH newborn screening program were used to randomly select pregnant persons without HIV who delivered a liveborn infant in 2017. Receipt of repeat testing was defined as an initial HIV test in the first or second trimesters and the final in the third trimester (relaxed); or an initial test in the first trimester and the final in the third trimester (strict). Relative risks (RRs) and 95% confidence intervals were calculated in bivariate analyses. Adjusted RRs were calculated to determine associations between demographic and clinical factors and receipt of repeat HIV testing. Results: The cohort included 2,225 individuals. Roughly one quarter (24%) received the recommended tests in the first or second and third trimesters and 17% received them in the first and third trimesters. Individuals who reported Hispanic or Asian race/ethnicities, had government-funded insurance, started prenatal care in the first trimester, delivered in New York City, or received prenatal hepatitis C virus screening were significantly more likely to receive repeat testing using either definition. Conclusions: Despite the benefits and cost-effectiveness, the prevalence of repeat prenatal HIV screening during the third trimester remains persistently low. Improved messaging and targeted education and resources to assist prenatal providers could reinforce the importance of repeat testing and reduce residual perinatal HIV transmission.

Background and Objective: Coronavirus disease 2019 (COVID-19) necessitated a transition to virtual education which limits hands-on opportunities and student engagement. To adapt, a pilot study investigating clay modeling as an alternative educational tool for medical students was incorporated in a virtual and in-person sub-internship for prospective urology applicants. We aim to review the literature supporting the use of clay modeling in medical education as well as describe our experience with the activity as a way to engage trainees and evaluate early surgical skills., Methods: The current literature on clay modeling in medical and early surgical education was reviewed using multiple search queries in PubMed. A total of thirteen publications were identified and analyzed, with zero articles specifically discussing urological anatomy or surgery. The pilot study was conducted through the traditional in-person sub-internship as well as through a novel virtual sub-internship at a single academic U.S. Urology residency program. Students were instructed to create a three-dimensional model of a genitourinary organ using modeling clay. Anonymized surveys were collected. Responses of virtual and in-person students were compared., Key Content and Findings: Clay modeling has been shown in the literature to be beneficial in medical and early surgical education through the use of active learning. Twenty-five total virtual (N=6) and in-person (N=19) students participated in the clay modeling activity. Survey ratings were mixed, with 100% positive responses amongst the virtual group in the areas of "relevance" and "creatively challenging" compared to the in-person cohort, 31.6% of whom responded positively to "relevance" and 47.4% for "creatively challenging" respectively. Overall, students responded positively for the exercise being "creatively challenging" (n=15, 60%) and "enjoyable" (n=16, 64%). Positive results echoed the student perspectives described in the current literature on clay modeling., Conclusions: Clay modeling has previously been used in the in-person classroom setting as a learning supplement or replacement for dissection classes but has not been previously described for use in the virtual learning environment or within the field of Urology. With ongoing need to develop novel teaching modalities, clay modeling may be a unique tool to enhance learning, and evaluate technical skill, and boost engagement for medical trainees., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-57/coif). The authors have no conflicts of interest to disclose., (2024 Translational Andrology and Urology. All rights reserved.)

Background: Although naloxone is widely acknowledged as a life-saving intervention and a critical tool for first responders, there remains a need to explore how law enforcement officers have adapted to a shifting scope of work. Past research has focused mainly on officer training, their abilities to administer naloxone, and to a lesser extent on their experiences and interactions working with people who use drugs (PWUD)., Methods: A qualitative approach was used to explore officer perspectives and behaviors surrounding responses to incidents of suspected opioid overdose. Between the months of March and September 2017, semi-structured interviews were conducted with 38 officers from 17 counties across New York state (NYS)., Results: Analysis of in-depth interviews revealed that officers generally considered the additional responsibility of administering naloxone to have become "part of the job". Many officers reported feeling as though they are expected to wear multiple hats, functioning as both law enforcement and medical personnel and at times juggling contradictory roles. Evolving views on drugs and drug use defined many interviews, as well as the recognition that a punitive approach to working with PWUD is not the solution, emphasizing the need for cohesive, community-wide support strategies. Notable differences in attitudes toward PWUD appeared to be influenced by an officer's connection to someone who uses drugs and/or due to a background in emergency medical services., Conclusion: Law enforcement officers in NYS are emerging as an integral part of the continuum of care for PWUD. Our findings are capturing a time of transition as more traditional approaches to law enforcement appear to be shifting toward those prioritizing prevention and diversion. Widespread adoption of naloxone administration by law enforcement officers in NYS is a powerful example of the successful integration of a public health intervention into police work., (© 2023. The Author(s).)

Background Social media has been more widely used by urology residency programs since the COVID-19 pandemic. There are no studies on the relationship between Doximity residency ranking and social media usage in urology. Objectives In this study, we aim to investigate the relationship between social media usage and the academic prestige of urology residency programs. Methods Residency reputation data was acquired from the Doximity Residency Navigator website. Twitter and Instagram activity in 2019 and 2021 was analyzed by collecting data on the total number of posts and followers. Data on residency virtual recruitment was obtained from Twitter and UroResidency website. Results By the end of 2021, 122/139 (87.8%) urology residency programs had a Twitter account and 61/139 (43.9%) had an Instagram account. A significant linear regression was found between Doximity ranking and the number of Twitter followers (p<0.001), Twitter posts (p=0.005), and Instagram followers (p=0.026). Virtual recruitment events were held by 107/139 (77%) programs in 2021. There was a significant linear regression between Doximity rankings and the number of virtual events (p<0.006). Conclusions Social media use by urology residency programs has increased since the COVID-19 pandemic. A program's higher Doximity ranking was correlated with the presence of Twitter and Instagram accounts as well as the number of Twitter followers, Twitter posts, and Instagram followers. There was a significant relationship between Doximity rankings and the number of hosted virtual events. Programs should consider increasing social media visibility to potentially improve their Doximity rankings., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Leung et al.)

Background: The COVID-19 pandemic has amplified the need for wide deployment of effective harm reduction strategies in preventing opioid overdose mortality. Placing naloxone in the hands of key responders, including law enforcement officers who are often first on the scene of a suspected overdose, is one such strategy. New York State (NYS) was one of the first states to implement a statewide law enforcement naloxone administration program. This article provides an overview of the law enforcement administration of naloxone in NYS between 2015 and 2020 and highlights key characteristics of over 9000 opioid overdose reversal events., Methods: Data in naloxone usage report forms completed by police officers were compiled and analyzed. Data included 9133 naloxone administration reports by 5835 unique officers located in 60 counties across NYS. Descriptive statistics were used to examine attributes of the aided individuals, including differences between fatal and non-fatal incidents. Additional descriptive analyses were conducted for incidents in which law enforcement officers arrived first at the scene of suspected overdose. Comparisons were made to examine year-over-year trends in administration as naloxone formulations were changed. Quantitative analysis was supplemented by content analysis of officers' notes (n = 2192)., Results: In 85.9% of cases, law enforcement officers arrived at the scene of a suspected overdose prior to emergency medical services (EMS) personnel. These officers assessed the likelihood of an opioid overdose having occurred based on the aided person's breathing status and other information obtained on the scene. They administered an average of 2 doses of naloxone to aided individuals. In 36.8% of cases, they reported additional administration of naloxone by other responders including EMS, fire departments, and laypersons. Data indicated the aided survived the suspected overdose in 87.4% of cases., Conclusions: With appropriate training, law enforcement personnel were able to recognize opioid overdoses and prevent fatalities by administering naloxone and carrying out time-sensitive medical interventions. These officers provided life-saving services to aided individuals alongside other responders including EMS, fire departments, and bystanders. Further expansion of law enforcement naloxone administration nationally and internationally could help decrease opioid overdose mortality., (© 2022. The Author(s).)

Context: Although viral suppression rates have recently increased among people with HIV, specific populations still experience disparities in health outcomes, a priority in the national response to end the HIV epidemic., Purpose: The end+disparities ECHO Collaborative, a quality improvement initiative among HIV providers in the United States from June 2018 to December 2019, created virtual communities of practice to measurably increase viral suppression rates in populations disproportionately affected by HIV: men who have sex with men of color, Black/African American and Latina women, youth aged 13 to 24 years, and transgender people., Methods: Participating Ryan White HIV/AIDS Program-funded providers prioritized their improvement efforts to focus on one target population and joined virtual affinity sessions with other providers focused on that population for guidance by subject matter experts and exchanges with peer providers. During 9 submission cycles, providers reported their viral suppression data for the preceding 12 months., Main Outcome Measures: The principal outcome measures were changes in viral suppression rates among 4 target populations and changes in viral suppression gaps compared with the rest of HIV-infected patients served by the same agency., Results: A total of 90 providers were included in the data analyses with an average of 110 775 reported patients, out of which 19 442 represented the targeted populations. The average viral suppression rates for agency-selected populations increased from 79.2% to 82.3% (a 3.9% increase), while the remaining caseload increased at a lower rate from 84.9% to 86.1% (a 1.4% increase). The viral suppression gap was reduced from 5.7% to 3.8%, a 33.5% reduction. Improvements were found across all target populations., Conclusions: The collaborative demonstrated improved health outcomes and reductions in HIV-related health disparities, moving toward ending the HIV epidemic. The model of utilizing low-cost videoconferencing technologies to create virtual communities of learning is well suited to mitigate other disease-related disparities, nationally and abroad., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Context: Gay, bisexual, and men who have sex with men (MSM) are disproportionately affected by the HIV/AIDS epidemic more than any other group. In New York State (NYS) outside of New York City (NYC), MSM accounted for 57% of new HIV/AIDS diagnoses in 2017. HIV/AIDS home testing initiatives have been effective at getting priority populations tested for HIV., Objectives: The NYS Department of Health (NYSDOH) administered the HIV Home Test Giveaway (HHTG) program through social media and mobile applications popular among the priority populations to (1) promote HIV screening among gay and bisexual men, MSM, transgender (TG), and gender queer/gender nonconforming (GNC) individuals who have sex with men, and (2) identify individuals with undiagnosed HIV infection., Design/setting: The NYSDOH recruited participants from NYS (excluding NYC) through social media campaigns between November 2016 and January 2018. Interested individuals were directed to an online eligibility survey. Eligible participants received a coupon via e-mail for a free HIV self-test (HIVST) kit through the manufacturer's Web site. Eligible participants received a $20 to $25 Amazon online gift card if they completed a voluntary online follow-up survey regarding their test results, experiences with the HHTG, and HIV/AIDS risk behaviors. Participants were also able to request assistance from the NYSDOH with further testing and various prevention and supportive services., Participants: In total, 6190 individuals participated and 3197 (52%) were eligible and received a coupon. Of the eligible, 2022 (63%) redeemed coupons for HIVST., Results: Among eligible participants, 976 (31%) reported having never been tested for HIV. On the follow-up survey, 922 (29%) participants reported having used the HIVST kit for themselves; 203 (22%) were first-time testers; and 7 (0.8%) tested HIV reactive. Of the follow-up survey participants, 761 (59%) requested assistance with various services., Conclusions: Media campaigns were effective in promoting HIV testing among priority populations and reaching individuals who have never been tested for HIV., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc.)

Prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) is known to cause renal papillary necrosis and, in rare cases, can cause sloughing of renal papillae with subsequent ureteral obstruction. We report the first documented case of an adult patient presenting with bilateral ureteral obstructions, secondary to bilateral papillary necrosis from chronic NSAID use. He subsequently underwent bilateral ureteral stent placement with rapid recovery of renal function., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Leung et al.)

Importance: New York State has been an epicenter for both the US coronavirus disease 2019 (COVID-19) and HIV/AIDS epidemics. Persons living with diagnosed HIV may be more prone to COVID-19 infection and severe outcomes, yet few studies have assessed this possibility at a population level., Objective: To evaluate the association between HIV diagnosis and COVID-19 diagnosis, hospitalization, and in-hospital death in New York State., Design, Setting, and Participants: This cohort study, conducted in New York State, including New York City, between March 1 and June 15, 2020, matched data from HIV surveillance, COVID-19 laboratory-confirmed diagnoses, and hospitalization databases to provide a full population-level comparison of COVID-19 outcomes between persons living with diagnosed HIV and persons living without diagnosed HIV., Exposures: Diagnosis of HIV infection through December 31, 2019., Main Outcomes and Measures: The main outcomes were COVID-19 diagnosis, hospitalization, and in-hospital death. COVID-19 diagnoses, hospitalizations, and in-hospital death rates comparing persons living with diagnosed HIV with persons living without dianosed HIV were computed, with unadjusted rate ratios and indirect standardized rate ratios (sRR), adjusting for sex, age, and region. Adjusted rate ratios (aRRs) for outcomes specific to persons living with diagnosed HIV were assessed by age, sex, region, race/ethnicity, transmission risk, and CD4+ T-cell count-defined HIV disease stage, using Poisson regression models., Results: A total of 2988 persons living with diagnosed HIV (2109 men [70.6%]; 2409 living in New York City [80.6%]; mean [SD] age, 54.0 [13.3] years) received a diagnosis of COVID-19. Of these persons living with diagnosed HIV, 896 were hospitalized and 207 died in the hospital through June 15, 2020. After standardization, persons living with diagnosed HIV and persons living without diagnosed HIV had similar diagnosis rates (sRR, 0.94 [95% CI, 0.91-0.97]), but persons living with diagnosed HIV were hospitalized more than persons living without diagnosed HIV, per population (sRR, 1.38 [95% CI, 1.29-1.47]) and among those diagnosed (sRR, 1.47 [95% CI, 1.37-1.56]). Elevated mortality among persons living with diagnosed HIV was observed per population (sRR, 1.23 [95% CI, 1.07-1.40]) and among those diagnosed (sRR, 1.30 [95% CI, 1.13-1.48]) but not among those hospitalized (sRR, 0.96 [95% CI, 0.83-1.09]). Among persons living with diagnosed HIV, non-Hispanic Black individuals (aRR, 1.59 [95% CI, 1.40-1.81]) and Hispanic individuals (aRR, 2.08 [95% CI, 1.83-2.37]) were more likely to receive a diagnosis of COVID-19 than White individuals, but they were not more likely to be hospitalized once they received a diagnosis or to die once hospitalized. Hospitalization risk increased with disease progression to HIV stage 2 (aRR, 1.29 [95% CI, 1.11-1.49]) and stage 3 (aRR, 1.69 [95% CI, 1.38-2.07]) relative to stage 1., Conclusions and Relevance: In this cohort study, persons living with diagnosed HIV experienced poorer COVID-related outcomes relative to persons living without diagnosed HIV; Previous HIV diagnosis was associated with higher rates of severe disease requiring hospitalization, and hospitalization risk increased with progression of HIV disease stage.

Background: New York State (NYS) has been an epicenter for both COVID-19 and HIV/AIDS epidemics. Persons Living with diagnosed HIV (PLWDH) may be more prone to COVID-19 infection and severe outcomes, yet few population-based studies have assessed the extent to which PLWDH are diagnosed, hospitalized, and have died with COVID-19, relative to non-PLWDH., Methods: NYS HIV surveillance, COVID-19 laboratory confirmed diagnoses, and hospitalization databases were matched. COVID-19 diagnoses, hospitalization, and in-hospital death rates comparing PLWDH to non-PLWDH were computed, with unadjusted rate ratios (RR) and indirect standardized RR (sRR), adjusting for sex, age, and region. Adjusted RR (aRR) for outcomes among PLWDH were assessed by age/CD4-defined HIV disease stage, and viral load suppression, using Poisson regression models., Results: From March 1-June 7, 2020, PLWDH were more frequently diagnosed with COVID-19 than non-PLWDH in unadjusted (RR [95% confidence interval (CI)]: 1.43[1.38-1.48), 2,988 PLWDH], but not in adjusted comparisons (sRR [95% CI]: 0.94[0.91-0.97]). Per-population COVID-19 hospitalization was higher among PLWDH (RR [95% CI]: 2.61[2.45-2.79], sRR [95% CI]: 1.38[1.29-1.47], 896 PLWDH), as was in-hospital death (RR [95% CI]: 2.55[2.22-2.93], sRR [95%CI]: 1.23 [1.07-1.40], 207 PLWDH), albeit not among those hospitalized (sRR [95% CI]: 0.96[0.83-1.09]). Among PLWDH, hospitalization risk increased with disease progression from HIV Stage 1 to Stage 2 (aRR [95% CI]:1.27[1.09-1.47]) and Stage 3 (aRR [95% CI]: 1.54[1.24-1.91]), and for those virally unsuppressed (aRR [95% CI]: 1.54[1.24-1.91])., Conclusion: PLWDH experienced poorer COVID-related outcomes relative to non-PLWDH, with 1-in-522 PLWDH dying with COVID-19, seemingly driven by higher rates of severe disease requiring hospitalization.

While primary care providers in New York State (NYS) are mandated to offer all patients a HIV test, still many NYS residents miss the HIV screening opportunity. To fill the gap, and as the CDC recommends, this study aimed to examine the feasibility of implementing HIV screening in dental setting, identify patient characteristics associated with acceptance of HIV rapid testing, and discuss best practices of HIV screening in dental setting. New York State Department of Health (NYSDOH) collaborated with the Northeast/Caribbean AIDS Education and Training Center (NECA AETC) and three dental schools in New York State to offer free HIV screening tests as a component of routine dental care between February 2016 and March 2018. Ten clinics in upstate New York and Long Island participated in the study. HIV screening was performed using the OraQuick™ In-Home HIV Test. 14,887 dental patients were offered HIV screening tests; 9,057 (60.8%) were screened; and one patient (0.011%) was confirmed HIV positive and linked to medical care. Of all dental patients, 33% had never been screened for HIV; and 56% had not had a primary care visit or had not been offered an HIV screening test by primary care providers in the previous 12 months. Multi-level generalized linear modeling analysis indicated that test acceptance was significantly associated with patient's age, race/ethnicity, gender, country of origin, primary payer (or insurance), past primary care visits, past HIV testing experiences, and the poverty level of patient's community. HIV screening is well accepted by dental patients and can be effectively integrated into routine dental care. HIV screening in the dental setting can be a good option for first-time testers, those who have not seen a primary care provider in the last 12 months, and those who have not been offered HIV screening at their last primary care visit., Competing Interests: The authors have declared that no competing interests exist.

Research has shown that pre-exposure prophylaxis (PrEP) is effective for preventing HIV infection. We developed the Targeted PrEP Implementation Program (TPIP), an 18-month project that involved five statewide agencies, to assess the extent to which PrEP could be implemented in "real world" clinical settings. The target population was men who have sex with men at high risk for HIV infection. Data were collected from a variety of sources. Implementing PrEP statewide required facilitating provider capacity, developing resources, and identifying/addressing potential barriers. TPIP focused on three key questions: (a) Can providers identify and retain appropriate candidates for PrEP? (b) Can PrEP participants adhere to daily medication? (c) Can PrEP be delivered as part of a comprehensive/integrated plan? There were 171 participating clients, most of whom successfully incorporated PrEP into their daily routines. After addressing initial barriers, we found that PrEP could be routinely delivered as part of a comprehensive prevention plan., (Copyright © 2017 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.)

Approximately 75% of all hepatitis C virus (HCV) infections in the United States and 73% of HCV-associated mortality occur in persons born during 1945-1965, placing this birth cohort at increased risk for liver cancer and other HCV-related liver disease (1). In the United States, an estimated 2.7 million persons are living with HCV infection, and it is estimated that up to 75% of these persons do not know their status. Since 2012, CDC has recommended that persons born during 1945-1965 receive one-time HCV testing. To increase the number of persons tested for HCV and to ensure timely diagnosis and linkage to care, in 2014, New York enacted a hepatitis C testing law that requires health care providers to offer HCV antibody screening to all persons born during 1945-1965 who are receiving services in primary care settings or as hospital inpatients, and to refer persons with positive HCV antibody tests for follow-up health care, including an HCV diagnostic test (i.e., HCV RNA).* The New York State Department of Health (NYSDOH) used survey data from clinical laboratories and Medicaid claims and encounter data, and state and New York City (NYC) HCV surveillance data to assess the number of persons tested for HCV and number of persons with newly diagnosed HCV infections who were linked to care. During the first year of the HCV law implementation, there was a 51% increase in specimens submitted for HCV testing to surveyed clinical laboratories; testing rates among active Medicaid clients increased 52%, and linkage to care among persons with newly diagnosed HCV infection increased approximately 40% in New York and 11% in NYC. These findings highlight the potential for state laws to promote HCV testing and the utility of HCV surveillance and Medicaid claims data to monitor the quality of HCV testing and linkage to care for HCV-infected persons.

Background and Objective: Development of miniaturized imaging systems with molecular probes enables examination of molecular changes leading to initiation and progression of colorectal cancer in an azoxymethane (AOM)-induced mouse model of the disease. Through improved and novel studies of animal disease models, more effective diagnostic and treatment strategies may be developed for clinical translation. We introduce use of a miniaturized multimodal endoscope with lavage-delivered fluorescent probes to examine dynamic microenvironment changes in an AOM-treated mouse model., Study Design/materials and Methods: The endoscope is equipped with optical coherence tomography (OCT) and laser induced fluorescence (LIF) imaging modalities. It is used with Cy5.5-conjugated antibodies to create time-resolved molecular maps of colon carcinogenesis. We monitored in vivo changes in molecular expression over a five month period for four biomarkers: epithelial growth factor receptor (EGFR), transferrin receptor (TfR), transforming growth factor beta 1 (TGFβ1), and chemokine (C-X-C motif) receptor 2 (CXCR2). In vivo OCT and LIF images were compared over multiple time points to correlate increases in biomarker expression with adenoma development., Results: This system is uniquely capable of tracking in vivo changes in molecular expression over time. Increased expression of the biomarker panel corresponded to sites of disease and offered predictive utility in highlighting sites of disease prior to detectable structural changes. Biomarker expression also tended to increase with higher tumor burden and growth rate in the colon., Conclusion: We can use miniaturized dual modality endoscopes with fluorescent probes to study the tumor microenvironment in developmental animal models of cancer and supplement findings from biopsy and tissue harvesting., (© 2014 Wiley Periodicals, Inc.)

Background and Objective: We utilize a miniature, dual-modality endoscope that combines fluorescence-based surface magnifying chromoendoscopy (SMC) and optical coherence tomography (OCT) to follow the anatomical changes that occur during adenoma development in the mouse colon., Materials and Methods: Twenty-five mice were treated with the carcinogen azoxymethane (AOM) to induce tumor development in the distal colon, or were treated with saline as control, and were imaged over six months. OCT detects adenoma number with high sensitivity and specificity and can measure lesion size. In methylene blue-lavaged colons, SMC detects changes in the colonic crypts. SMC images of control mouse colons exhibit reticulated patterns of crypts of equal size, forming either a dot or honeycomb pattern., Results: Images of AOM-treated colons show mild crypt irregularities even in grossly normal tissue. Images of small to medium adenoma exhibit larger crypts, more intense signal, and irregular spacing whereas those of large adenoma have heterogeneous, intense signal and loss of crypt structure., Conclusions: The combination of OCT and SMC permits the detection of neoplastic events from the earliest stages of crypt irregularities before gross tissue changes are noted, through to measuring the growth of protruding adenoma., (© 2014 Wiley Periodicals, Inc.)

Gold-coated liposomes are maneuvered using an optical trap to achieve precise delivery of encapsulated molecular cargo. Movement and payload release from these plasmon resonant nanocapsules are independently controlled using a pulsed trapping beam. This technology enables in vitro delivery of a payload to a selected cell and may be applied to the interrogation of individual cells within their biological microenvironment., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Technological limitations have prevented the interrogation and manipulation of cellular activity in response to bioactive molecules within model and living systems that is required for the development of diagnostic and treatment modalities for diseases, such as cancer. In this work, we demonstrate that gold-coated liposomes are capable of encapsulation and on-demand release of signaling molecules with a spatial and temporal resolution leading to activation of individual cells. As a model system, we used cells modified to overexpress a certain G-protein coupled receptor, the CCK2 receptor, and achieved its activation in a single cell via the localized release of its agonist. This content release was triggered by illumination of the liposomes at wavelengths corresponding to the plasmon resonance of the gold coating. The use of plasmon resonant liposomes may enable on-demand release of a broad range of molecules using biologically safe near-infrared light and without molecule chemical modification. In combination with the spectral tunability of plasmon resonant coating, this technology may allow for multiplexed interrogation of complex and diverse signaling pathways in model or living tissues with unprecedented spatial and temporal control.

Successful integration of diagnostic and therapeutic actions at the level of individual cells requires new materials that combine biological compatibility with functional versatility. This review focuses on the development of liposome-based functional materials, where payload release is activated by light. Methods of sensitizing liposomes to light have progressed from the use of organic molecular moieties to the use of metallic plasmon resonant structures. This development has facilitated application of near infrared light for activation, which is preferred for its deep penetration and low phototoxicity in biological tissues. Presented mechanisms of light-activated liposomal content release enable precise in vitro manipulation of minute amounts of reagents, but their use in clinical diagnostic and therapeutic applications will require demonstration of safety and efficacy.

Biodegradable, spectrally tunable plasmon resonant nanocapsules are created via the deposition of gold onto the surface of 100 nm diameter thermosensitive liposomes. These nanocapsules demonstrate selective release of encapsulated contents upon illumination with light of a wavelength matching their distinct resonance bands, which correspond to 760 and 1210 nm in this study. Spectrally selective release is accomplished through the use of multiple, low intensity laser pulses delivered over a period of less than four minutes, ensuring that illumination affects only the gold-coated liposomes and avoids heating the surrounding media. The result of this illumination scheme for selective release using multiple wavelengths of light is a biologically safe mechanism for realizing drug delivery, microfluidic, and sensor applications.

We recently demonstrated that liposome-supported plasmon resonant gold nanoshells are degradable into components of a size compatible with renal clearance, potentially enabling their use as multifunctional agents in applications in nanomedicine, including imaging, diagnostics, therapy, and drug delivery (Troutman et al., Adv. Mater. 2008, 20, 2604-2608). When illuminated with laser light at the wavelength matching their plasmon resonance band, gold-coated liposomes rapidly release their encapsulated substances, which can include therapeutic and diagnostic agents. The present research demonstrates that release of encapsulated agents from gold-coated liposomes can be spectrally controlled by varying the location of the plasmon resonance band; this spectral tuning is accomplished by varying the concentration of gold deposited on the surface of liposomes. Furthermore, the amount of laser energy required for release is qualitatively explained using the concept of thermal confinement (Jacques, Appl. Opt. 1993, 32(3), 2447-2454). Overlapping thermal confinement zones can be avoided by minimizing the laser pulse width, resulting in lower energy requirements for liposomal content release and less global heating of the sample. Control of heating is especially important in drug delivery applications, where it enables spatial and spectral control of delivery and prevents thermal damage to tissue.

We have recently introduced liposome-supported plasmon resonant gold nanoshells (Troutman et al., Adv. Mater. 2008, 20, 2604-2608). These plasmon resonant gold-coated liposomes are degradable into components of a size compatible with renal clearance, potentially enabling their use as multifunctional agents in applications in nanomedicine, including imaging, diagnostics, therapy, and drug delivery. The present research demonstrates that laser illumination at the wavelength matching the plasmon resonance band of a gold-coated liposome leads to the rapid release of encapsulated substances, which can include therapeutic and diagnostic agents. Leakage of encapsulated contents is monitored through the release of self-quenched fluorescein, which provides an increase in fluorescence emission upon release. Moreover, the resonant peak of these gold-coated liposomes is spectrally tunable in the near infrared range by varying the concentration of gold deposited on the surface of liposomes. Varying the plasmon resonant wavelengths of gold-coated liposomes can provide a method for spectrally-coding their light-mediated content release, so that the release event is initiated by the specific wavelength of light used to illuminate the liposomes. The development of spectrally-coded release can find applications in controlled delivery of multiple agents to support complex diagnostic tests and therapeutic interventions.