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Tugba Yildiz,1 Renpeng Gu,2 Stefan Zauscher,2 Tania Betancourt1,3 1Materials Science, Engineering, and Commercialization Program, Texas State University, San Marcos, TX, 2Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 3Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX, USA Introduction: Despite significant progress in the field of oncology, cancer remains one of the leading causes of death. Chemotherapy is one of the most common treatment options for cancer patients but is well known to result in off-target toxicity. Theranostic nanomedicines that integrate diagnostic and therapeutic functions within an all-in-one platform can increase tumor selectivity for more effective chemotherapy and aid in diagnosis and monitoring of therapeutic responses. Material and methods: In this work, theranostic nanoparticles were synthesized with commonly used biocompatible and biodegradable polymers and used as cancer contrast and therapeutic agents for optical imaging and treatment of breast cancer. These core–shell nanoparticles were prepared by nanoprecipitation of blends of the biodegradable and biocompatible amphiphilic copolymers poly(lactic-co-glycolic acid)-b-poly-L-lysine and poly(lactic acid)-b-poly(ethylene glycol). Poly-L-lysine in the first copolymer was covalently decorated with near-infrared fluorescent Alexa Fluor 750 molecules. Results: The spherical nanoparticles had an average size of 60–80 nm. The chemotherapeutic drug doxorubicin was encapsulated in the core of nanoparticles at a loading of 3% (w:w) and controllably released over a period of 30 days. A 33-fold increase in near-infrared fluorescence, mediated by protease-mediated cleavage of the Alexa Fluor 750-labeled poly-L-lysine on the surface of the nanoparticles, was observed upon interaction with the model protease trypsin. The cytocompatibility of drug-free nanoparticles and growth inhibition of drug-loaded nanoparticles on MDA-MB-231 breast cancer cells were investigated with a luminescence cell-viability assay. Drug-free nanoparticles were found to cause minimal toxicity, even at high concentrations (0.2–2,000 µg/mL), while doxorubicin-loaded nanoparticles significantly reduced cell viability at drug concentrations >10 µM. Finally, the interaction of the nanoparticles with breast cancer cells was studied utilizing fluorescence microscopy, demonstrating the potential of the nanoparticles to act as near-infrared fluorescence optical imaging agents and drug-delivery carriers. Conclusion: Doxorubicin-loaded, enzymatically activatable nanoparticles of less than 100 nm were prepared successfully by nanoprecipitation of copolymer blends. These nanoparticles were found to be suitable as controlled drug delivery systems and contrast agents for imaging of cancer cells. Keywords: nanomedicine, theranostics, drug delivery, fluorescence imaging, enzymatic activation, nanoprecipitation, block copolymers, PLGA, PLA, PEG, poly-L-lysine, nanoparticles

Travis Cantu,1 Kyle Walsh,2 Varun P Pattani,3 Austin J Moy,3 James W Tunnell,3 Jennifer A Irvin,1,2 Tania Betancourt1,2 1Materials Science, Engineering, and Commercialization Program, Texas State University, San Marcos, TX, USA; 2Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX, USA; 3Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA Abstract: Laser-mediated photothermal ablation of cancer cells aided by photothermal agents is a promising strategy for localized, externally controlled cancer treatment. We report the synthesis, characterization, and in vitro evaluation of conductive polymeric nanoparticles (CPNPs) of poly(diethyl-4,4'-{[2,5-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-1,4-phenylene]bis(oxy)}dibutanoate) (P1) and poly(3,4-ethylenedioxythiophene) (PEDOT) stabilized with 4-dodecylbenzenesulfonic acid and poly(4-styrenesulfonic acid-co-maleic acid) as photothermal ablation agents. The nanoparticles were prepared by oxidative-emulsion polymerization, yielding stable aqueous suspensions of spherical particles of

© 2017 International Society for Traumatic Stress Studies.Most mental health services for trauma-exposed children and adolescents were not originally developed for refugees. Information is needed to help clinicians design services to address the consequences of trauma in refugee populations. We compared trauma exposure, psychological distress, and mental health service utilization among children and adolescents of refugee-origin, immigrant-origin, and U.S.-origin referred for assessment and treatment by U.S. providers in the National Child Traumatic Stress Network (NCTSN). We used propensity score matching to compare trauma profiles, mental health needs, and service use across three groups. Our sample comprised refugee-origin youth (n = 60, 48.3% female, mean age = 13.07 years) and propensity-matched samples of immigrant-origin youth (n = 143, 60.8% female, mean age = 13.26 years), and U.S.-origin youth (n = 140, 56.1% female, mean age = 12.11 years). On average, there were significantly more types of trauma exposure among refugee youth than either U.S.-origin youth (p < .001) or immigrant youth (p ≤ .001). Compared with U.S.-origin youth, refugee youth had higher rates of community violence exposure, dissociative symptoms, traumatic grief, somatization, and phobic disorder. In contrast, the refugee group had comparably lower rates of substance abuse and oppositional defiant disorder (ps ranging from .030 to < .001).This clinic-referred sample of refugee-origin youth presented with distinct patterns of trauma exposure, distress symptoms, and service needs that merit consideration in services planning.

The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk-derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen-containing compounds. The “promise” of a mollusk-derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk-derived anticancer agents and solutions to their procurement in quantity., SCOPUS: re.j, info:eu-repo/semantics/published

© 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc. Background and Objective Nanotechnology offers the possibility of creating multi-functional structures that can provide solutions for biomedical problems. The nanoprobes herein described are an example of such structures, where nano-scaled particles have been designed to provide high specificity and contrast potential for optical detection of cancer. Specifically, enzymatically activated fluorescent nanoprobes (EANPs) were synthesized as cancer-specific contrast agents for optical imaging. Study Design/Materials and Methods EANPs were prepared by nanoprecipitation of blends of poly(lactic acid)-b-poly(ethylene glycol) and poly(lactic-co-glycolic acid)-b-poly(l-lysine). The lysine moieties were then covalently decorated with the near infrared (NIR) fluorescent molecule AlexaFluor-750 (AF750). Close proximity of the fluorescent molecules to each other resulted in fluorescence quenching, which was reversed by enzymatically mediated cleavage of poly(l-lysine) chains. EANPs were characterized by dynamic light scattering and electron microscopy. Enzymatic development of fluorescence was studied in vitro by fluorescence spectroscopy. Biocompatibility and contrast potential of EANPs were studied in cancerous and noncancerous cells. The potential of the nanoprobes as contrast agents for NIR fluorescence imaging was studied in tissue phantoms. Results Spherical EANPs of ∼100 nm were synthesized via nanoprecipitation of polymer blends. Fluorescence activation of EANPs by treatment with a model protease was demonstrated with up to 15-fold optical signal enhancement within 120 minutes. Studies with MDA-MB-231 breast cancer cells demonstrated the cytocompatibility of EANPs, as well as enhanced fluorescence associated with enzymatic activation. Imaging studies in tissue phantoms confirmed the ability of a simple imaging system based on a laser source and CCD camera to image dilute suspensions of the nanoprobe at depths of up to 4 mm, as well as up to a 13-fold signal-to-background ratio for enzymatically activated EANPs compared to un-activated EANPs at the same concentration. Conclusion Nanoprecipitation of copolymer blends containing poly(l-lysine) was utilized as a method for preparation of highly functional nanoprobes with high potential as contrast agents for fluorescence based imaging of cancer. Lasers Surg. Med. 47:579-594, 2015.