Nanotheranostics最新文献

{"title":"Longitudinal NMR Based Serum Metabolomics to Track the Potential Serum Biomarkers of Septic Shock.","authors":"Swarnima Pandey,&nbsp;Afzal Azim,&nbsp;Neeraj Sinha","doi":"10.7150/ntno.79394","DOIUrl":"https://doi.org/10.7150/ntno.79394","url":null,"abstract":"<p><p><b>Background:</b> Septic shock, with a prolonged hospital stay, has the highest mortality rate worldwide. There is a need for better management of the disease, which requires time-dependent analysis of alteration occurring in the disease condition and subsequent planning of treatment strategies to curb mortality. <b>Objective:</b> The study aims to identify early metabolic signatures associated with septic shock before treatment and post-treatment. It also entails the progression of patients towards recovery, which clinicians could use to analyze treatment efficacy. <b>Methods:</b> The study was performed on 157 serum samples of patients with septic shock. We performed metabolomic, univariate, and multivariate statistics to identify the significant metabolite signature of patients prior to treatment and during treatment by collecting serum samples on the day I, day III, and day V of treatment. <b>Results:</b> We identified metabotypes of patients before treatment and post-treatment. The study showed time-dependent metabolite alteration in ketone bodies, amino acids, choline, and NAG in patients undergoing treatment. <b>Conclusion:</b> This study illustrates the metabolite's journey in septic shock and during treatment, which may be of prospective assistance to clinicians to monitor therapeutics.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"7 2","pages":"142-151"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10842963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-resolution synchrotron K-edge subtraction CT allows tracking and quantifying therapeutic cells and their scaffold in a rat model of focal cerebral injury and can serve as a reference for spectral photon counting CT.","authors":"Clément Tavakoli,&nbsp;Elisa Cuccione,&nbsp;Chloé Dumot,&nbsp;Joëlle Balegamire,&nbsp;Salim Aymeric Si-Mohamed,&nbsp;Johoon Kim,&nbsp;Claire Crola-da-Silva,&nbsp;Yves Chevalier,&nbsp;Loïc Boussel,&nbsp;Philippe Douek,&nbsp;David Cormode,&nbsp;Hélène Elleaume,&nbsp;Emmanuel Brun,&nbsp;Marlène Wiart","doi":"10.7150/ntno.79575","DOIUrl":"https://doi.org/10.7150/ntno.79575","url":null,"abstract":"<p><p><b>Background:</b> The objective of this study was to demonstrate that synchrotron K-edge subtraction tomography (SKES-CT) can simultaneously track therapeutic cells and their encapsulating carrier, <i>in vivo,</i> in a rat model of focal brain injury using a dual-contrast agent approach. The second objective was to determine if SKES-CT could be used as a reference method for spectral photon counting tomography (SPCCT). <b>Methods:</b> Phantoms containing different concentrations of gold and iodine nanoparticles (AuNPS/INPs) were imaged with SKES-CT and SPCCT to assess their performances. A pre-clinical study was performed in rats with focal cerebral injury which intracerebrally received AuNPs-labelled therapeutic cells encapsulated in a INPs-labelled scaffold. Animals were imaged <i>in vivo</i> with SKES-CT and back-to-back with SPCCT. <b>Results:</b> SKES-CT revealed to be reliable for quantification of gold and iodine, whether alone or mixed. In the preclinical model, SKES-CT showed that AuNPs remained at the site of cell injection, while INPs expanded within and/or along the lesion border, suggesting dissociation of both components in the first days post-administration. Compared to SKES-CT, SPCCT was able to correctly locate gold, but not completely located iodine. When SKES-CT was used as reference, SPCCT gold quantification appeared very accurate both <i>in vitro</i> and <i>in vivo</i>. Iodine quantification by SPCCT was also quite accurate, albeit less so than for gold. <b>Conclusion:</b> We here provide the proof-of-concept that SKES-CT is a novel method of choice for performing dual-contrast agent imaging in the context of brain regenerative therapy. SKES-CT may also serve as ground truth for emerging technologies such as multicolour clinical SPCCT.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"7 2","pages":"176-186"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10842960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gold Nanoparticles Conjugated with Dendrigraft Poly-L-lysine and Folate-Targeted Poly(ethylene glycol) for siRNA Delivery to Prostate cancer.","authors":"Georges Minassian,&nbsp;Esther Ghanem,&nbsp;Roland El Hage,&nbsp;Kamil Rahme","doi":"10.7150/ntno.79050","DOIUrl":"https://doi.org/10.7150/ntno.79050","url":null,"abstract":"<p><p>Dendrigraft Poly-L-Lysine (d-PLL) coated gold nanoparticles (AuNPs) were synthesized by reducing Tetrachloroauric acid with ascorbic acid in the presence of d-PLL. AuNPs-d-PLL formed a stable colloidal solution that absorbs light at a maximum wavelength (λ_max) centered at 570 nm as demonstrated by UV-visible (UV-Vis) spectroscopy. From Scanning Electron Microscopy (SEM) analysis, AuNPs-d-PLL were spherical in shape with a mean diameter of 128 ± 47 nm. Dynamic Light scattering (DLS) analysis of the colloidal solution exhibited one size distribution with a hydrodynamic diameter of about 131 nm (size distribution by intensity). Zeta potential (ξ) measurements revealed positively charged AuNPs-d-PLL with ξ about 32 mV, an indicator of high stability in an aqueous solution. The AuNPs-d-PLL was successfully modified with either thiolated poly (ethylene glycol) SH-PEG-OCH₃ (M_w 5400 g mol^-1) or folic acid-modified thiolated poly (ethylene glycol) SH-PEG-FA of similar molecular weight as demonstrated via DLS and Zeta potential measurements. Complexation of PEGylated AuNPs-d-PLL with siRNA was confirmed by DLS and gel electrophoresis. Finally, we analyzed the functionalization of our nanocomplexes with folic acid via targeted cellular uptake to prostate cancer cells using flow cytometry and LSM imaging. Our findings implicate the broader applicability of folate-PEGylated AuNPs in siRNA-based therapeutics against prostate cancer and perhaps other types of cancer.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"7 2","pages":"152-166"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10851677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized biosensors for point-of-care diagnostics: from bench to bedside applications.","authors":"Pranjal Chandra","doi":"10.7150/ntno.81485","DOIUrl":"https://doi.org/10.7150/ntno.81485","url":null,"abstract":"<p><p>The most significant feature of translational point-of-care technology \"Personalized biosensors\" is that it can be done quickly and by clinical staff who are not trained in clinical laboratory sciences. Rapid test results can quickly give a doctor or other medical worker answers that can help them decide what to do or how to treat a patient. This is helpful almost everywhere, from the emergency room to a patient getting care at home. When a doctor meets a patient for the first time, during a flare-up of a known problem or when a new symptom shows up in a patient who is already being treated, having faster access to test results gives the doctor answers when they are with the patient or are about to see the patient which indicate the importance of point-of-care technologies and their future scope.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"7 2","pages":"210-215"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10851679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin Nanofiber PCL/PLGA/Collagen Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cells against Liver Fibrosis in Animal Model and Prevented its Recurrence.","authors":"Gehan Abd-Elfatah Tawfeek,&nbsp;Hend Ahmed Kasem,&nbsp;Sherif Elsayed Elshoala","doi":"10.7150/ntno.81019","DOIUrl":"https://doi.org/10.7150/ntno.81019","url":null,"abstract":"<p><p>The aim of this study is preconditioning of hBM-MSCs using curcumin modified nanomembrane to optimize therapy of hepatic fibrosis and preventing its recurrence. <b>Methods:</b> The nanomembrane was prepared by electrospinning technique and characterized using conventional method (cur^- nanoscaffold and cur⁺ nanoscaffold). Kinetic release of curcumin was also measured by spectrophotometry. MSCs were isolated from human bone marrow (hBM-MSCs) and cultured on the both nanoscaffolds. We evaluated the <i>in-vivo</i> effect of hBM-MSCs from both nanoscaffold cultures (cur^- nanoscaffold/hMSCs and cur⁺ nanoscaffold/MSCs) on liver fibrosis from its effective and preventive points and we assessed the mechanisms of these effects as <i>in vitro</i> studies as cell proliferation, its effect on hepatogenic differentiation, its effect on paracrine release of hBM-MSCs and <i>in-vivo</i> studying the effect on cell migration, survival, engraftment, fate of transplanted cells, modifying the fibrogenic and inflammatory microenvironments. <b>Results:</b> The results of animal model showed that single injection of preconditioning of hBM-MSCs using curcumin modified nanoscaffold ameliorate the fibrosis and prevent its recurrence until 24 weeks of therapy in contrast to improvement but not ameliorative effect of hBM-MSCs/ curcumin negative nanoscaffold which recurred progressively after 12 weeks of therapy. These effects of curcumin modified nanoscaffold were results from its highly efficacy on cell proliferation, <i>in-vitro</i> and <i>in-vivo</i> hepatogenic differentiation, increasing cell migration, engraftment and survival in the inflammatory microenvironment which was markedly improved by down regulation of inflammatory mediators and upregulation of anti-oxidant factors. <b>Conclusion:</b> hBM-MSCs cultured on the prepared curcumin nanomembrane in this study is promising in regenerative therapy for ameliorating the hepatic fibrosis and to prevent its recurrence.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"7 3","pages":"299-315"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9386898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative effects of free doxorubicin, liposome encapsulated doxorubicin and liposome co-encapsulated alendronate and doxorubicin (PLAD) on the tumor immunologic milieu in a mouse fibrosarcoma model.","authors":"Md Rakibul Islam,&nbsp;Jalpa Patel,&nbsp;Patricia Ines Back,&nbsp;Hilary Shmeeda,&nbsp;Konstantin Adamsky,&nbsp;Hui Yang,&nbsp;Carlos Alvarez,&nbsp;Alberto A Gabizon,&nbsp;Ninh M La-Beck","doi":"10.7150/ntno.75045","DOIUrl":"https://doi.org/10.7150/ntno.75045","url":null,"abstract":"<p><p><b>Background:</b> We have previously shown that alendronate, an amino-bisphosphonate, when reformulated in liposomes, can significantly enhance the efficacy of cytotoxic chemotherapies and help remodel the immunosuppressive tumor microenvironment towards an immune-permissive milieu resulting in increased anticancer efficacy. In addition, we have previously shown that the strong metal-chelating properties of alendronate can be exploited for nuclear imaging of liposomal biodistribution. To further improve anticancer efficacy, a pegylated liposome formulation co-encapsulating alendronate and doxorubicin (PLAD) has been developed. In this study, we examined the effects of PLAD on the tumor immunologic milieu in a mouse fibrosarcoma model in which the tumor microenvironment is heavily infiltrated with tumor-associated macrophages (TAM) that are associated with poor prognosis and treatment resistance. <b>Methods:</b> Doxorubicin biodistribution, characterization of the tumor immunologic milieu, cellular doxorubicin uptake, and tumor growth studies were performed in Balb/c mice bearing subcutaneously implanted WEHI-164 fibrosarcoma cells treated intravenously with PLAD, pegylated liposomal doxorubicin (PLD), free doxorubicin, or vehicle. <b>Results:</b> PLAD delivery resulted in a high level of tumor doxorubicin that was 20 to 30-fold greater than in free doxorubicin treated mice, and non-significantly higher than in PLD treated mice. PLAD also resulted in increased uptake in spleen and slightly lower plasma levels as compared to PLD. Importantly, our results showed that PLAD, and to a lesser extent PLD, shifted cellular drug uptake to TAM and to monocytic myeloid-derived suppressor cells (MDSC), while there was no drug uptake in neutrophilic MDSC or lymphoid cells. Free doxorubicin cellular drug uptake was below detectable levels. PLAD, and to a lesser extent PLD, also induced significant changes in number and functionality of tumor-infiltrating TAM, MDSC, Treg, NKT, and NK cells that are consistent with enhanced antitumor immune responses in the tumor microenvironment. In contrast, free doxorubicin induced moderate changes in the tumor microenvironment that could promote (decreased Treg) or be detrimental to antitumor immune responses (decreased M1 TAM and NK cells). These immune modulatory effects are reflected in the therapeutic study which showed that PLAD and PLD inhibited tumor growth and significantly prolonged survival, while free doxorubicin showed little or no anticancer activity. <b>Conclusion:</b> We show that liposomal delivery of doxorubicin not only alters pharmacokinetics, but also dramatically changes the immune modulatory activity of the drug cargo. In addition, our data support that the PLAD nanotheranostic platform further enhances some immune changes that may act in synergy with its cytotoxic chemotherapy effects.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":" ","pages":"451-464"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9461478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40358446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress on Applying Carbon Dots for Inhibition of RNA Virus Infection.","authors":"Yaung Kwee,&nbsp;Yiqun Zhou,&nbsp;Mochamad Zakki Fahmi,&nbsp;Madhuri Sharon,&nbsp;Alfinda Novi Kristanti","doi":"10.7150/ntno.73918","DOIUrl":"https://doi.org/10.7150/ntno.73918","url":null,"abstract":"<p><p>Viral infection is a globally leading health issue. Annually, new lethal RNA viruses unexpectedly emerged and mutated threatening health and safety. Meanwhile, it is urgent to explore novel antiviral agents, which, however, takes years to be clinically available. Nonetheless, the development of carbon dots (CDs) in the past 20 years has exhibited their vast application potentials and revealed their promising capacity as future antiviral agents considering their versatile properties and significant antiviral responses. Thus, CDs have been widely investigated as an alternative of traditional chemotherapy for inhibiting viral infection and replication <i>in vitro</i>. Meanwhile, attempts to apply CDs to <i>in vivo</i> systems are in high demand. In this review, recent developments of CDs-based antiviral therapies are systematically summarized. Furthermore, the role of CDs in photodynamic inactivation to kill viruses or bacteria is briefly discussed.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":" ","pages":"436-450"},"PeriodicalIF":0.0,"publicationDate":"2022-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40342714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stealth Liposomal Chemotherapeutic Agent for Triple Negative Breast Cancer with Improved Pharmacokinetics.","authors":"Nagavendra Kommineni, David Paul, Raju Saka, Wahid Khan, Satheeshkumar Nanjappan","doi":"10.7150/ntno.76370","DOIUrl":"10.7150/ntno.76370","url":null,"abstract":"<p><p>Triple-negative breast cancer is one of the most lethal cancers. Chemotherapeutics for targeting CDK4 and CDK6 like Palbociclib (PAB) in triple-negative breast cancer was widely explored. However, poor bioavailability and severe side effects profile limiting its clinical usage in the field of cancer chemotherapy. Herein, we set out to develop the stealth liposomes (LPS) of PAB by rotary thin film evaporation with a vesicle size of less than 100 nm. <i>In vitro,</i> drug release studies were performed and fitted into different release kinetic models. LPS were characterized by electron microscopic techniques for morphology. The engineered nanotherapeutics agents were further evaluated in 4T1 triple-negative breast cancer cell lines for its anti-cancer potential and cellular uptake. The hemolytic potential and pharmacokinetic (PK) behavior of developed LPS-PAB and PAB were analyzed by using robust UHPLC-QTOF-MS method. LPS-PAB demonstrates biphasic release profile with first-order release kinetics. Further, LPS-PAB has shown less IC₅₀ value (1.99 µM) compared to PAB alone (3.24 µM). The designed nanoliposomes were tagged with fluorescent FITC dye to check rapid cellular uptake. Importantly, stealth LPS-PAB has shown a 1.75-fold reduction in hemolytic potential as compared to PAB plain drug at 100 µg/mL concentration. The PK results obtained was displayed 2.5-fold increase in C_max, 1.45-fold increase in AUC_tot, 1.8-fold increase in half-life and 1.3-fold increase in MRT with LPS-PAB when compared to orally administered PAB suspension. These findings suggest that novel LPS-PAB can be employed as an alternate therapeutic strategy to eradicate triple-negative breast cancer.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":" ","pages":"424-435"},"PeriodicalIF":0.0,"publicationDate":"2022-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40342715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Covalent core-radiolabeling of polymeric micelles with ¹²⁵I/²¹¹At for theranostic radiotherapy.","authors":"Emanuel Sporer,&nbsp;Christian B M Poulie,&nbsp;Tom Bäck,&nbsp;Sture Lindegren,&nbsp;Holger Jensen,&nbsp;Paul J Kempen,&nbsp;Andreas Kjaer,&nbsp;Matthias M Herth,&nbsp;Andreas I Jensen","doi":"10.7150/ntno.71906","DOIUrl":"https://doi.org/10.7150/ntno.71906","url":null,"abstract":"Astatine-211 (211At) is one of the most promising α-emitters for targeted alpha therapy, especially of cancer metastases. However, the lack of a stable isotope, frequent in vivo deastatination, and limited radiochemical knowledge makes it challenging to apply. Here, we report a new strategy for radiolabeling the lipophilic core of polymeric micelles (PMs) with covalently bound 211At. The PMs were radiolabeled via either an indirect synthon-based method or directly on the amphipathic block copolymer. The radiochemistry was optimized with iodine-125 (125I) and then adapted for 211At, enabling the use of both elements as a potential theranostic pair. PMs that were core-radiolabeled with both 125I or 211At were prepared and characterized, based on a PEG(5k)-PLGA(10k) co-polymer. The stability of the radiolabeled PMs was evaluated in mouse serum for 21 h, showing radiochemical stability above 85%. After in vivo evaluation of the 211At- labeled PMs, 4-5 % ID/g of the 211At could still be detected in the blood, showing a promising in vivo stability of the PMs. Further, 211At-labeled PMs accumulated in the spleen (20-30 %ID/g) and the liver (2.5- 5.5 %ID/g), along with some detection of 211At in the thyroid (3.5-9 %ID/g). This led to the hypothesis that deastatination takes place in the liver, whereas good stability of the 211At core-radiolabel was observed in the blood.","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":" ","pages":"388-399"},"PeriodicalIF":0.0,"publicationDate":"2022-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40574976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-triggered oxygen-loaded nanodroplets enhance and monitor cerebral damage from sonodynamic therapy.","authors":"Harriet Lea-Banks,&nbsp;Sheng-Kai Wu,&nbsp;Hannah Lee,&nbsp;Kullervo Hynynen","doi":"10.7150/ntno.71946","DOIUrl":"https://doi.org/10.7150/ntno.71946","url":null,"abstract":"In sonodynamic therapy, cellular toxicity from sonosensitizer drugs, such as 5-aminolevulinic acid hydrochloride (5-ALA), may be triggered with focused ultrasound through the production of reactive oxygen species (ROS). Here we show that by increasing local oxygen during treatment, using oxygen-loaded perfluorocarbon nanodroplets (250 +/- 8 nm), we can increase the damage induced by 5-ALA, and monitor the severity by recording acoustic emissions in the brain. To achieve this, we sonicated the right striatum of 16 healthy rats after an intravenous dose of 5-ALA (200 mg/kg), followed by saline, nanodroplets, or oxygen-loaded nanodroplets. We assessed haemorrhage, edema and cell apoptosis immediately following, 24 hr, and 48 hr after focused ultrasound treatment. The localized volume of damaged tissue was significantly enhanced by the presence of oxygen-loaded nanodroplets, compared to ultrasound with unloaded nanodroplets (3-fold increase), and ultrasound alone (40-fold increase). Sonicating 1 hr following 5-ALA injection was found to be more potent than 2 hr following 5-ALA injection (2-fold increase), and the severity of tissue damage corresponded to the acoustic emissions from droplet vaporization. Enhancing the local damage from 5-ALA with monitored cavitation activity and additional oxygen could have significant implications in the treatment of atherosclerosis and non-invasive ablative surgeries.","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":" ","pages":"376-387"},"PeriodicalIF":0.0,"publicationDate":"2022-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40566080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}