Pub Date : 2021-06-11DOI: 10.1101/2021.06.10.447962
Chaemin Lim, Jacob D. Ramsey, Duhyeong Hwang, S. Teixeira, C. Poon, J. Strauss, E. Rosen, M. Sokolsky-Papkov, A. Kabanov
Significant advances in physicochemical properties of polymeric micelles enable optimization of therapeutic drug efficacy, supporting nanomedicine manufacturing and clinical translation. Yet, the effect of micelle morphology on pharmacological efficacy has not been adequately addressed. We addressed this gap by assessing pharmacological efficacy of polymeric micelles with spherical and worm-like morphologies. We observed that poly(2-oxazoline)-based polymeric micelles can be elongated over time from a spherical structure to worm-like structure, with elongation influenced by several conditions, including the amount and type of drug loaded into the micelles. We further evaluated the role of different morphologies of olaparib micelles on pharmacological performance against a triple-negative breast cancer tumor (TNBC) model. Spherical micelles accumulated rapidly in the tumor tissue while retaining large amounts of drug; worm-like micelles accumulated more slowly and only upon releasing significant amounts of drug. These findings suggest that the dynamic character of the drug–micelle structure and the micelle morphology play a critical role in pharmacological performance, and that spherical micelles are better suited for systemic delivery of anticancer drugs to tumors when drugs are loosely associated with the polymeric micelles.
{"title":"Drug-Dependent Morphological Transitions in Spherical and Worm-Like Polymeric Micelles Define Stability and Pharmacological Performance of Micellar Drugs","authors":"Chaemin Lim, Jacob D. Ramsey, Duhyeong Hwang, S. Teixeira, C. Poon, J. Strauss, E. Rosen, M. Sokolsky-Papkov, A. Kabanov","doi":"10.1101/2021.06.10.447962","DOIUrl":"https://doi.org/10.1101/2021.06.10.447962","url":null,"abstract":"Significant advances in physicochemical properties of polymeric micelles enable optimization of therapeutic drug efficacy, supporting nanomedicine manufacturing and clinical translation. Yet, the effect of micelle morphology on pharmacological efficacy has not been adequately addressed. We addressed this gap by assessing pharmacological efficacy of polymeric micelles with spherical and worm-like morphologies. We observed that poly(2-oxazoline)-based polymeric micelles can be elongated over time from a spherical structure to worm-like structure, with elongation influenced by several conditions, including the amount and type of drug loaded into the micelles. We further evaluated the role of different morphologies of olaparib micelles on pharmacological performance against a triple-negative breast cancer tumor (TNBC) model. Spherical micelles accumulated rapidly in the tumor tissue while retaining large amounts of drug; worm-like micelles accumulated more slowly and only upon releasing significant amounts of drug. These findings suggest that the dynamic character of the drug–micelle structure and the micelle morphology play a critical role in pharmacological performance, and that spherical micelles are better suited for systemic delivery of anticancer drugs to tumors when drugs are loosely associated with the polymeric micelles.","PeriodicalId":105333,"journal":{"name":"Small (Weinheim an Der Bergstrasse, Germany)","volume":"325 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121578573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-03-06DOI: 10.1101/2020.03.04.20029538
Ming Wang, Aisi Fu, Ben Hu, Y. Tong, Ran Liu, Zhen Liu, Jiashuang Gu, Bin Xiang, Jianghao Liu, Wen Jiang, Gaigai Shen, Wanxu Zhao, Dong Men, Z. Deng, Lilei Yu, Wu Wei, Yan Li, Tiangang Liu
The ongoing novel coronavirus pneumonia COVID-19 outbreak in Wuhan, China, has engendered numerous cases of infection and death. COVID-19 diagnosis relies upon nucleic acid detection; however, current recommended methods exhibit high false-negative rates, low sensitivity, and cannot identify other respiratory virus infections, thereby resulting patient misdiagnosis and impeding epidemic containment. Combining the advantages of target amplification and long-read, real-time nanopore sequencing, we developed nanopore target sequencing (NTS) to detect SARS-CoV-2 and other respiratory viruses simultaneously within 6-10 h. Parallel testing with approved qPCR kits of SARS-CoV-2 and NTS using 61 nucleic acid samples from suspected COVID-19 cases confirmed that NTS identified more infected patients as positive, and could also monitor for mutated nucleic acid sequence or other respiratory virus infection in the test sample. NTS is thus suitable for contemporary COVID-19 diagnosis; moreover, this platform can be further extended for diagnosing other viruses or pathogens.
{"title":"Nanopore Targeted Sequencing for the Accurate and Comprehensive Detection of SARS‐CoV‐2 and Other Respiratory Viruses","authors":"Ming Wang, Aisi Fu, Ben Hu, Y. Tong, Ran Liu, Zhen Liu, Jiashuang Gu, Bin Xiang, Jianghao Liu, Wen Jiang, Gaigai Shen, Wanxu Zhao, Dong Men, Z. Deng, Lilei Yu, Wu Wei, Yan Li, Tiangang Liu","doi":"10.1101/2020.03.04.20029538","DOIUrl":"https://doi.org/10.1101/2020.03.04.20029538","url":null,"abstract":"The ongoing novel coronavirus pneumonia COVID-19 outbreak in Wuhan, China, has engendered numerous cases of infection and death. COVID-19 diagnosis relies upon nucleic acid detection; however, current recommended methods exhibit high false-negative rates, low sensitivity, and cannot identify other respiratory virus infections, thereby resulting patient misdiagnosis and impeding epidemic containment. Combining the advantages of target amplification and long-read, real-time nanopore sequencing, we developed nanopore target sequencing (NTS) to detect SARS-CoV-2 and other respiratory viruses simultaneously within 6-10 h. Parallel testing with approved qPCR kits of SARS-CoV-2 and NTS using 61 nucleic acid samples from suspected COVID-19 cases confirmed that NTS identified more infected patients as positive, and could also monitor for mutated nucleic acid sequence or other respiratory virus infection in the test sample. NTS is thus suitable for contemporary COVID-19 diagnosis; moreover, this platform can be further extended for diagnosing other viruses or pathogens.","PeriodicalId":105333,"journal":{"name":"Small (Weinheim an Der Bergstrasse, Germany)","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130199764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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