作者机构:
[Liu, Zhenbao; Cai, Shundong; Chen, Jun; He, Qunye; Yan, Jianhua; Xiong, Hongjie] Cent South Univ, Xiangya Sch Pharmaceut Sci, Changsha 410013, Peoples R China.;[Mo, Miao] Cent South Univ, Xiangya Hosp, Dept Urol, Changsha 410008, Peoples R China.;[Liu, Yanfei] Cent South Univ, Sch Chem & Chem Engn, Changsha 410083, Peoples R China.;[Peng, Dongming] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.;[Mo, Miao; Liu, ZB] Cent South Univ, 172 Tongzipo Rd, Changsha 410013, Peoples R China.
通讯机构:
[Mo, M; Liu, ZB] C;Cent South Univ, 172 Tongzipo Rd, Changsha 410013, Peoples R China.
关键词:
Cancer therapy;Stimuli responsive;Dynamic targeting;Drug delivery system;Controlled release
摘要:
Conventional tumor-targeted drug delivery systems (DDSs) face challenges, such as unsatisfied systemic circulation, low targeting efficiency, poor tumoral penetration, and uncontrolled drug release. Recently, tumor cellular molecules-triggered DDSs have aroused great interests in addressing such dilemmas. With the introduction of several additional functionalities, the properties of these smart DDSs including size, surface charge and ligand exposure can response to different tumor microenvironments for a more efficient tumor targeting, and eventually achieve desired drug release for an optimized therapeutic efficiency. This review highlights the recent research progresses on smart tumor environment responsive drug delivery systems for targeted drug delivery. Dynamic targeting strategies and functional moieties sensitive to a variety of tumor cellular stimuli, including pH, glutathione, adenosine-triphosphate, reactive oxygen species, enzyme and inflammatory factors are summarized. Special emphasis of this review is placed on their responsive mechanisms, drug loading models, drawbacks and merits. Several typical multi-stimuli responsive DDSs are listed. And the main challenges and potential future development are discussed. (C) 2019 Shenyang Pharmaceutical University. Published by Elsevier B.V.
摘要:
Microglia are the most widely equipped protective cells in the brain and play a pivotal role in the development of neurological diseases. Inflammatory response and oxidative stress are critical risk factors in the activation of microglia which may cause various neurological diseases. Higenamine (Hig), a plant-based alkaloid and isolated from Aconite tuber, exhibits various properties and is mainly applied to treat heart failure. In addition, Hig expresses potential protective effects for neurodegenerative diseases. However, the effects and mechanisms of Hig on lipopolysaccharide (LPS) activated mouse microglia has not been fully explored. Therefore, we evaluated the anti-inflammatory effects of Hig on LPS-activated BV2 microglia and revealed the underlying mechanisms. Our data showed that Hig significantly inhibited the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), reactive oxygen species (ROS) as well as NO (mediated by iNOS) and PGE(2) (mediated by COX2) in LPS-activated BV2 cells. Then we found that Hig suppressed NF-kappa B signaling pathway by inhibiting nuclear translocation of NF-kappa B/p65 subunit as well as degradation and phosphorylation of I kappa B alpha in cytoplasm, and the effect of Hig was intimately related to NF-kappa B inhibitor BAY-11-7082. Furthermore, we found that the anti-inflammatory effect of Hig were accompanied by the promotion of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor-2 (Nrf2) expression, which was partly reversed by protoporphyrin (SnPP) and Nrf2 siRNA, respectively. Taken together, our results demonstrated that Hig expressed significant anti-inflammatory and -oxidative effects by inhibiting NF-kappa B and activating Nrf2/HO-1 signaling pathways.
作者机构:
[夏伯候; 廖扬振; 庹勤慧] Hunan University of Chinese Medicine, Changsha, 410208, China;Engineering Center of Medicinal and Edible Functional Food, Hunan University of Chinese Medicine, Changsha, 410208, China;Institute of TCM Diagnostics, Changsha, 410208, China;Hunan Province Pharmacy “Twelve Five” Key Disciplines, Changsha, 410208, China;[陈光宇] Hunan University of Chinese Medicine, Changsha, 410208, China, Engineering Center of Medicinal and Edible Functional Food, Hunan University of Chinese Medicine, Changsha, 410208, China, Institute of TCM Diagnostics, Changsha, 410208, China
通讯机构:
[Liao, D.] H;Hunan University of Chinese MedicineChina
摘要:
Systematic evolution of ligands by exponential enrichment (SELEX) is a well-established technology for the screening of aptamers binding to various targets with relatively high specificity and affinity. The screened aptamers have shown great achievements in bio-sensing and targeted therapeutics, which in turn stimulate continuous development of SELEX technology. To date, many SELEX technologies have been established, such as cell-SELEX, mag-SELEX, capillary electrophoresis SELEX and some novel modifications of SELEX. This review highlights current screening technologies and comprehensively pinpoints their principles, pros and cons. Some main aptamers screened by SELEX or involved in clinical trials are summarized. While, there are still challenges in obtaining of aptamer with high affinity and in an efficient way. The limitations and possible future directions on the screening of aptamers are also outlined.
摘要:
Identification of biomarkers is essential for diagnosis, targeted therapy and prognosis evaluation of diseases, especially cancers. Currently, the number of ideal clinical biomarkers is still limited partially because of lacking efficient methods in biomarker discovery. Nucleic acid aptamers are artificial single-stranded DNA or RNA sequences that can selectively bind to various targets with high specificity and affinity. Moreover, aptamers possess desirable advantages, including easy synthesis, convenient modification, relative chemical stability and low immunogenicity. Recently, different aptamer-based strategies have been developed to facilitate the discovery of biomarkers. Based on cell-SELEX technology, the selected aptamers can be used to identify cell-surface protein biomarkers of different cancer cells. SOMAscan can analyze thousands of proteins of different biological samples, which becomes a multiplexed protein biomarker discovery platform. Additionally, secreted protein biomarkers can be discovered by aptamers screened through secretome SELEX. In order to facilitate the identification of target proteins, several covalent cross-linking strategies have been developed, such as aptamer-based affinity labeling (ABAL), DNA-templated aptamer and protein-aptamer template (PAT). In this review, we mainly highlight the emerging nucleic acid aptamer-based biomarker discovery strategies and demonstrate their unique technological advantages in discovering cancer biomarkers. The challenges and perspectives of aptamer-based methods are also discussed. (C) 2019 Elsevier B.V. All rights reserved.
作者机构:
[谢梦洲; 陈光宇] Engineering Center of Medicinal and Edible Functional Food, Hunan University of Chinese Medicine, Changsha, 410208, China;College of Pharmacy of Hunan University of Chinese Medicine, Changsha, 410208, China;[杨崧; 刘平安] Druggability of Traditional Chinese Medicine and Preparations, Key Laboratory of Hunan Province, Changsha, 410208, China;Key Disciplinary of “The 12th Five-Year Plan” of Pharmacy in Hunan Province, Changsha, 410208, China;[何群] Engineering Center of Medicinal and Edible Functional Food, Hunan University of Chinese Medicine, Changsha, 410208, China, College of Pharmacy of Hunan University of Chinese Medicine, Changsha, 410208, China, Key Disciplinary of “The 12th Five-Year Plan” of Pharmacy in Hunan Province, Changsha, 410208, China
通讯机构:
[He, Q.] E;Engineering Center of Medicinal and Edible Functional Food, China