Pharmaceutics
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2024
·Vol. 16
·期 6
·744
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IF 4.9
Qianqian Long,Xinmin Zhao,Lili Gao,Mengyuan Liu,Feng Pan,Xihui Gao,Changyou Zhan,Yang Chen,Jialei Wang,Jun Qian
Background:Nanoparticles conjugated with fluorescent probes have versatile applications, serving not only for targeted fluorescent imaging but also for evaluating the in vivo profiles of designed nanoparticles. However, the relationship between fluorophore density and nanoparticle behavior remains unexplored.Methods:The IR783-modified liposomes (IR783-sLip) were prepared through a modified ethanol injection and extrusion method. The cellular uptake efficiency of IR783-sLip was characterized by flow cytometry and fluorescence microscope imaging. The effects of IR783 density on liposomal in vivo behavior were investigated by pharmacokinetic studies, biodistribution studies, and in vivo imaging. The constitution of protein corona was analyzed by the Western blot assay.Results:Dense IR783 modification improved cellular uptake of liposomes in vitro but hindered their blood retention and tumor imaging performance in vivo. We found a correlation between IR783 density and protein corona absorption, particularly IgM, which significantly impacted the liposome performance. Meanwhile, we observed that increasing IR783 density did not consistently improve the effectiveness of tumor imaging.Conclusions:Increasing the density of modified IR783 on liposomes is not always beneficial for tumor near-infrared (NIR) imaging yield. It is not advisable to prematurely evaluate novel nanomaterials through fluorescence dye conjugation without carefully optimizing the density of the modifications.
研究领域:
药剂学
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生物医学工程
·
分子影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2016
·
IF 7.145
Huan Tang,Sheng-Tao Yang,Yi-Fan Yang,Da-Ming Ke,Jia-Hui Liu,Xing Chen,Haifang Wang,Yuanfang Liu
As a novel fluorescent probe in the second near-infrared window, Ag2Se quantum dots (QDs) exhibit great prospect in in vivo imaging due to their maximal penetration depth and negligible background. However, the in vivo behavior and toxicity of Ag2Se QDs still largely remain unknown, which severely hinders their wide-ranging biomedical applications. Herein, we systematically studied the blood clearance, distribution, transformation, excretion, and toxicity of polyethylene glycol (PEG) coated Ag2Se QDs in mice after intravenous administration with a high dose of 8 μmol/kg body weight. QDs are quickly cleared from the blood with a circulation half-life of 0.4 h. QDs mainly accumulate in liver and spleen and are remarkably transformed into Ag and Se within 1 week. Ag is excreted from the body readily through both feces and urine, whereas Se is excreted hardly. The toxicological evaluations demonstrate that there is no overt acute toxicity of Ag2Se QDs to mice. Moreover, in regard to the in vivo stability problem of Ag2Se QDs, the biotransformation and its related metabolism are intensively discussed, and some promising coating means for Ag2Se QDs to avert transformation are proposed as well. Our work lays a solid foundation for safe applications of Ag2Se QDs in bioimaging in the future.
研究领域:
生物医学
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药理学
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毒理学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2023
·
IF 5
Lixue Ma,Zhaohua Li,Jiancheng Fei,Mo Li,Bingyang Liu,Baocheng Tian,Yanhua Liu,Qiang Fu
Nanocrystals (NCs) are considered as an effective strategy for the formulation of intravenous injections for poorly water-soluble drugs, despite they are metastable dispersions. Typically, stabilizers are essential for the maintenance of physical stability, and they are important compositions for NCs. However, whether the stabilizers have impacts on the in vivo behaviors of NCs after intravenous injection are unknown. In this study, three meloxicam NCs (MLXNCs) were each formulated with a different steric stabilizer (PEG 400, lecithin and PVP-K17). The developed MLXNC PEG , MLXNC Lec and MLXNC PVP all had particle size of about 250 nm and shared the same crystal form. All three formulations had similar pharmacokinetic profiles and therapeutic efficacy, with no statistically significant differences. Overall results provided evidence that stabilizers have negligible effects on the in vivo behaviors of intravenous NCs and stress the importance of physical stability for formulation development.
研究领域:
药剂学
·
药物代谢动力学
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产品关联
DOI
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2019
·
IF 2.705
Meilin Shi,Lina Dong,Shaohui Zheng,Pingfu Hou,Lulu Cai,Mingming Zhao,Xiuli Zhang,Qi Wang,Jingjing Li,Kai Xu
“Bottom-up” method is a popular approach for the preparation of molybdenum disulfide quantum dots (MoS 2 QDs) benefitting from less time consumption and no high-powered sonication required. But the relatively low fluorescent quantum yield of the obtained MoS 2 QDs and the rare study about their in vivo behavior stimulate us to do more research in this area. In this paper, we proposed a “bottom-up” hydrothermal method to prepare MoS 2 QDs with a quantum yield (QY) of 34.55% by optimizing a series of reaction conditions. The successful fluorescence imaging of tumor cells in vitro and in vivo as well as the systematic in vivo behavior study such as biocompatibility, biodistribution and metabolism route provided the good basis for their wider biomedical applications.
研究领域:
生物医学工程
·
材料科学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
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2018
·
IF 13.709
Xuanrong Sun,Guowei Wang,Hao Zhang,Shiqi Hu,Xin Liu,Jianbin Tang,Youqing Shen
Polymer micelles are one of the most investigated nanocarriers for drug delivery; many have entered clinical trials and some are in clinic use, but their delivery systems have not yet shown the expected high therapeutic efficacy in clinics. Further understanding their in vivo behaviors, particularly how quickly and by what mechanism polymer micelles are cleared (i.e., via micelles or unimers) once injected, is key to solving this dilemma. Herein, we hope to answer these questions for the clinically relevant polyethylene glycol-block-poly(ε-caprolactone) (PEG-PCL) and PEG-block-poly(d,l-lactide) (PEG-PDLLA) micelles. A small fraction of the hydrophobic chain ends was conjugated with a pair of fluorescence resonance energy transfer (FRET) dyes, Cy5 and Cy5.5, and used to fabricate FRET micelles whose FRET efficiency was correlated to the percentage of polymer chains in the micelles, the micelle degree. In vitro, serum proteins induced PEG-PCL micelle dissociation to some extent; mouse serum or blood surprisingly did not induce micelle dissociation but once with shear applied by a microfluidic channel caused most PEG-PCL micelles dissociated. After intravenous administration in mice, the PEG-PCL or PEG-PDLLA micelles were quickly sequestered into the liver as unimers, and the micelle degree in the blood quickly decreased to about 20%. The FRET-imaging experiments showed that in blood vessels the micelles quickly dissociated into unimers, which were found associated with albumin in blood and in liver. Thus, it is concluded that, upon intravenous injection, the shear and the bloodborne proteins (particularly albumin) induced the most (∼80%) PEG-PCL and PEG-PDLLA micelles to quickly dissociate into unimers, which were sequestered by Kupffer cells, while intact micelles were difficult to clear. These micelles were able to penetrate tumors and were very stable with cell membranes, but dissociated gradually inside cells. These findings on in vivo micelle fate and the clearance mechanism are directional for the rational design of polymer micelles for improved therapeutics; particularly, improving micelle stability in blood is the prerequisite for surface functionalizations such as introducing targeting ligands.
研究领域:
药剂学
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生物医学工程
·
癌症治疗
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2020
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IF 10.317
Jinsong Tao,Zhengjie Wei,Yuan He,Xingyang Yan,Simon Ming-Yuen Lee,Xueqing Wang,Wei Ge,Ying Zheng
Understanding the behaviors of nanomedicines in vivo is one of the most important prerequisites for the design and optimization of nanomedicines. However, the in vivo tracking of nanomedicines in rodents is severely limited by the restricted imaging possibilities within these animals. To meet these needs, the FRET (fluorescence or Förster resonance energy transfer) imaging combined with visual zebrafish larvae model (7 dpf) was used to study the behaviors of polymeric micelles in vivo at high spatiotemporal resolution . Firstly, the FRET ordinary Pluronic micelles (OPMs) and disulfide bond crosslinked Pluronic micelles (CPMs) were synthesized to quantify their integrity in vitro and in vivo by FRET ratio. The behaviors and integrity of OPMs and CPMs in vivo were visually investigated in zebrafish larvae across the entire living organism and at cellular molecular level after intravenous microinjection . Results showed that OPMs were rapidly disassociated in circulation, then largely sequestrated by the endothelial cells (ECs) of caudal vein (CV) and liver in zebrafish larvae, which resulted in quick elimination from blood circulation. While the CPMs were more stable and escaped the sequestration by ECs of CV and liver, which prolonged their circulation in blood. Moreover, we pioneered to use the zebrafish model to reveal that polymeric micelles were eliminated through hepatobiliary pathway after disassociation. While the intact micelles were relatively difficult to eliminate. We further verified that the scavenger receptors of ECs but not the macrophages mainly mediated the elimination of polymeric micelles in CV and liver of zebrafish larvae. These finding on behaviors and elimination mechanisms of polymeric micelles in zebrafish model could contribute to the rational design and optimization of nanomedicines, further guide their studies in rodents.
研究领域:
药剂学
·
生物医学工程
·
分子影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2016
·
IF 3.902
Weifeng Lin,Guanglong Ma,Jiang Wu,Shengfu Chen
Poly(sulfobetaine methacrylate) (pSBMA) and poly(carboxybetaine methacrylate) (pCBMA) are two well-known zwitterionic polymers known for their excellent antifouling properties. In this work, these two zwitterionic polymers were compared both in vitro and in vivo . Both of them exhibited excellent antifouling properties and low macrophage uptake although there were negligible differences in resistance to nonspecific protein adsorption of their hydrogels and cell internalization of their star polymers. However, it is found that the β- Cyclodextrin-CBMA (CD-CBMA) showed a circulation time one order of magnitude longer than CD-SBMA, which implied that small differences in vitro may lead to a dramatic difference in vivo . This work demonstrated that pCBMA showed greater potential than pSBMA in biomedical applications.
研究领域:
生物材料学
·
医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）