JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
·
2024
·Vol. 67
·期 11
·384-391
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IF 0.9
Shuhua He,Lina Jia,Xiaobei Zheng,Yang Wang,Yuxia Liu,Lan Zhang
Programmed death-ligand 1 (PD-L1) expression is related to the efficacy and prognosis in triple-negative breast cancer. This study employed an indirect labeling method to synthesize [ 125 I]PI-Atezolizumab. The in vitro stability of [ 125 I]PI-Atezolizumab was assessed through incubation in phosphate buffered saline and fetal bovine serum, revealing sustained stability. Specific binding of [ 125 I]PI-Atezolizumab to MDA-MB-231 cells expressing humanized PD-L1 was assessed through in vitro incubation, yielding a K d value comparable to that of Atezolizumab. This suggests that the labeling process did not compromise the affinity of the Atezolizumab to PD-L1. Subsequently, pharmacokinetic studies were conducted in normal mice and biodistribution experiments in tumor-bearing mice. A comparison of the biodistribution results between [ 125 I]PI-Atezolizumab and 125 I-labeled Atezolizumab indicated better in vivo stability for the former. Single photon emission computed tomography (SPECT)/CT imaging further confirmed the targeted specificity of [ 125 I]PI-Atezolizumab for PD-L1 in MDA-MB-231 xenografts, which were validated by immunohistochemistry staining. This research underscores the utility of [ 125 I]PI-Atezolizumab, prepared via indirect labeling, for monitoring PD-L1 in triple-negative breast cancer models.
研究领域:
肿瘤学
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分子影像学
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放射性药物
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癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Deliang Zhang,Rongqiang Zhuang,Jindian Li,Yuting Lv,Xia Yang,Weimin Pan,Xianzhong Zhang
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease with poor prognosis. Evidence has shown that vimentin is a key regulator of lung fibrogenesis. 99mTc-labeled N-acetylglucosamine-polyethyleneimine (NAG-PEI), a vimentin-targeting radiotracer, was used for the early diagnosis of IPF, and NAG-PEI was also used as a therapeutic small interfering RNA (siRNA) delivery vector for the treatment of IPF in this study. Single-photon emission-computed tomography (SPECT) imaging of bleomycin (BM)- and silica-induced IPF mice with 99mTc-labeled NAG-PEI was performed to visualize pulmonary fibrosis and monitor the treatment efficiency of siRNA-loaded NAG-PEI, lipopolysaccharide (LPS, a tolerogenic adjuvant), or zymosan (ZYM, an immunostimulant). The lung uptakes of 99mTc-NAG-PEI in the BM- and silica-induced IPF mice were clearly and directly correlated with IPF progression. The lung uptake of 99mTc-NAG-PEI in the NAG-PEI/TGF-β1-siRNA treatment group or LPS treatment group was evidently lower than that in the control group, while the lung uptake of 99mTc-NAG-PEI was significantly higher in the ZYM treatment group compared to that in the control group. These results demonstrate that NAG-PEI is a potent MicroSPECT imaging-guided theranostic platform for IPF diagnosis and therapy.
研究领域:
肺病学
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放射学
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分子生物学
·
诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2022
·
IF 9.965
Ningyue Yu,Linzhou Zhao,Danling Cheng,Mengbin Ding,Yan Lyu,Jinhua Zhao,Jingchao Li
Theranostics with integrations of both imaging and therapeutic elements can enable early diagnosis and effective treatment of cancer. Herein, we report the development of radioactive semiconducting polymer nanoparticles (rSPNs) for multimodal cancer theranostics. Such rSPNs constructed through labeling poly(ethylene glycol) (PEG) grafted SPNs with iodine-131 ( 131 I) exhibit ideal photothermal property, excellent singlet oxygen ( 1 O 2 ) generating ability and good radiolabeling stability. Owing to their small particle dimension and PEG surface corona, rSPNs show an effective accumulation into subcutaneous tumors of living mice after systemic administration. The good fluorescence property and stable radiolabeling of rSPNs enable contrast signals for near-infrared (NIR) fluorescence and single photon emission computed tomography (SPECT) dual-model imaging of tumors. Moreover, rSPNs provide combinational action of photothermal therapy (PTT), photodynamic therapy (PDT) and radiotherapy under NIR laser irradiation, resulting in much higher therapeutic efficacy in inhibiting tumor growth and metastasis relative to SPNs-mediated treatment. This study thus offers a multifunctional organic nanosystem for multimodal cancer theranostics.
研究领域:
癌症诊疗学
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放射学
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纳米医学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Xinyi Li,Yuyi Qian,Xin Lu,Mingzhen Xu,Simin He,Jianping Zhang,Shaoli Song
Transarterial radioembolization (TARE) is a recommended locoregional strategy for intermediate hepatocellular carcinoma (HCC), whereas, the effect is insufficient to reverse the immunosuppression tumor microenvironment, and the overall benefits for patients remain to be improved. In this study, a multifunctional microsphere (MS) 131 I-ICT/R848-MS is developed to propose an approach combined with TARE, icaritin (ICT) and immune modulator resiquimod (R848). ICT and iodine-131 ( 131 I) radiation can induce immunogenic cell death, which, in combination with R848, will boost dendritic cell (DC) maturation. Decellularized liver model and SPECT/CT imaging revealed high specificity and long retention of microspheres. Radioactive distribution of 131 I in tumor on 7 d following 131 I-MS injection was over 7 times of that in normal liver tissue (4.26 ± 1.21 % ID/g vs 0.57 ± 0.23 % ID/g). 131 I-ICT/R848-MS embolization brought significant immune activation, where the ratio of cytotoxic T lymphocytes to regulatory T cells in tumor sites upregulated from 1.75 ± 0.20 to 24.31 ± 1.79, and DC maturation in lymph nodes increased from 8.90 ± 1.51 % to 34.70 ± 3.12 %. Enhanced anti-tumor efficacy with no relapse was proved in rat orthotopic N1S1 HCC models. These results demonstrated the great potential of this multifunctional embolic agent to treat HCC through transarterial radio-immuno-chemoembolization (TARICE).
研究领域:
肿瘤学
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放射肿瘤学
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免疫疗法
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医学影像
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药理学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Lan Wu,Lin-Ping Wu,Jingya Wu,Jin Sun,Zhonggui He,Cristina Rodríguez-Rodríguez,Katayoun Saatchi,Lea Ann Dailey,Urs O. Häfeli,Dongmei Cun,Mingshi Yang
Pulmonary delivery of small interfering RNA (siRNA)-based drugs is promising in treating severe lung disorders characterized by the upregulated expression of disease-causing genes. Previous studies have shown that the sustained siRNA release in vitro can be achieved from polymeric matrix nanoparticles based on poly(lactide-co-glycolide) (PLGA) loaded with lipoplexes (LPXs) composed of cationic lipid and anionic siRNA (lipid–polymer hybrid nanoparticles, LPNs). Yet, the in vivo efficacy, potential for prolonging the pharmacological effect, disposition, and safety of LPNs after pulmonary administration have not been investigated. In this study, siRNA against enhanced green fluorescent protein (EGFP-siRNA) was either assembled with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) to form LPX or co-entrapped with DOTAP in PLGA nanoparticles to form LPNs. The disposition and clearance of LPXs and LPNs in mouse lungs were studied after intratracheal administration by using single-photon emission computed tomography/computed tomography (SPECT/CT) and gamma counting. Fluorescence spectroscopy, Western blot, and confocal laser scanning microscopy were used to evaluate the silencing of the EGFP expression mediated by the LPXs and LPNs after intratracheal administration to transgenic mice expressing the EGFP gene. The in vivo biocompatibility of LPXs and LPNs was investigated by measuring the cytokine level, total cell counts in bronchoalveolar lavage fluid, and observing the lung tissue histology section. The results showed that the silencing of the EGFP expression mediated by LPNs after pulmonary administration was both prolonged and enhanced as compared to LPXs. This may be attributed to the sustained release characteristics of PLGA, and the prolonged retention in the lung tissue of the colloidally more stable LPNs in comparison to LPXs, as indicated by SPECT/CT. The presence of PLGA effectively alleviated the acute inflammatory effect of cationic lipids to the lungs. This study suggests that PLGA-based LPNs may present an effective formulation strategy to mediate sustained gene silencing effects in the lung via pulmonary administration.
研究领域:
药剂学
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纳米技术
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分子生物学
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肺科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·
IF 6.6
Yunfei Lian,Fenyan Feng,Xinwang Meng,Yue Hu,Meirong Huo,Guangji Wang,Juan Li
Integration of multi-modal imaging techniques and various cancer treatments based on their respective characteristics would be beneficial for enhancing anticancer efficacy. Exploiting an “all-in-one” nanoparticle with high biocompatibility has attracted widespread attention. Herein, two clinically proven modalities, human serum albumin (HSA) and indocyanine green (ICG), were selected to create HSA-stable barium sulfonate nanoparticles (HSA@ICG–Ba) through the reaction of a sulfonic acid group with barium ions. Our nano-probe showed excellent optical properties and X-ray absorption capacity, which can be applied in tumor theranostics. Utilizing the rich tumor accumulation of HSA@ICG–Ba, this nanoparticle can obtain multifaceted tumor information through fluorescence (FL), computerized tomography (CT), photoacoustic (PA) imaging, and single photon emission computed tomography (SPECT) imaging. Additionally, radiation sensitization therapy and photothermal therapy based on HSA@ICG–Ba were evaluated using both in vitro and in vivo models. The efficacy of tumor radiotherapy can be further improved by mild hyperthermia owing to the relieved tumor hypoxia. Finally, the favorable safety profile of HSA@ICG–Ba is confirmed by blood index analysis and tissue section observation. Therefore, this study explored an “all-in-one” barium sulfonate nanoparticle with high biocompatibility for FL/CT/PA/SPECT imaging-guided synergetic photothermal-radiotherapy of tumors, providing a new approach and potential pathway for tumor theranostics.
研究领域:
生物医学工程
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纳米技术
·
癌症治疗
·
医学成像
✓ 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）