MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Huan Ma,Feize Li,Guohua Shen,Huawei Cai,Weihao Liu,Tu Lan,Yuanyou Yang,Jijun Yang,Jiali Liao,Ning Liu
As an excellent target for cancer theranostics, fibroblast activation protein (FAP) has become an attractive focus in cancer research. A class of FAP inhibitors (FAPIs) with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold were developed, which displayed nanomolar affinity and high selectivity. Compared with 90Y, 177Lu, 225Ac, and 188Re, 211At seems to be more favored as a therapeutic candidate for FAPI tracers which have fast washout and short retention in tumor sites. Thus, the current study reported the synthesis of two FAPI precursors for 211At and 131I labeling and the preliminary evaluation of 131I-labeled FAPI analogues for cancer theranostics. FAPI variants with stannyl precursors were successfully synthesized and labeled with 131I using a radioiododestannylation reaction. Two radioactive tracers were obtained with high radiochemical purity over 99% and good radiochemical yields of 58.2 ± 1.78 and 59.5 ± 4.44% for 131I-FAPI-02 and 131I-FAPI-04, respectively. Both tracers showed high specific binding to U87MG cells in comparison with little binding to MCF-7 cells. Compared to 131I-FAPI-02, 131I-FAPI-04 exhibited higher affinity, more intracellular uptake, and longer retention time in vitro. Biodistribution studies revealed that both tracers were mainly excreted through the kidneys as well as the hepatobiliary pathway due to their high lipophilicity. In addition, higher accumulation, longer dwell time, and increased tumor-to-organ ratios were achieved by 131I-FAPI-04, which was clearly demonstrated by SPECT/CT imaging. Furthermore, intratumor injection of 131I-FAPI-04 significantly suppressed the tumor growth in U87MG xenograft mice without significant toxicity observed. The above results implied that FAP-targeted alpha endoradiotherapy (specific to 211At) should be used to treat tumors in the near future, considering the chemical similarity between iodine and astatine can ensure the labeling of the latter onto the designed FAPIs.
研究领域:
肿瘤学
·
核医学
·
分子影像学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
·
2018
·Vol. 316
·期 2
·685-690
·
IF 1.181
Song Hu,Wang Yunhan,Wang Jing,Wang Guanquan,He Jiaheng,Wei Hongyuan,Luo Shunzhong
For the superiority of graphene quantum dots (GQDs) in bioimaging and drug delivery carrier, GQDs bring new opportunities for theranostics of diseases. In this study, GQDs were successfully prepared and labeled with 131 I. The in vitro properties, biodistribution and SPECT imaging of 131 I-GQDs were investigated. The uptake of 131 I-GQDs at tumor sites can be clearly observed via SPECT imaging and T/B and T/M ratios increase with increasing time, which can contribute to enhanced permeability and retention (EPR) effect.
研究领域:
核医学
·
放射学
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Jiangnan Xu,Xiu Luo,Weiwei Su,Guorong Jia,Huawei Cai,Danni Li,Rou Li,Xiangdong Wang,Yefa Yang,Tao Wang,Changjing Zuo
Transarterial radioembolization (TARE) is a primary palliative treatment for advanced liver cancer. Nonetheless, its therapeutic efficacy is frequently hindered by resistance to tumor cell apoptosis induced by inter-radiotherapy. Induction of multiple cell death modalities provides a potential solution to this challenge. Ferroptosis, a distinct form of cell death from apoptosis, is dependent on the intracellular Fe2+-mediated Fenton reaction for the production of hydroxyl radicals (·OH) and is gaining recognition as a promising approach for cancer treatment. In this study, we synthesized a therapeutic radionuclide iodine-131 (131I)-based TARE agent by combining 131I-labeled iron-based MIL-88B(Fe) nanoparticles (NPs) (abbreviated as 131I-MIL-88B(Fe)) with Lipiodol to achieve a combined apoptosis–ferroptosis tumor therapy. Specifically, a mixture of Lipiodol and 131I-MIL-88B(Fe) NPs was injected into the liver tumors through the hepatic artery. Lipiodol blocks the arterial blood supply of the tumor, causing tumor tissue necrosis, whereas 131I inter-radiotherapy damages deoxyribonucleic acid (DNA) through direct action or indirectly via the production of ·OH through H2O radiolysis, leading to tumor cell apoptosis. Importantly, hydrated electrons (eaq–), a byproduct of H2O radiolysis, promoted the conversion of Fe3+ to Fe2+ in MIL-88B(Fe) NPs, enhancing the efficacy of the Fenton reaction and triggering ferroptosis. In vitro experiments demonstrated that compared to 131I alone, 131I-MIL-88B(Fe) NPs significantly enhanced ferroptosis-mediated tumor cell death due to 131I-induced Fe2+ production, which increased catalytic activity in the Fenton reaction. In a rat model bearing orthotopic N1S1 liver tumors, TARE with Lipiodol and 131I-MIL-88B(Fe) NPs induced tumor cell necrosis, apoptosis, and ferroptosis, resulting in improved therapeutic outcomes. This study leverages eaq– to facilitate Fe3+/Fe2+ conversion for efficient ferroptosis, turning waste into a valuable resource. This demonstrated the innovative integration of multiple treatment strategies to augment the efficacy of TARE in liver cancer therapy.
研究领域:
医学
·
肿瘤学
·
放射治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2019
·Vol. 15
·期 46
·1903628
·
IF 10.856
Jiawen Chen,Chao Liang,Xuejiao Song,Xuan Yi,Kai Yang,Liangzhu Feng,Zhuang Liu
It is hard for current radionuclide therapy to render solid tumors desirable therapeutic efficacy owing to insufficient tumor-targeted delivery of radionuclides and severe tumor hypoxia. In this study, a biocompatible hybrid protein nanoreactor composed of human serum albumin (HSA) and catalase (CAT) molecules is constructed via glutaraldehyde-mediated crosslinking. The obtained HSA-CAT nanoreactors (NRs) show retained and well-protected enzyme stability in catalyzing the decomposition of H 2 O 2 and enable efficient labeling of therapeutic radionuclide iodine-131 ( 131 I). Then, it is uncovered that such HSA-CAT NRs after being intravenously injected into tumor-bearing mice exhibit efficient passive tumor accumulation as vividly visualized under the fluorescence imaging system and gamma camera. As the result, such HSA-CAT NRs upon tumor accumulation would significantly attenuate tumor hypoxia by decomposing endogenous H 2 O 2 produced by cancer cells to molecular oxygen, and thereby remarkably improve the therapeutic efficacy of radionuclide 131 I. This study highlights the concise preparation of biocompatible protein nanoreactors with efficient tumor homing and hypoxia attenuation capacities, thus enabling greatly improved tumor radionuclide therapy with promising potential for future clinical translation.
研究领域:
生物医学工程
·
肿瘤学
·
放射医学
✓ 已验证
DOI
PubMed
高影响因子
ANTI-CANCER DRUGS
·
2021
·Vol. 33
·期 1
·19
·
IF 2.248
Liu Shengli,Liu Honglian,Sun Hao,Deng Shengming,Yue Ling,Weng Zhen,Yang Jianfeng,Zuo Bin,He Yang,Zhang Bin
Albendazole (ABZ), a clinical antiparasitic drug, has shown potential antitumor effects in various tumors. Herein, we prepared dimeric cRGD [(cRGD) 2 ] modified human serum albumin (HSA) nanosystem to co-delivery of albendazole (ABZ) and iodine-131 ( 131 I) for chemoradiotherapy of triple-negative breast cancer (TNBC). [email protected] NPs were synthesized by the self-assembly method. 131 I-(cRGD) 2 / [email protected] NPs were fabricated through covalently binding [email protected] NPs with (cRGD) 2 peptides, followed by chloramine T direct labeling with 131 I. In vitro therapeutic effects on TNBC (MDA-MB-231 and 4T1 cells) were determined using MTT assay, crystal violet assay, wound-healing assay and western blotting analysis. In vivo treatment was performed using 4T1-bearing mice, and the tumor-targeting efficacy was assessed by gamma imaging. The distribution of NPs was quantitatively analyzed by detecting the gamma counts in tumor and main organs. The nanoparticles possessed negative charge, moderate size and good polydispersity index. Dual responding to pH and redox, the in vitro release rate of ABZ was more than 80% in 72 h. In vitro, NPs inhibited the proliferation of TNBC cells in a concentration-dependent manner and decreased cell migration. Western blotting analysis showed that the NPs, as well as free ABZ, cell-dependently induced autophagy and apoptosis by restraining or promoting the expression of p-p38 and p-JNK MAPK. In vivo, gamma imaging exhibited an earlier and denser radioactivity accumulation in tumor of 131 I-(cRGD) 2 / [email protected] NPs compared to NPs free of (cRGD) 2 conjugating. Furthermore, 131 I-(cRGD) 2 / [email protected] NPs significantly suppressed tumor growth by restraining proliferation and promoting apoptosis in vivo. Our study suggested that the nanoparticles we developed enhanced tumor-targeting of ABZ and increased antitumor effects by combination of chemotherapy and radiotherapy.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
IUBMB LIFE
·
2022
·Vol. 74
·期 5
·433-445
·
IF 4.709
Chunmei Zhang,Jinyan Chai,Qiang Jia,Jian Tan,Zhaowei Meng,Ning Li,Menghui Yuan
Bovine serum albumin (BSA) has been employed as a mild biological template in nanoscale particles. Copper sulfide (CuS) has been used for photothermal therapy (PTT) in several studies. In this study, we aimed to synthesize the 131 I-labeled BSA-modified CuS nanoparticles ( 131 I-BSA@CuS), with attributes of both radiotherapy and PTT, as a therapeutic agent against anaplastic thyroid carcinoma (ATC). BSA@CuS nanoparticles were prepared using the solvothermal reaction and then labeled with Na 131 I by the chloramine-T method. The products were characterized and their cytotoxicity was investigated in vitro and in vivo. The therapeutic efficacy of 131 I-BSA@CuS was evaluated in ARO cell (an ATC cell line) subcutaneous tumors. The nanoparticles showed good biocompatibility and low toxicity in vitro and in vivo. BSA@CuS rapidly and effectively converted the light energy from an 808 nm laser into thermal energy with a conversion efficiency of 28.07%. SPECT/CT imaging demonstrated that the accumulation of radioactivity peaked within 24 hr and resided in the tumors for 5 days post intratumoral injection. In vivo assays indicated that, compared to monotherapy, the synthesized nanoparticles employing both PTT and radiotherapy possess better therapeutic efficacy against tumors. The synthesized nanomaterial showed uniform dispersion, good stability and aqueous solubility, excellent photothermal properties, and long-term retention in ATC. Hence, combined radiotherapy and PTT can significantly inhibit tumor growth compared to monotherapy, and can be applied in clinical settings.
研究领域:
肿瘤学
·
放射医学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2018
·
IF 8.537
Qiufang Liu,Yuyi Qian,Panli Li,Sihang Zhang,Jianjun Liu,Xiaoguang Sun,Michael Fulham,Dagan Feng,Gang Huang,Wei Lu,Shaoli Song
Purpose: Transcatheter hepatic artery embolization therapy is a minimally invasive alternative for treating inoperable liver cancer but recurrence is frequent. Multifunctional agents, however, offer an opportunity for tumor eradication. In this study, we were aim to synthesized poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating hollow CuS nanoparticles (HCuSNPs) and paclitaxel (PTX) that were then labeled with radioiodine-131 ( 131 I) to produce 131 I-HCuSNPs-MS-PTX. This compound combines the multi-theranostic properties of chemotherapy, radiotherapy and photothermal therapy. In addition, it can also be imaged with single photon emission computed tomography (SPECT) imaging and photoacoustic imaging. Methods: We investigated the value of therapeutic and imaging of 131 I-HCuSNPs-MS-PTX in rats bearing Walker-256 tumor transplanted in the liver. After the intra-arterial (IA) injection of 131 I-HCuSNPs-MS-PTX, 18 F-Fluorodeoxyglucose ( 18 F-FDG) micro-positron emission tomography/computed tomography (micro-PET/CT) imaging was used to monitor the therapeutic effect. PET/CT findings were verified by immunohistochemical analysis. SPECT/CT and photoacoustic imaging were performed to demonstrate the distribution of 131 I-HCuSNPs-MS-PTX in vivo . Results : We found that embolization therapy in combination with chemotherapy, radiotherapy and photothermal therapy offered by 131 I-HCuSNPs-MS-PTX completely ablated the transplanted hepatic tumors at a relatively low dose. In comparison, embolization monotherapy or combination with one or two other therapies had less effective anti-tumor efficacy. The combination of SPECT/CT and photoacoustic imaging effectively confirmed microsphere delivery to the targeted tumors in vivo and guided the near-infrared laser irradiation. Conclusion : Our study suggests that there is a clinical theranostic potential for imaging-guided arterial embolization with 131 I-HCuSNPs-MS-PTX for the treatment of liver tumors.
研究领域:
肿瘤学
·
放射学
·
药理学
·
医学影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2025
·
IF 5.7
Hehua Xiong,Yiling Ruan,Huihui Liu,Xuan Liu,Xiaolian Sun
Cerenkov radiation induced photodynamic therapy (CR-PDT) offers a promising approach to overcome the dependency on external light sources and associated tissue penetration limitations. However, the therapeutic efficacy of CR-PDT is constrained by tumor hypoxia and the intrinsically short half-life and limited diffusion distance of reactive oxygen species (ROS). Herein, we propose a tumor acidity-triggered, mitochondria-targeted CR-PDT strategy to amplify the ROS generation for enhanced therapeutic efficacy. The mitochondria-targeted photosensitizers (TTCPP) are encapsulated within amphiphilic polymers, functionalized with acidity-responsive moiety and 131I labeling group, forming 131I-TTCPP nanoparticles (131I-TTCPP NPs). Under physiological conditions, 131I-TTCPP NPs exhibit minimal phototoxicity due to aggregation-caused quenching (ACQ). Upon encountering the acidic tumor microenvironment, 131I-TTCPP NPs disintegrate, restoring the photodynamic activity of TTCPP. Compared to non-targeted photosensitizers TCPP, the released mitochondria-targeted TTCPP effectively localizes to mitochondria and undergoes self-activation by 131I, generating significantly higher levels of ROS, which results in more severe mitochondrial dysfunction and enhanced apoptosis. Our findings demonstrate that coupling mitochondria targeting with self-activated CR-PDT provides a more effective and safer option for cancer treatment.
研究领域:
肿瘤学
·
纳米医学
·
光动力治疗
·
放射治疗
·
活性氧信号传导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
·
2019
·Vol. 319
·期 3
·1119-1125
·
IF 1.186
Wang Yunhan,Song Hu,Wang Guanquan,Yang Xia,Wang Jing,Wei Hongyuan
In this study, we successfully synthesized polyethylene glycol (PEG) and folic acid (FA) co-functionalized graphene quantum dots (GQDs) to improve the biocompatibility and tumor-targeting ability of GQDs simultaneously, and labeled GQDs–PEG–FA with 131 I for biological behavior evaluation. The in vitro properties, biodistribution and SPECT imaging of 131 I-GQDs–PEG–FA were investigated. The uptake of 131 I-GQDs–PEG–FA at tumor sites can be clearly examined via SPECT imaging, which can ascribe to enhanced permeability and retention effect and active targeting effect of FA to folate receptors. The results indicate that 131 I-GQDs–PEG–FA can be used as a radioactive probe for detection of tumor cells overexpressing folate receptor.
研究领域:
放射学
·
核医学
·
分子影像
·
生物材料
·
癌症研究
✓ 已验证
产品关联
DOI
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
·
放射学
·
纳米医学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Haidong Shen,Surui Chen,Chonghai Zhang,Teng Liu,Yugui Tao,Lin Hu,Kai Yang
Radioisotope therapy (RIT) is one of clinical treatment for tumors, which can not only directly kill tumor cells, but also enhance anti-tumor immune response by inducing tumor cell immunogenic cell death (ICD). However, significant challenges for RIT are the low radiolabeling efficiency, as well as tumor targeting issues. Bacterial outer membrane vesicles (OMVs), which are natural nano-vesicles secreted by Gram-negative bacteria, are now garnering significant attention in cancer therapy due to their tumor-targeting and immunotherapeutic potential. Herein, we construct an engineering delivery platform based on OMVs to achieve efficient labeling of radioactive iodine and improve radio-immunotherapy ( 131 I-STATH-OMV-PEG). Firstly, high tyrosine-rich protein statherin (STATH) is integrated onto the surface of OMVs (STATH-OMV) through bioengineered technology. The obtained STATH-OMV is coated with polyethylene glycol (PEG) and then labeled with radionuclide iodine-131 ( 131 I-STATH-OMV-PEG), which exhibit excellent radiolabeling efficiency due to the integration of STATH. More importantly, 131 I-STATH-OMV-PEG could also boost DC maturation and produce anti-tumor cytokines, thereby enhancing the systemic anti-tumor immune response induced by RIT. Additionally, 131 I-STATH-OMV-PEG could inhibit orthotopic colon cancer, induce systemic immune memory effect and prevent tumor invasion. In summary, this study proposes an OMV-centered RIT delivery system that ensures proficient labeling of 131 I, thereby amplifying the therapeutic effect of RIT and opening up a promising approach for tumor radio-immunotherapy.
研究领域:
肿瘤学
·
放射生物学
·
免疫疗法
·
纳米技术
·
癌症治疗
✓ 已验证
DOI
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
·
放射肿瘤学
·
免疫疗法
·
医学影像
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）