Dataset Information

Radionuclide Imaging-Guided Chemo-Radioisotope Synergistic Therapy Using a ¹³¹I-Labeled Polydopamine Multifunctional Nanocarrier.

ABSTRACT: Development of biocompatible nanomaterials with multiple functionalities for combination of radiotherapy and chemotherapy has attracted tremendous attention in cancer treatment. Herein, poly(ethylene glycol) (PEG) modified polydopamine (PDA) nanoparticles were successfully developed as a favorable biocompatible nanoplatform for co-loading antitumor drugs and radionuclides to achieve imaging-guided combined radio-chemotherapy. It is demonstrated that PEGylated PDA nanoparticles can effectively load two different drugs including sanguinarine (SAN) and metformin (MET), as well as radionuclides ¹³¹I in one system. The loaded SAN and MET could inhibit tumor growth via inducing cell apoptosis and relieving tumor hypoxia, while labeling PDA-PEG with ¹³¹I enables in vivo radionuclide imaging and radioisotope therapy. As revealed by the therapeutic efficacy both in cell and animal levels, the multifunctional PDA nanoparticles (¹³¹I-PDA-PEG-SAN-MET) can effectively repress the growth of cancer cells in a synergistic manner without significant toxic side effects, exhibiting superior treatment outcome than the respective monotherapy. Therefore, this study provides a promising polymer-based platform to realize imaging-guided radioisotope/chemotherapy combination cancer treatment in future clinical application.

SUBMITTER: Li Z

PROVIDER: S-EPMC5993982 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Radionuclide Imaging-Guided Chemo-Radioisotope Synergistic Therapy Using a <sup>131</sup>I-Labeled Polydopamine Multifunctional Nanocarrier.

Li Zhiqiang Z Wang Baikui B Zhang Zheng Z Wang Bo B Xu Qiangqiang Q Mao Wenjie W Tian Jie J Yang Kai K Wang Fu F

Molecular therapy : the journal of the American Society of Gene Therapy 20180224 5

Development of biocompatible nanomaterials with multiple functionalities for combination of radiotherapy and chemotherapy has attracted tremendous attention in cancer treatment. Herein, poly(ethylene glycol) (PEG) modified polydopamine (PDA) nanoparticles were successfully developed as a favorable biocompatible nanoplatform for co-loading antitumor drugs and radionuclides to achieve imaging-guided combined radio-chemotherapy. It is demonstrated that PEGylated PDA nanoparticles can effectively lo ...[more]

PMID: 29567310

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Project description:Chemo-mild photothermal synergistic therapy can effectively inhibit tumor growth under mild hyperthermia, minimizing damage to nearby healthy tissues and skin while ensuring therapeutic efficacy. In this paper, we develop a multifunctional study based on polyhedral oligomeric sesquisiloxane (POSS) that exhibits a synergistic therapeutic effect through mild photothermal and chemotherapy treatments (POSS-SQ-DOX). The nanoplatform utilizes SQ-N as a photothermal agent (PTA) for mild photothermal, while doxorubicin (DOX) serves as the chemotherapeutic drug for chemotherapy. By incorporating POSS into the nanoplatform, we successfully prevent the aggregation of SQ-N in aqueous solutions, thus maintaining its excellent photothermal properties both in vitro and in vivo. Furthermore, the introduction of polyethylene glycol (PEG) significantly enhances cell permeability, which contributes to the remarkable therapeutic effect of POSS-SQ-DOX NPs. Our studies on the photothermal properties of POSS-SQ-DOX NPs demonstrate their high photothermal conversion efficiency (62.3%) and stability, confirming their suitability for use in mild photothermal therapy. A combination index value (CI = 0.72) verified the presence of a synergistic effect between these two treatments, indicating that POSS-SQ-DOX NPs exhibited significantly higher cell mortality (74.7%) and tumor inhibition rate (72.7%) compared to single chemotherapy and mild photothermal therapy. This observation highlights the synergistic therapeutic potential of POSS-SQ-DOX NPs. Furthermore, in vitro and in vivo toxicity tests suggest that the absence of cytotoxicity and excellent biocompatibility of POSS-SQ-DOX NPs provide a guarantee for clinical applications. Therefore, utilizing near-infrared light-triggering POSS-SQ-DOX NPs can serve as chemo-mild photothermal PTA, while functionalized POSS-SQ-DOX NPs hold great promise as a novel nanoplatform that may drive significant advancements in the field of chemo-mild photothermal therapy.

Project description:BackgroundProgrammed cell death 1 ligand 1(PD-L1) is overexpressed in many tumors. The radionuclide-labeled anti-PD-L1 monoclonal antibody can be used for imaging and therapy of PD-L1 overexpressing cancer. Here, we described 131I-labeled Atezolizumab (131I-Atezolizumab, targeting PD-L1) as a therapeutic agent for colorectal cancer with PD-L1 overexpression.Methods131I-Atezolizumab was prepared by the Iodogen method. The expression levels of PD-L1 in different human colorectal cells were determined by flow cytometry, western blot and cell binding assay. The immunoreactivity of 131I-Atezolizumab to PD-L1 high-expressing cells was determined by immunoreactive fraction. The killing abilities of different concentrations of 131I-Atezolizumab on cells with high and low expression of PD-L1 were detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Cerenkov luminescence imaging (CLI) and radioimmunotherapy (RIT) of 131I-Atezolizumab were performed on two human colorectal cancer models. The distribution and tumor targeting of 131I-Atezolizumab were evaluated by imaging. Tumor volume and survival time were used as indicators to evaluate the anti-tumor effect of 131I-Atezolizumab.ResultsThe expression level of PD-L1 in vitro determined by the cell binding assay was related to the data of flow cytometry and western blot. 131I-Atezolizumab can specifically bind to PD-L1 high-expressing cells in vitro to reflect the expression level of PD-L1. Immunoreactive fraction of PD-L1 high-expressing RKO cells with 131I-Atezolizumab was 52.2%. The killing ability of 131I-Atezolizumab on PD-L1 high-expressing cells was higher than that of low-expressing cells. CLI proved that the specific uptake level of tumors depends on the expression level of PD-L1. Effect of 131I-Atezolizumab RIT showed an activity-dependent tumor suppressor effect on RKO tumor-bearing mice with high PD-L1 expression. 131I-Atezolizumab (37 MBq) can improve the median survival time of mice (34 days), compared to untreated mice (27 days) (P = 0.027). Although a single activity(37 MBq) of 131I-Atezolizumab also inhibited the tumors of HCT8 tumor-bearing mice with low PD-L1 expression (P < 0.05), it could not prolong the survival of mice(P = 0.29).Conclusion131I-Atezolizumab can be used as a CLI agent for screening PD-L1 expression levels. It may be used as a radioimmunotherapy drug target for PD- L1 overexpressing tumors.

Dataset Information

Radionuclide Imaging-Guided Chemo-Radioisotope Synergistic Therapy Using a ¹³¹I-Labeled Polydopamine Multifunctional Nanocarrier.

Publications

Radionuclide Imaging-Guided Chemo-Radioisotope Synergistic Therapy Using a <sup>131</sup>I-Labeled Polydopamine Multifunctional Nanocarrier.

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Dataset Information

Radionuclide Imaging-Guided Chemo-Radioisotope Synergistic Therapy Using a 131I-Labeled Polydopamine Multifunctional Nanocarrier.

Publications

Radionuclide Imaging-Guided Chemo-Radioisotope Synergistic Therapy Using a <sup>131</sup>I-Labeled Polydopamine Multifunctional Nanocarrier.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Radionuclide Imaging-Guided Chemo-Radioisotope Synergistic Therapy Using a ¹³¹I-Labeled Polydopamine Multifunctional Nanocarrier.