Nanoscintillator Coating: A Key Parameter That Strongly Impacts Internalization, Biocompatibility, and Therapeutic Efficacy in Pancreatic Cancer Models

Author:

Aubrun Fulbert Clémentine12,Chaput Frédéric3,Stelse‐Masson Sarah12,Henry Maxime2,Chovelon Benoit45,Bohic Sylvain16,Brueckner Dennis7,Garrevoet Jan7,Moriscot Christine8,Gallet Benoit9,Vollaire Julien2,Nicoud Olivier2,Lerouge Frédéric3,Denis‐Quanquin Sandrine10,Jaurand Xavier10,Jacquet Thibault12,Nomezine Anthony1,Josserand Véronique2,Coll Jean‐Luc2ORCID,Ravanat Jean‐Luc11,Elleaume Hélène1,Bulin Anne‐Laure2ORCID

Affiliation:

1. Université Grenoble Alpes, INSERM, UA 07 Synchrotron Radiation for Biomedicine Grenoble France

2. Université Grenoble Alpes INSERM U 1209, CNRS UMR 5309, Team Cancer Targets and Experimental Therapeutics, Institute for Advanced Biosciences 38000 Grenoble France

3. Université de Lyon Laboratoire de Chimie, École Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5182 46 Allée d’Italie F69364 Lyon France

4. Université Grenoble Alpes Département de Pharmacochimie Moléculaire, CNRS, UMR 5063 F‐38041 Grenoble France

5. Service de Biochimie SB2TE Institut de Biologie et Pathologie, CHU Grenoble Alpes 38041 Grenoble France

6. ESRF – The European Synchrotron Radiation Facility 38043 Grenoble France

7. Deutsches Elektronen‐Synchrotron DESY Notkestr. 85 22607 Hamburg Germany

8. Université Grenoble Alpes EMBL, Integrated Structural Biology Grenoble (ISBG), UAR 3518, CNRS, CEA 71 avenue des Martyrs F‐38042 Grenoble France

9. Université Grenoble Alpes Institut de Biologie Structurale (IBS), CEA, CNRS 38000 Grenoble France

10. Université Lyon 1 Centre Technologique des Microstructures F‐69622 Villeurbanne France

11. Université Grenoble Alpes, CEA, CNRS, Grenoble INP, SyMMES UMR 5819 F‐38000 Grenoble France

Abstract

Pancreatic cancer is associated with a poor prognosis despite multimodal treatments. To improve the efficacy of radiotherapy, the use of nanoscintillators is emerging. Made of high‐Z elements, they absorb X‐rays more efficiently than tissues and can locally enhance the radiation dose provided they have accumulated near tumor cells. This study focuses on the role of the coating, a key parameter that controls both in vitro and in vivo properties of nanoparticles, including their internalization, biocompatibility, and therapeutic efficacy. Polyethylene glycol and tripolyphosphate molecules are used to coat lanthanum fluoride nanoscintillators, and their properties are evaluated on pancreatic cancer models. The experiments demonstrate a higher internalization of the nanoparticles when coated with tripolyphosphate, in both 2D and 3D culture models, correlating with greater efficacy under X‐rays, which may be associated with higher radiation dose‐enhancement. The nanoparticles are also injected intravenously in healthy or tumor‐bearing mice in order to study their toxicity, pharmacokinetics, and biodistribution. Despite a strong liver and spleen accumulation, especially for the tripolyphosphate‐coated nanoparticles, no toxicity is observed for either coating. Because they show promising radiation dose‐enhancement in vitro in both culture models and a limited toxicity in vivo, polyethylene glycol‐coated nanoparticles are good candidates for biomedical applications.

Publisher

Wiley

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3