一种 PEG 化的丙氯苯嗪脂质体制剂,可限制脑部暴露,但仍能保持动态胺 II 的活性:接受化疗 mAbs 的癌症患者的潜在辅助疗法

IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2024-01-08 DOI:10.1016/j.nano.2024.102733
Christopher N. Subasic , Fiona Simpson , Rodney F. Minchin , Lisa M. Kaminskas
{"title":"一种 PEG 化的丙氯苯嗪脂质体制剂,可限制脑部暴露,但仍能保持动态胺 II 的活性:接受化疗 mAbs 的癌症患者的潜在辅助疗法","authors":"Christopher N. Subasic ,&nbsp;Fiona Simpson ,&nbsp;Rodney F. Minchin ,&nbsp;Lisa M. Kaminskas","doi":"10.1016/j.nano.2024.102733","DOIUrl":null,"url":null,"abstract":"<div><p>Anti-cancer monoclonal antibodies often fail to provide therapeutic benefit in receptor-positive patients due to rapid endocytosis of antibody-bound cell surface receptors. High dose co-administration of prochlorperazine (PCZ) inhibits endocytosis and sensitises tumours to mAbs by inhibiting dynamin II but can also introduce neurological side effects. We examined the potential to use PEGylated liposomal formulations of PCZ (LPCZ) to retain the anti-cancer effects of PCZ, but limit brain uptake. Uncharged liposomes showed complete drug encapsulation and pH-dependent drug release, but cationic liposomes showed limited drug encapsulation and lacked pH-dependent drug release. Uncharged LPCZ showed comparable inhibition of EGFR internalisation to free PCZ in KJD cells. After IV administration to rats, LPCZ reduced the plasma clearance and brain uptake of PCZ compared to IV PCZ. The results suggest that LPCZ may offer some benefit over PCZ as an adjunct therapy in cancer patients receiving mAb treatment.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963424000029/pdfft?md5=d9885184d3ca15297423f751a561d6e6&pid=1-s2.0-S1549963424000029-main.pdf","citationCount":"0","resultStr":"{\"title\":\"A PEGylated liposomal formulation of prochlorperazine that limits brain exposure but retains dynamin II activity: A potential adjuvant therapy for cancer patients receiving chemotherapeutic mAbs\",\"authors\":\"Christopher N. Subasic ,&nbsp;Fiona Simpson ,&nbsp;Rodney F. Minchin ,&nbsp;Lisa M. Kaminskas\",\"doi\":\"10.1016/j.nano.2024.102733\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Anti-cancer monoclonal antibodies often fail to provide therapeutic benefit in receptor-positive patients due to rapid endocytosis of antibody-bound cell surface receptors. High dose co-administration of prochlorperazine (PCZ) inhibits endocytosis and sensitises tumours to mAbs by inhibiting dynamin II but can also introduce neurological side effects. We examined the potential to use PEGylated liposomal formulations of PCZ (LPCZ) to retain the anti-cancer effects of PCZ, but limit brain uptake. Uncharged liposomes showed complete drug encapsulation and pH-dependent drug release, but cationic liposomes showed limited drug encapsulation and lacked pH-dependent drug release. Uncharged LPCZ showed comparable inhibition of EGFR internalisation to free PCZ in KJD cells. After IV administration to rats, LPCZ reduced the plasma clearance and brain uptake of PCZ compared to IV PCZ. The results suggest that LPCZ may offer some benefit over PCZ as an adjunct therapy in cancer patients receiving mAb treatment.</p></div>\",\"PeriodicalId\":19050,\"journal\":{\"name\":\"Nanomedicine : nanotechnology, biology, and medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-01-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1549963424000029/pdfft?md5=d9885184d3ca15297423f751a561d6e6&pid=1-s2.0-S1549963424000029-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nanomedicine : nanotechnology, biology, and medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1549963424000029\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanomedicine : nanotechnology, biology, and medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1549963424000029","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

摘要

由于与抗体结合的细胞表面受体的快速内吞作用,抗癌单克隆抗体往往无法为受体阳性患者带来治疗效果。大剂量联合使用丙氯苯嗪(PCZ)可抑制内吞,并通过抑制动态胺 II 使肿瘤对 mAbs 敏感,但也会带来神经系统副作用。我们研究了使用 PCZ 的 PEG 化脂质体制剂(LPCZ)的可能性,以保留 PCZ 的抗癌效果,但限制脑部吸收。不带电的脂质体显示出完全的药物包囊和pH值依赖性药物释放,而阳离子脂质体则显示出有限的药物包囊和缺乏pH值依赖性药物释放。在KJD细胞中,不带电的LPCZ对表皮生长因子受体内化的抑制作用与游离PCZ相当。大鼠静脉注射 PCZ 后,与静脉注射 PCZ 相比,LPCZ 降低了 PCZ 的血浆清除率和脑摄取量。这些结果表明,LPCZ作为一种辅助疗法,可为接受mAb治疗的癌症患者带来比PCZ更多的益处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
A PEGylated liposomal formulation of prochlorperazine that limits brain exposure but retains dynamin II activity: A potential adjuvant therapy for cancer patients receiving chemotherapeutic mAbs

Anti-cancer monoclonal antibodies often fail to provide therapeutic benefit in receptor-positive patients due to rapid endocytosis of antibody-bound cell surface receptors. High dose co-administration of prochlorperazine (PCZ) inhibits endocytosis and sensitises tumours to mAbs by inhibiting dynamin II but can also introduce neurological side effects. We examined the potential to use PEGylated liposomal formulations of PCZ (LPCZ) to retain the anti-cancer effects of PCZ, but limit brain uptake. Uncharged liposomes showed complete drug encapsulation and pH-dependent drug release, but cationic liposomes showed limited drug encapsulation and lacked pH-dependent drug release. Uncharged LPCZ showed comparable inhibition of EGFR internalisation to free PCZ in KJD cells. After IV administration to rats, LPCZ reduced the plasma clearance and brain uptake of PCZ compared to IV PCZ. The results suggest that LPCZ may offer some benefit over PCZ as an adjunct therapy in cancer patients receiving mAb treatment.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
11.10
自引率
0.00%
发文量
133
审稿时长
42 days
期刊介绍: The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
期刊最新文献
Retraction notice to “In vitro angiogenic performance and in vivo brain targeting of magnetized endothelial progenitor cells for neurorepair therapies” [Nanomedicine: Nanotechnology, Biology and Medicine 10/1 (2014) 225–234] Facile fabrication of nano-bioactive glass functionalized blended hydrogel with nucleus pulposus-derived MSCs to improve regeneration potential in treatment of disc degeneration by in vivo rat model. Micellar curcumol for maintenance therapy of ovarian cancer by activating the FOXO3a Conceptual rationale for the use of chemically modified nanocomposites for active influence on atherosclerosis using the greater omentum model of experimental animals Preparation of cubic liquid crystal nanoparticles of puerarin and its protective effect on ischemic stroke
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1