Qiaoling Zhu MD , Yajie Wang MD , Ying Huang MD , Yixuan Zi MD , Simin Yan PhD , Xianbiao Shi PhD , Jun Cai MD , Haixia Zhang MD , Jianfeng Sang PhD , Wenli Zhang PhD , Weihong Ge MD
{"title":"靶向和协同癌症治疗的生物启发低密度脂蛋白共递送系统","authors":"Qiaoling Zhu MD , Yajie Wang MD , Ying Huang MD , Yixuan Zi MD , Simin Yan PhD , Xianbiao Shi PhD , Jun Cai MD , Haixia Zhang MD , Jianfeng Sang PhD , Wenli Zhang PhD , Weihong Ge MD","doi":"10.1016/j.nano.2022.102641","DOIUrl":null,"url":null,"abstract":"<div><p>Epithelial-mesenchymal transition (EMT) is the culprit of tumor invasion and metastasis. As a critical transcription factor that induces EMT, snail is of great importance in tumor progression, and knocking down its expression by small interfering RNA (siRNA) may inhibit tumor metastasis. Herein, we developed a core-shelled bioinspired low-density lipoprotein (bio-LDL) in which snail siRNA-loaded calcium phosphate nanoparticles were wrapped as the core and doxorubicin was embedded in the outer phospholipids modified with a synthetic peptide of apoB100 targeting LDL receptor-abundant tumor cells. Bio-LDL exhibited pH-responsive release, lysosomal escape ability, enhanced cytotoxicity and apoptotic induction. Bio-LDL could significantly inhibit the expression of snail and regulate EMT-related proteins to reduce tumor migration and invasion <em>in vitro</em>. Bio-LDL also displayed favorable tumor targeting and synergistic inhibition of tumor growth and metastasis <em>in vivo</em>. Therefore, the multifunctional bio-LDL will be a promising co-delivery vector and holds potential value for clinical translation.</p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":"48 ","pages":"Article 102641"},"PeriodicalIF":4.7000,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Bioinspired low-density lipoprotein co-delivery system for targeting and synergistic cancer therapy\",\"authors\":\"Qiaoling Zhu MD , Yajie Wang MD , Ying Huang MD , Yixuan Zi MD , Simin Yan PhD , Xianbiao Shi PhD , Jun Cai MD , Haixia Zhang MD , Jianfeng Sang PhD , Wenli Zhang PhD , Weihong Ge MD\",\"doi\":\"10.1016/j.nano.2022.102641\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Epithelial-mesenchymal transition (EMT) is the culprit of tumor invasion and metastasis. As a critical transcription factor that induces EMT, snail is of great importance in tumor progression, and knocking down its expression by small interfering RNA (siRNA) may inhibit tumor metastasis. Herein, we developed a core-shelled bioinspired low-density lipoprotein (bio-LDL) in which snail siRNA-loaded calcium phosphate nanoparticles were wrapped as the core and doxorubicin was embedded in the outer phospholipids modified with a synthetic peptide of apoB100 targeting LDL receptor-abundant tumor cells. Bio-LDL exhibited pH-responsive release, lysosomal escape ability, enhanced cytotoxicity and apoptotic induction. Bio-LDL could significantly inhibit the expression of snail and regulate EMT-related proteins to reduce tumor migration and invasion <em>in vitro</em>. Bio-LDL also displayed favorable tumor targeting and synergistic inhibition of tumor growth and metastasis <em>in vivo</em>. Therefore, the multifunctional bio-LDL will be a promising co-delivery vector and holds potential value for clinical translation.</p></div>\",\"PeriodicalId\":396,\"journal\":{\"name\":\"Nanomedicine: Nanotechnology, Biology and Medicine\",\"volume\":\"48 \",\"pages\":\"Article 102641\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2023-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nanomedicine: Nanotechnology, Biology and Medicine\",\"FirstCategoryId\":\"1\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1549963422001277\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanomedicine: Nanotechnology, Biology and Medicine","FirstCategoryId":"1","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1549963422001277","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Bioinspired low-density lipoprotein co-delivery system for targeting and synergistic cancer therapy
Epithelial-mesenchymal transition (EMT) is the culprit of tumor invasion and metastasis. As a critical transcription factor that induces EMT, snail is of great importance in tumor progression, and knocking down its expression by small interfering RNA (siRNA) may inhibit tumor metastasis. Herein, we developed a core-shelled bioinspired low-density lipoprotein (bio-LDL) in which snail siRNA-loaded calcium phosphate nanoparticles were wrapped as the core and doxorubicin was embedded in the outer phospholipids modified with a synthetic peptide of apoB100 targeting LDL receptor-abundant tumor cells. Bio-LDL exhibited pH-responsive release, lysosomal escape ability, enhanced cytotoxicity and apoptotic induction. Bio-LDL could significantly inhibit the expression of snail and regulate EMT-related proteins to reduce tumor migration and invasion in vitro. Bio-LDL also displayed favorable tumor targeting and synergistic inhibition of tumor growth and metastasis in vivo. Therefore, the multifunctional bio-LDL will be a promising co-delivery vector and holds potential value for clinical translation.
期刊介绍:
Nanomedicine: Nanotechnology, Biology and Medicine (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.