Targeted delivery of irinotecan to colon cancer cells using epidermal growth factor receptor-conjugated liposomes

Abstract Background CPT-11 (irinotecan) is one of the most efficient agents used for colorectal cancer chemotherapy. However, as for many other chemotherapeutic drugs, how to minimize the side effects of CPT-11 still needs to be thoroughly described. Objectives This study aimed to develop the CPT-11...

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Main Authors: Yongwei Liu, Xinghui Li, Renqun Pen, Wei Zuo, Ya Chen, Xiuying Sun, Juhua Gou, Qianwen Guo, Maoling Wen, Wuqi Li, Shuangjiang Yu, Hao Liu, Min Huang
Format: Article
Language:English
Published: BMC 2022-08-01
Series:BioMedical Engineering OnLine
Subjects:
Online Access:https://doi.org/10.1186/s12938-022-01012-8
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author Yongwei Liu
Xinghui Li
Renqun Pen
Wei Zuo
Ya Chen
Xiuying Sun
Juhua Gou
Qianwen Guo
Maoling Wen
Wuqi Li
Shuangjiang Yu
Hao Liu
Min Huang
author_facet Yongwei Liu
Xinghui Li
Renqun Pen
Wei Zuo
Ya Chen
Xiuying Sun
Juhua Gou
Qianwen Guo
Maoling Wen
Wuqi Li
Shuangjiang Yu
Hao Liu
Min Huang
author_sort Yongwei Liu
collection DOAJ
description Abstract Background CPT-11 (irinotecan) is one of the most efficient agents used for colorectal cancer chemotherapy. However, as for many other chemotherapeutic drugs, how to minimize the side effects of CPT-11 still needs to be thoroughly described. Objectives This study aimed to develop the CPT-11-loaded DSPE-PEG 2000 targeting EGFR liposomal delivery system and characterize its targeting specificity and therapeutic effect on colorectal cancer (CRC) cells in vitro and in vivo. Results The synthesized liposome exhibited spherical shapes (84.6 ± 1.2 nm to 150.4 nm ± 0.8 nm of estimated average sizes), good stability, sustained release, and enough drug loading (55.19%). For in vitro experiments, SW620 cells treated with CPT-11-loaded DSPE-PEG2000 targeting EGFR liposome showed lower survival extended level of intracellular ROS production. In addition, it generated an enhanced apoptotic cell rate by upregulating the protein expression of both cleaved-caspase-3 and cleaved-caspase-9 compared with those of SW620 cells treated with free CPT-11. Importantly, the xenograft model showed that both the non-target and EGFR-targeted liposomes significantly inhibited tumor growth compared to free CPT-11. Conclusions Compared with the non-target CPT-11-loaded DSPE-PEG2000 liposome, CPT-11-loaded DSPE-PEG2000 targeting EGFR liposome treatment showed much better antitumor activity in vitro in vivo. Thus, our findings provide new assets and expectations for CRC targeting therapy.
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spelling doaj.art-862fd9bbe0544c41be3451b1d41aa17c2022-12-22T04:01:49ZengBMCBioMedical Engineering OnLine1475-925X2022-08-0121111610.1186/s12938-022-01012-8Targeted delivery of irinotecan to colon cancer cells using epidermal growth factor receptor-conjugated liposomesYongwei Liu0Xinghui Li1Renqun Pen2Wei Zuo3Ya Chen4Xiuying Sun5Juhua Gou6Qianwen Guo7Maoling Wen8Wuqi Li9Shuangjiang Yu10Hao Liu11Min Huang12Department of Infection, Rongchang District People’s Hospital of ChongqingDepartment of Digestion, Rongchang District People’s Hospital of ChongqingDepartment of Digestion, Rongchang District People’s Hospital of ChongqingDepartment of Digestion, Rongchang District People’s Hospital of ChongqingDepartment of Digestion, Rongchang District People’s Hospital of ChongqingDepartment of Digestion, Rongchang District People’s Hospital of ChongqingDepartment of Digestion, Rongchang District People’s Hospital of ChongqingDepartment of Digestion, Rongchang District People’s Hospital of ChongqingDepartment of Digestion, Rongchang District People’s Hospital of ChongqingDepartment of Digestion, Rongchang District People’s Hospital of ChongqingDepartment of Neurosurgery, The First Hospital Affiliated to Army Military Medical University (Southwest Hospital)Department of Digestion, Rongchang District People’s Hospital of ChongqingDepartment of Digestion, The Affiliated Hospital of North Sichuan Medical CollegeAbstract Background CPT-11 (irinotecan) is one of the most efficient agents used for colorectal cancer chemotherapy. However, as for many other chemotherapeutic drugs, how to minimize the side effects of CPT-11 still needs to be thoroughly described. Objectives This study aimed to develop the CPT-11-loaded DSPE-PEG 2000 targeting EGFR liposomal delivery system and characterize its targeting specificity and therapeutic effect on colorectal cancer (CRC) cells in vitro and in vivo. Results The synthesized liposome exhibited spherical shapes (84.6 ± 1.2 nm to 150.4 nm ± 0.8 nm of estimated average sizes), good stability, sustained release, and enough drug loading (55.19%). For in vitro experiments, SW620 cells treated with CPT-11-loaded DSPE-PEG2000 targeting EGFR liposome showed lower survival extended level of intracellular ROS production. In addition, it generated an enhanced apoptotic cell rate by upregulating the protein expression of both cleaved-caspase-3 and cleaved-caspase-9 compared with those of SW620 cells treated with free CPT-11. Importantly, the xenograft model showed that both the non-target and EGFR-targeted liposomes significantly inhibited tumor growth compared to free CPT-11. Conclusions Compared with the non-target CPT-11-loaded DSPE-PEG2000 liposome, CPT-11-loaded DSPE-PEG2000 targeting EGFR liposome treatment showed much better antitumor activity in vitro in vivo. Thus, our findings provide new assets and expectations for CRC targeting therapy.https://doi.org/10.1186/s12938-022-01012-8Irinotecan (CPT-11)DSPE-PEG2000EGFRColorectal cancerSW620 cell
spellingShingle Yongwei Liu
Xinghui Li
Renqun Pen
Wei Zuo
Ya Chen
Xiuying Sun
Juhua Gou
Qianwen Guo
Maoling Wen
Wuqi Li
Shuangjiang Yu
Hao Liu
Min Huang
Targeted delivery of irinotecan to colon cancer cells using epidermal growth factor receptor-conjugated liposomes
BioMedical Engineering OnLine
Irinotecan (CPT-11)
DSPE-PEG2000
EGFR
Colorectal cancer
SW620 cell
title Targeted delivery of irinotecan to colon cancer cells using epidermal growth factor receptor-conjugated liposomes
title_full Targeted delivery of irinotecan to colon cancer cells using epidermal growth factor receptor-conjugated liposomes
title_fullStr Targeted delivery of irinotecan to colon cancer cells using epidermal growth factor receptor-conjugated liposomes
title_full_unstemmed Targeted delivery of irinotecan to colon cancer cells using epidermal growth factor receptor-conjugated liposomes
title_short Targeted delivery of irinotecan to colon cancer cells using epidermal growth factor receptor-conjugated liposomes
title_sort targeted delivery of irinotecan to colon cancer cells using epidermal growth factor receptor conjugated liposomes
topic Irinotecan (CPT-11)
DSPE-PEG2000
EGFR
Colorectal cancer
SW620 cell
url https://doi.org/10.1186/s12938-022-01012-8
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