Preparation of DSPE-PEG-cRGD Modified Cationic Liposomes for Delivery of OC-2 shRNA and The Antitumor Effects on Breast Cancer

Cationic liposome delivery of interfering RNA (shRNA) plays an important role in tumor therapy. The cyclic Arg-Gly-Asp (cRGD) modified cationic liposomes (cRGD-CL) were designed for targeted delivery of ONECUT2 (OC-2) shRNA (pshOC-2) to breast cancer cells. The characterization analysis of cationic...

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Main Authors: Chunyan Liu, Wenli Zhao, Ligang Zhang, Huamin Sun, Xi Chen, Ning Deng
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/14/10/2157
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author Chunyan Liu
Wenli Zhao
Ligang Zhang
Huamin Sun
Xi Chen
Ning Deng
author_facet Chunyan Liu
Wenli Zhao
Ligang Zhang
Huamin Sun
Xi Chen
Ning Deng
author_sort Chunyan Liu
collection DOAJ
description Cationic liposome delivery of interfering RNA (shRNA) plays an important role in tumor therapy. The cyclic Arg-Gly-Asp (cRGD) modified cationic liposomes (cRGD-CL) were designed for targeted delivery of ONECUT2 (OC-2) shRNA (pshOC-2) to breast cancer cells. The characterization analysis of cationic liposome showed that the prepared cRGD-CL/pshOC-2 lipoplexes had uniform particle size (150 ± 1.02 nm), moderate zeta potential (19.8 ± 0.249 mV) and high encapsulation efficiency (up to 96%). The results of flow cytometer showed that the introduction of cRGD could significantly promote the liposomes targeting tumor cells. In MCF-7 cells, the pshOC-2 could down-regulate expression of OC-2 and result in cell apoptosis, inhibition of the wound healing, migration and cell colony formation, in which the signal pathways of Bcl-xL, Bcl-2 were inhibited and the signal pathways of Bax and Cleaved Caspase-3 were promoted. In MCF-7 xenograft mice, intravenous administration of cRGD-CL/pshOC-2 lipoplexes could effectively reduce the expression of OC-2 in tumors and result in apparently antitumor effects, which suggested that the lipoplexes might be deeply penetrated into tumor through receptor-mediated transcytosis. The results revealed that the cationic liposome (cRGD-CL) was an effective delivery system for OC-2 shRNA, which might be an effective therapeutic candidate for breast cancer.
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spelling doaj.art-496fc1d55adc4eccb5391dfff05d31412023-11-24T01:57:12ZengMDPI AGPharmaceutics1999-49232022-10-011410215710.3390/pharmaceutics14102157Preparation of DSPE-PEG-cRGD Modified Cationic Liposomes for Delivery of OC-2 shRNA and The Antitumor Effects on Breast CancerChunyan Liu0Wenli Zhao1Ligang Zhang2Huamin Sun3Xi Chen4Ning Deng5Guangdong Province Engineering Research Center for Antibody Drug and Immunoassay, Department of Biology, Jinan University, Guangzhou 510000, ChinaGuangdong Province Engineering Research Center for Antibody Drug and Immunoassay, Department of Biology, Jinan University, Guangzhou 510000, ChinaGuangdong Province Engineering Research Center for Antibody Drug and Immunoassay, Department of Biology, Jinan University, Guangzhou 510000, ChinaGuangdong Province Engineering Research Center for Antibody Drug and Immunoassay, Department of Biology, Jinan University, Guangzhou 510000, ChinaGuangdong Province Engineering Research Center for Antibody Drug and Immunoassay, Department of Biology, Jinan University, Guangzhou 510000, ChinaGuangdong Province Engineering Research Center for Antibody Drug and Immunoassay, Department of Biology, Jinan University, Guangzhou 510000, ChinaCationic liposome delivery of interfering RNA (shRNA) plays an important role in tumor therapy. The cyclic Arg-Gly-Asp (cRGD) modified cationic liposomes (cRGD-CL) were designed for targeted delivery of ONECUT2 (OC-2) shRNA (pshOC-2) to breast cancer cells. The characterization analysis of cationic liposome showed that the prepared cRGD-CL/pshOC-2 lipoplexes had uniform particle size (150 ± 1.02 nm), moderate zeta potential (19.8 ± 0.249 mV) and high encapsulation efficiency (up to 96%). The results of flow cytometer showed that the introduction of cRGD could significantly promote the liposomes targeting tumor cells. In MCF-7 cells, the pshOC-2 could down-regulate expression of OC-2 and result in cell apoptosis, inhibition of the wound healing, migration and cell colony formation, in which the signal pathways of Bcl-xL, Bcl-2 were inhibited and the signal pathways of Bax and Cleaved Caspase-3 were promoted. In MCF-7 xenograft mice, intravenous administration of cRGD-CL/pshOC-2 lipoplexes could effectively reduce the expression of OC-2 in tumors and result in apparently antitumor effects, which suggested that the lipoplexes might be deeply penetrated into tumor through receptor-mediated transcytosis. The results revealed that the cationic liposome (cRGD-CL) was an effective delivery system for OC-2 shRNA, which might be an effective therapeutic candidate for breast cancer.https://www.mdpi.com/1999-4923/14/10/2157OC-2breast cancercRGDcationic liposomesshRNA
spellingShingle Chunyan Liu
Wenli Zhao
Ligang Zhang
Huamin Sun
Xi Chen
Ning Deng
Preparation of DSPE-PEG-cRGD Modified Cationic Liposomes for Delivery of OC-2 shRNA and The Antitumor Effects on Breast Cancer
Pharmaceutics
OC-2
breast cancer
cRGD
cationic liposomes
shRNA
title Preparation of DSPE-PEG-cRGD Modified Cationic Liposomes for Delivery of OC-2 shRNA and The Antitumor Effects on Breast Cancer
title_full Preparation of DSPE-PEG-cRGD Modified Cationic Liposomes for Delivery of OC-2 shRNA and The Antitumor Effects on Breast Cancer
title_fullStr Preparation of DSPE-PEG-cRGD Modified Cationic Liposomes for Delivery of OC-2 shRNA and The Antitumor Effects on Breast Cancer
title_full_unstemmed Preparation of DSPE-PEG-cRGD Modified Cationic Liposomes for Delivery of OC-2 shRNA and The Antitumor Effects on Breast Cancer
title_short Preparation of DSPE-PEG-cRGD Modified Cationic Liposomes for Delivery of OC-2 shRNA and The Antitumor Effects on Breast Cancer
title_sort preparation of dspe peg crgd modified cationic liposomes for delivery of oc 2 shrna and the antitumor effects on breast cancer
topic OC-2
breast cancer
cRGD
cationic liposomes
shRNA
url https://www.mdpi.com/1999-4923/14/10/2157
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