Automatic target-seeking nanoparticle inhibiting orthotopic drug-resistant colon cancer and liver metastases via regulating cancer cell adhesion and proliferation

Abstract Galectin-3 (Gal-3) plays an important role in adhesion and proliferation of cancer cells. The level of Gal-3 in blood and the expression of Gal-3 in colon cancer tissue are significantly increased in patient with colon cancer. The elevated Gal-3 promotes the migration and drug resistance of...

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Main Authors: Shaobo Bai, Yang Sun, Miao Liu, Ying Cheng, Qifeng Ji, Bangle Zhang, Zhifu Yang, Siyuan Zhou, Daozhou Liu
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Nanobiotechnology
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Online Access:https://doi.org/10.1186/s12951-025-03422-x
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author Shaobo Bai
Yang Sun
Miao Liu
Ying Cheng
Qifeng Ji
Bangle Zhang
Zhifu Yang
Siyuan Zhou
Daozhou Liu
author_facet Shaobo Bai
Yang Sun
Miao Liu
Ying Cheng
Qifeng Ji
Bangle Zhang
Zhifu Yang
Siyuan Zhou
Daozhou Liu
author_sort Shaobo Bai
collection DOAJ
description Abstract Galectin-3 (Gal-3) plays an important role in adhesion and proliferation of cancer cells. The level of Gal-3 in blood and the expression of Gal-3 in colon cancer tissue are significantly increased in patient with colon cancer. The elevated Gal-3 promotes the migration and drug resistance of colon cancer. Therefore, Gal-3 is a promising target to inhibit the growth and metastases of cancer cells. Besides, integrin αvβ3, a receptor of Gal-3, is highly expressed in colon cancer cell and blood vessel in colon cancer tissue. In this paper, an automatic target-seeking nanoparticle (SP@MCaP) contained siGal-3 and paris saponin VII (PSVII) was prepared. In vivo, by automatically capturing Gal-3 in the blood circulation, SP@MCaP actively recognized cancer tissue vessel and drug-resistant colon cancer cells with elevated integrin αvβ3 expression, resulting in specifical accumulation in orthotopic drug-resistant colon cancer tissue. SP@MCaP diminished Gal-3 level in serum and orthotopic drug-resistant colon cancer tissue, and then suppressed the proliferation of drug-resistant colon cancer cells. Importantly, SP@MCaP reconstructed the adhesion of drug-resistant colon cancer cells and reversed the immunosuppressive microenvironment in orthotopic drug-resistant colon cancer tissue and liver tissue. Finally, under the synergistic effect of siGal-3 and PSVII, SP@MCaP successfully inhibited the growth of orthotopic drug-resistant colon cancer and its liver metastases. In a word, this paper explored a novel concept of the active co-delivery of siGal-3 and PSVII by modification of nanoparticle, which holds promise for targeted therapy in orthotopic drug-resistant colon cancer and its liver metastases. Graphical abstract First, SP@MCaP automatically captured Gal-3 in the blood, actively recognized cancer tissue vessel and drug-resistant colon cancer cells with elevated integrin αvβ3 expression and specifically accumulated in orthotopic drug-resistant colon cancer tissue. Then, SP@MCaP successfully inhibited the growth of orthotopic drug-resistant colon cancer and its liver metastases by diminishing Gal-3 level in serum and orthotopic drug-resistant colon cancer tissue, suppressing the proliferation of drug-resistant colon cancer cells, reconstructing the adhesion of drug-resistant colon cancer cells and ameliorating the immunosuppressive microenvironment in orthotopic drug-resistant colon cancer tissue and liver tissue
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institution DOAJ
issn 1477-3155
language English
publishDate 2025-06-01
publisher BMC
record_format Article
series Journal of Nanobiotechnology
spelling doaj-art-207555dd6a4a4e1d8068c6c72203b9c22025-08-20T03:10:40ZengBMCJournal of Nanobiotechnology1477-31552025-06-0123112010.1186/s12951-025-03422-xAutomatic target-seeking nanoparticle inhibiting orthotopic drug-resistant colon cancer and liver metastases via regulating cancer cell adhesion and proliferationShaobo Bai0Yang Sun1Miao Liu2Ying Cheng3Qifeng Ji4Bangle Zhang5Zhifu Yang6Siyuan Zhou7Daozhou Liu8Department of Pharmaceutics, School of Pharmacy, Air Force Medical UniversityKey Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Air Force Medical UniversityDepartment of Pharmaceutics, School of Pharmacy, Air Force Medical UniversityDepartment of Pharmaceutics, School of Pharmacy, Air Force Medical UniversityDepartment of Pharmaceutics, School of Pharmacy, Air Force Medical UniversityDepartment of Pharmaceutics, School of Pharmacy, Air Force Medical UniversityDepartment of Pharmacy, Xijing Hospital, Air Force Medical UniversityDepartment of Pharmaceutics, School of Pharmacy, Air Force Medical UniversityDepartment of Pharmaceutics, School of Pharmacy, Air Force Medical UniversityAbstract Galectin-3 (Gal-3) plays an important role in adhesion and proliferation of cancer cells. The level of Gal-3 in blood and the expression of Gal-3 in colon cancer tissue are significantly increased in patient with colon cancer. The elevated Gal-3 promotes the migration and drug resistance of colon cancer. Therefore, Gal-3 is a promising target to inhibit the growth and metastases of cancer cells. Besides, integrin αvβ3, a receptor of Gal-3, is highly expressed in colon cancer cell and blood vessel in colon cancer tissue. In this paper, an automatic target-seeking nanoparticle (SP@MCaP) contained siGal-3 and paris saponin VII (PSVII) was prepared. In vivo, by automatically capturing Gal-3 in the blood circulation, SP@MCaP actively recognized cancer tissue vessel and drug-resistant colon cancer cells with elevated integrin αvβ3 expression, resulting in specifical accumulation in orthotopic drug-resistant colon cancer tissue. SP@MCaP diminished Gal-3 level in serum and orthotopic drug-resistant colon cancer tissue, and then suppressed the proliferation of drug-resistant colon cancer cells. Importantly, SP@MCaP reconstructed the adhesion of drug-resistant colon cancer cells and reversed the immunosuppressive microenvironment in orthotopic drug-resistant colon cancer tissue and liver tissue. Finally, under the synergistic effect of siGal-3 and PSVII, SP@MCaP successfully inhibited the growth of orthotopic drug-resistant colon cancer and its liver metastases. In a word, this paper explored a novel concept of the active co-delivery of siGal-3 and PSVII by modification of nanoparticle, which holds promise for targeted therapy in orthotopic drug-resistant colon cancer and its liver metastases. Graphical abstract First, SP@MCaP automatically captured Gal-3 in the blood, actively recognized cancer tissue vessel and drug-resistant colon cancer cells with elevated integrin αvβ3 expression and specifically accumulated in orthotopic drug-resistant colon cancer tissue. Then, SP@MCaP successfully inhibited the growth of orthotopic drug-resistant colon cancer and its liver metastases by diminishing Gal-3 level in serum and orthotopic drug-resistant colon cancer tissue, suppressing the proliferation of drug-resistant colon cancer cells, reconstructing the adhesion of drug-resistant colon cancer cells and ameliorating the immunosuppressive microenvironment in orthotopic drug-resistant colon cancer tissue and liver tissuehttps://doi.org/10.1186/s12951-025-03422-xDrug-resistant colon cancerGalectin-3Cell adhesionParis saponin VIIIntegrin αvβ3
spellingShingle Shaobo Bai
Yang Sun
Miao Liu
Ying Cheng
Qifeng Ji
Bangle Zhang
Zhifu Yang
Siyuan Zhou
Daozhou Liu
Automatic target-seeking nanoparticle inhibiting orthotopic drug-resistant colon cancer and liver metastases via regulating cancer cell adhesion and proliferation
Journal of Nanobiotechnology
Drug-resistant colon cancer
Galectin-3
Cell adhesion
Paris saponin VII
Integrin αvβ3
title Automatic target-seeking nanoparticle inhibiting orthotopic drug-resistant colon cancer and liver metastases via regulating cancer cell adhesion and proliferation
title_full Automatic target-seeking nanoparticle inhibiting orthotopic drug-resistant colon cancer and liver metastases via regulating cancer cell adhesion and proliferation
title_fullStr Automatic target-seeking nanoparticle inhibiting orthotopic drug-resistant colon cancer and liver metastases via regulating cancer cell adhesion and proliferation
title_full_unstemmed Automatic target-seeking nanoparticle inhibiting orthotopic drug-resistant colon cancer and liver metastases via regulating cancer cell adhesion and proliferation
title_short Automatic target-seeking nanoparticle inhibiting orthotopic drug-resistant colon cancer and liver metastases via regulating cancer cell adhesion and proliferation
title_sort automatic target seeking nanoparticle inhibiting orthotopic drug resistant colon cancer and liver metastases via regulating cancer cell adhesion and proliferation
topic Drug-resistant colon cancer
Galectin-3
Cell adhesion
Paris saponin VII
Integrin αvβ3
url https://doi.org/10.1186/s12951-025-03422-x
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