Co-Delivery of Gemcitabine and Honokiol by Lipid Bilayer-Coated Mesoporous Silica Nanoparticles Enhances Pancreatic Cancer Therapy via Targeting Depletion of Tumor Stroma

Sep 21, 2026

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Syndecan-1 (SDC1) modified lipid bilayer (LB)-coated mesoporous silica nanoparticles (MSN) were designed to co-deliver gemcitabine (GEM) and honokiol (HNK) for targeted pancreatic cancer therapy. Encapsulation efficiencies for GEM and HNK in SDC1-LB-MSN-GEM/HNK were 60.3 ± 3.2% and 73.0 ± 1.1%. Targeting efficiency was evaluated in BxPC-3 cells, showing a 2-fold fluorescence increase due to SDC1/IGF1R-mediated endocytosis, accompanied by markedly enhanced cytotoxicity. Mechanistic studies indicated SDC1-LB-MSN-HNK induced tumor apoptosis via the mitochondrial pathway, and in BALB/c nude mice it achieved tumor growth inhibition of 56.19%, outperforming free GEM/HNK and LB-MSN-GEM/HNK groups, with preliminary safety supported.

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molecules Article Co-Delivery of Gemcitabine and Honokiol by Lipid Bilayer-Coated Mesoporous Silica Nanoparticles Enhances Pancreatic Cancer Therapy via Targeting Depletion of Tumor Stroma Dan Liu, Linjiang Wang, Henan Li, Dong Li, Jianwen Zhou, Jing Wang, Qi Zhang * and Defu Cai * Citation: Liu, D.; Wang, L.; Li, H.; Li, D.; Zhou, J.; Wang, J.; Zhang, Q.; Cai, D. Co-Delivery of Gemcitabine and Honokiol by Lipid Bilayer-Coated Mesoporous Silica Nanoparticles Enhances Pancreatic Cancer Therapy via Targeting Depletion of Tumor Stroma. Molecules 2024, 29, 675 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)molecules29030675 Academic Editor: Fabio Sonvico Received: 15 January 2024 Revised: 29 January 2024 Accepted: 30 January 2024 Published: 31 January 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar 161006, China; [liudan@qmu.edu.cn](liudan@qmu.edu.cn) (D.L.); [lingjiangwang6@gmail.com](lingjiangwang6@gmail.com) (L.W.); [henanli0902@gmail.com](henanli0902@gmail.com) (H.L.); [lidong201809@gmail.com](lidong201809@gmail.com) (D.L.); [zhoujianwen@qmu.edu.cn](zhoujianwen@qmu.edu.cn) (J.Z.); [wangjing@qmu.edu.cn](wangjing@qmu.edu.cn) (J.W.) * Correspondence: [zhangqi@qmu.edu.cn](zhangqi@qmu.edu.cn) (Q.Z.); [cai@qmu.edu.cn](cai@qmu.edu.cn) (D.C.) Abstract: Syndecan-1 (SDC1) modified lipid bilayer (LB)-coated mesoporous silica nanoparticles (MSN) to co-deliver gemcitabine (GEM) and honokiol (HNK) were prepared for the targeting treatment of pancreatic cancer. The encapsulation efficiencies of GEM and HNK in SDC1-LB-MSNGEM/HNK were determined to be 60.3 ± 3.2% and 73.0 ± 1.1% . The targeting efficiency of SDC1-LB-MSN-GEM/HNK was investigated in BxPC-3 cells in vitro. The fluorescence intensity in the cells treated with SDC1-LB-MSN-Cou6 was 2-fold of LB-MSN-Cou6-treated cells, which was caused by SDC1/IGF1R-mediated endocytosis. As anticipated, its cytotoxicity was significantly increased. Furthermore, the mechanism was verified that SDC1-LB-MSN-HNK induced tumor cell apoptosis through the mitochondrial apoptosis pathway. Finally, the biodistribution, tumor growth inhibition, and preliminary safety studies were performed on BALB/c nude mice bearing BxPC-3 tumor models. The tumor growth inhibition index of SDC1-LB-MSN-GEM/HNK was 56.19%, which was 1.45-fold and 1.33-fold higher than that of the free GEM/HNK and LB-MSN-GEM/HNK treatment groups, respectively. As a result, SDC1-LB-MSN-GEM/HNK combined advantages of both GEM and HNK and simultaneously targeted and eliminated pancreatic cancerous and cancer-associated stromal cells. In summary, the present study demonstrated a new strategy of synergistic GEM and HNK to enhance the therapeutic effect of pancreatic cancer via the targeting depletion of tumor stroma. Keywords: gemcitabine; honokiol; lipid bilayer-coated mesoporous silica nanoparticles; syndecan-1; targeting tumor stroma 1. Introduction Gemcitabine (GEM), a nucleoside analogue, is a first-line chemotherapy drug for pancreatic cancer. However, the median survival was 6.8 months and the objective response rate was 9.4% for GEM-treated patients [1] . The reason for the worse prognosis of pancreatic cancer in clinic is the resistance to GEM [2] . This resistance resulted mainly from the stroma of pancreatic cancer in which tumor cell clusters are wrapped by a dense, interconnected stromal structure, creating physical barriers to prevent GEM from penetrating and accumulating in the tumor cells [3,4] . Insufficient activation or rapid inactivation may lead to unfavorable GEM pharmacok

FAQs

What delivery system was used to co-deliver gemcitabine and honokiol?

Syndecan-1 modified lipid bilayer-coated mesoporous silica nanoparticles (SDC1-LB-MSN) were prepared to co-deliver gemcitabine (GEM) and honokiol (HNK).

How was targeting efficiency evaluated in vitro?

Targeting efficiency was investigated in BxPC-3 cells by measuring fluorescence intensity, where SDC1/IGF1R-mediated endocytosis increased intracellular fluorescence about 2-fold versus LB-MSN controls.

What therapeutic effects were observed in vivo and how did they compare to other treatments?

In BALB/c nude mice bearing BxPC-3 tumors, SDC1-LB-MSN-GEM/HNK produced a tumor growth inhibition index of 56.19%, which was higher than free GEM/HNK (1.45-fold) and LB-MSN-GEM/HNK (1.33-fold), with preliminary safety also assessed.

Sep 21, 2026

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