张学农教授课题组在Scientific Reports等期刊发表研究论文

[1] CD147 monoclonal antibody mediated by chitosan nanoparticles loaded with α-hederin enhances antineoplastic activity and cellular uptake in liver cancer cells

Rong Zhu+, Chun-ge Zhang+, Yang Liu , Zhi-qiang Yuan, Wei-liang Chen, Shu-di Yang, Ji-zhao Li,  Wen-jing ZHU, Xiao-feng Zhou, Ben-gang You *,  Xue-nong Zhang *

Scientific Reports 2015, doi: 10.1038/srep17904. (SCI二区,IF= 5.578)

 

Backgroud: Targeted cancer therapy has gained increasing attention because of its high specificity, significant efficacy and minimal adverse reactions. CD147 antibody was overexpressed in liver cancer cells which could be used to obtain positive targeting and enhance antitumor activity. Hederin (Hed) is a hydrophobic drug with much adverse effects when used for treatment of liver cancer. Chitosan (CS) is a polysaccharide and can be modified to be an amphiphilic polmer which could self-assemble into micelles and be applied for delivery of hydrophobic drugs.

Objectives:To synthesize two kinds of novel biodegradable polymers, designated as α-Hed-CS-NPs and α-Hed-CS-CD147-NPs and investigate antitumor activity, competitive inhibition, cellular uptake, subcellular localization and mechanism of delivery Hed to liver tumors in vitro and in vivo.

Results: CD147 antibody was coupled with α-hed chitosan nanoparticles (α-Hed-CSNPs). α-Hed-CS-CD147-NPs were round and spherical in shape, with an average particle size of 148.23 ± 1.75 nm.α-Hed-induced cell death was mainly triggered by apoptosis. The increase in intracellular accumulation of α-Hed-CS-CD147-NPs was also related to CD147-mediated internalization through the Caveolae-dependent pathway and lysosomal escape. The higher targeting antitumor efficacy of α-Hed-CS-CD147-NPs than those α-Hed-CS-NPs was attributed to its stronger fluorescence intensity in the tumor site in nude mice.

Conclusion: A monoclonal antibody was successfully modified to prepare CS NPs loaded with antitumor drugs. Antibody-modified NPs loaded with antitumor drugscould enhance further applications through antibody–antigen specific recognition.

 

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[2] Systemic delivery of micelles loading with paclitaxel using N-succinyl-palmitoyl-chitosan decorated with cRGDyK peptide to inhibit non-small-cell lung cancer

Zhi-qiang+ Yuan, Ji-zhao Li, Yang Liu, Wei-liang Chen, Shu-di Yang, Chun-ge Zhang, Wen-jing Zhu, Xiao-feng Zhou, Chun Liu, Xue-nong Zhang

International journal of pharmaceutics, 2015, 492(1): 141-151. (SCI二区,IF 3.65)

 

In this study, cRGDyK peptide-decorated polymer micelles based on N-succinyl-palmitoyl-chitosan were prepared to deliver paclitaxel (PTX/cRGDyK-SPCS) for the targeted therapy of non-small-cell lung cancer (NSCLC). cRGDyK peptide is a ligand that provides the micelles with active target effects to tumors via specific binding integrin receptor overexpressed on tumor neovascularization and cells. PTX/cRGDyK-SPCS micelles could improve the therapeutic efficacy in vitro and in vivo by increasing cellular uptake and cytotoxicity and accumulating in the tumor region. This study demonstrated the micelles have great potential as novel carriers in delivering anti-tumor drugs.

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