INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Zhenqian Wu,Chen Yuan,Qin Xia,Yan Qu,Han Yang,Qianming Du,Bohui Xu
Chitosan-based nanoparticles inevitably adsorb numerous proteins in the bloodstream, forming a protein corona that significantly influences their functionality. This study employed a pre-coated protein corona using cyclic Arg-Gly-Asp peptide (cRGD)-modified bovine serum albumin (BcR) to confer tumor-targeting capabilities on siVEGF-loaded chitosan-based nanoparticles (CsR/siVEGF NPs) and actively manipulated the serum protein corona composition to enhance their anti-tumor angiogenesis. Consequently, BcR effectively binds to the nanoparticles' surface, generating nanocarriers of appropriate size and stability that enhance the inhibition of endothelial cell proliferation, migration, invasion, and tube formation, as well as suppress tumor proliferation and angiogenesis in tumor-bearing nude mice. Proteomic analysis indicated a significant enrichment of serotransferrin, albumin, and proteasome subunit alpha type-1 in the protein corona of BcR-precoated NPs formed in the serum of tumor-bearing nude mice. Additionally, there was a decrease in proteins associated with complement activation, immunoglobulins, blood coagulation, and acute-phase responses. This modification resulted in an enhanced impact on anti-tumor angiogenesis, along with a reduction in opsonization and inflammatory responses. Therefore, pre-coating of nanoparticles with a functionalized albumin corona to manipulate the composition of serum protein corona emerges as an innovative approach to improve the delivery effectiveness of chitosan-based carriers for siVEGF, targeting the inhibition of tumor angiogenesis.
研究领域:
生物医学工程
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肿瘤学
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药剂学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2020
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IF 8.758
Shengyu Zhang,Ye Gan,Lanlan Shao,Tianqing Liu,Danyi Wei,Yanyan Yu,Hongwei Guo,Hongyan Zhu
Targeting vascular endothelial growth factor (VEGF) using small interfering RNA (siVEGF) has shown great potential in inhibiting the growth, proliferation, and migration of tumors by reducing the proliferation of blood vessels. On the basis of bionic principles, a novel pH-responsive and virus mimetic shell-sheddable chitosan (CS) micelles (CMs) as siRNA delivery system was introduced in this study. The cyclo(Arg-Gly-Asp-d-Phe-Lys) (cRGD) modified poly(enthylene glycol) (PEG) was conjugated to the HA2 modified chitosan via a hydrazone linkage (cRGD-PEG-Hz-CS-HA2). The cRGD-PEG-Hz-CS-HA2 conjugate could form micelles by interacting with the complex of octanal, Boc-l-lysine, and 9-d-arginine (9R) (octyl-Lys-9R) as a hydrophodic core forming agent, termed as cRGD-PEG-Hz-CS-HA2/octyl-Lys-9R (abbreviated as cRGD/HA2/Hz-CMs).The CMs modified with cRGD can accurately target glioma cells (U87MG cells) with high expression of αvβ3. The payloads of siVEGF were packed into the core of cRGD/HA2/Hz-CMs via electrostatic interaction and hydrophobic interaction. The intracellular cargo release was achieved by the pH-responsive lysis of the hydrazone bond in acidic environment of endosome. Moreover, the exposed HA2, as a pH-sensitive membrane-disruptive peptide, assists the escape of the carriers from endosome into cytosol. In addition, cRGD/HA2/Hz-CMs can effectively deliver siVEGF and silence VEGF gene expression in U87MG cells, leading to the significant tumor growth inhibition. This study demonstrates that cRGD/HA2/Hz-CMs can deliver and release siVEGF in a controlled manner, which was traced by the fluorescence resonance energy transfer (FRET) system in order to achieve RNAi-based anti-angiogenic treatment of cancer in vivo.
研究领域:
药剂学
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分子生物学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2017
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IF 3.756
Guirong Zheng,Ruirui Zhao,Aixiao Xu,Zhichun Shen,Xian Chen,Jingwei Shao
Combination with chemotherapeutic drug and gene therapy has been proven highly effective in suppressing tumor progression. Hence, an asialoglycoprotein receptor (ASGPR)-targeting nanodrug delivery system based on mesoporous silica (MSN) nanocarrier for co-delivery of sorafenib (SO) and vascular endothelial growth factor (VEGF) targeted siRNA (siVEGF) to hepatocellular carcinoma (HCC) was successfully designed and synthesized. The structure of nanoparticles was characterized by IR, particle size, zeta potential and N2 adsorption-desorption. The nanoparticles were further evaluated for drug release, cellular uptake, transfection, cell cytotoxicity and cell cycle against HepG2 and Huh7 cells. In vitro testing demonstrated that MSN-LA delivery system could not only induce S cell cycle arrest, enhance the cytotoxicity and improve the tumor target of SO and siVEGF, but also enhance the siVEGF transfection efficiency in ASGPR-overexpressing Huh7 cells. Overall, the MSN-LA delivery system can be a promising drug carrier which could further enhance the anti-cancer efficacy of SO and siVEGF via the active targeting property of LA .
研究领域:
药剂学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Nano Research
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2021
·Vol. 15
·期 2
·1455-1465
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IF 8.897
Wen Lijuan,Peng Yu,Wang Kai,Huang Zhihua,He Shiying,Xiong Ruiwen,Wu Longping,Zhang Fengtian,Hu Fuqiang
Glioblastoma (GBM) is one of the malignant brain tumors with high mortality and no curative treatments. Abnormally elevated vascular endothelial growth factor (VEGF) in GBM seriously disrupts the blood brain barrier (BBB) with an increased permeability, resulting in poor outcome and prognosis. RNAi interference has shown strong potential to inhibit VEGF expression, thus it is necessary to development an effective and safe gene delivery system possessing the ability to cross the BBB and target GBM cells. This study aims to explore the anti-GBM effect of angiopep-2 (Ap) peptide modified reactive oxygen species (ROS) cleavable thioketal (TK) linked glycolipid-like nanocarrier (CSTKSA) delivering anti-VEGF siRNA (R), termed as Ap-CSTKSA/R complexes. Ap functionalized modification produced an enhanced cellular uptake and a stronger bio-distribution of Ap-CSTKSA/R complexes in U87 MG cells and brain tumor tissues, respectively. Ap-CSTKSA/R complexes exhibited great superiority in GBM growth inhibition and finally translated into the longest survival period mainly via receptor-mediated targeting delivery, VEGF gene silencing accompanied with remarkable angiogenesis inhibition, and suppressed expression of caveolin-1 which is involved in BBB functional regulation in the occurrence and treatment of GBM. The study indicated that Ap functionalization on ROS-responsive glycolipid-like copolymer exhibits a promising and effective gene delivery platform for GBM targeted treatment.
研究领域:
肿瘤学
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神经科学
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药学
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基因治疗
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）