Journal of Materials Chemistry B
·
2014
·Vol. 3
·期 1
·119-126
·
IF 0
Yinan Zhao,Shubiao Zhang,Yuan Zhang,Shaohui Cui,Huiying Chen,Defu Zhi,Yuhong Zhen,Shufen Zhang,Leaf Huang
Several novel tri-peptide cationic lipids were designed and synthesized for delivering DNA and siRNA. They have tri-lysine and tri-ornithine as headgroups, a carbamate group as a linker and 12 and 14 carbon atom alkyl groups as tails. These tri-peptide cationic lipids were prepared into cationic liposomes for the study of the physicochemical properties and gene delivery. Their particle size, zeta potential and DNA-binding were characterized to show that they were suitable for gene transfection. Further results indicate that these lipids can transfer DNA and siRNA very efficiently into NCI-H460 and Hep-2 tumor cells. The selected lipid, CDO14, was able to deliver combined siRNAs against c-Myc and VEGF for silencing distinct oncogenic pathways in lung tumors of mice, with little in vitro and in vivo toxicity.
研究领域:
药学
·
分子生物学
·
癌症研究
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产品关联
DOI
PubMed
ACS Nano
·
2023
·
IF 17.1
Fangqin Fu,Wenhao Wang,Linjing Wu,Wenhua Wang,Zhengwei Huang,Ying Huang,Chuanbin Wu,Xin Pan
Lung cancer with the highest mortality poses a great threat to human health. Ferroptosis therapy has recently been raised as a promising strategy for lung cancer treatment by boosting the reactive species (ROS) production and lipid peroxidation (LPO) accumulation intracellularly. However, the insufficient intracellular ROS level and the unsatisfactory drug accumulation in lung cancer lesions hamper the efficacy of ferroptosis therapy. Here, an inhalable biomineralized liposome LDM co-loaded with dihydroartemisinin (DHA) and pH-responsive calcium phosphate (CaP) was constructed as a ferroptosis nanoinducer for achieving Ca2+-burst-centered endoplasmic reticulum (ER) stress enhanced lung cancer ferroptosis therapy. Equipped with excellent nebulization properties, about 6.80-fold higher lung lesions drug accumulation than intravenous injection made the proposed inhalable LDM an ideal nanoplatform for lung cancer treatment. The Fenton-like reaction mediated by DHA with peroxide bridge structure could contribute to intracellular ROS production and induce ferroptosis. Assisted by DHA-mediated sarco-/endoplasmic reticulum calcium ATPase (SERCA) inhibition, the initial Ca2+ burst caused by CaP shell degradation triggered the Ca2+-mediated intense ER stress and subsequently induced mitochondria dysfunction to further boost ROS accumulation, which strengthens ferroptosis. The second Ca2+ burst occurred as a result of Ca2+ influx through ferroptotic pores on cell membranes, thus sequentially constructing the lethal “Ca2+ burst-ER stress-ferroptosis” cycle. Consequently, the Ca2+-burst-centered ER stress enhanced ferroptosis process was confirmed as a cell swelling and cell membrane disruption process driven by notable intracellular ROS and LPO accumulation. The proposed LDM showed an encouraging lung retention property and extraordinary antitumor ability in an orthotropic lung tumor murine model. In conclusion, the constructed ferroptosis nanoinducer could be a potential tailored nanoplatform for nebulization-based pulmonary delivery and underscore the application of Ca2+-burst-centered ER stress enhanced lung cancer ferroptosis therapy.
研究领域:
肿瘤学
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药学
·
生物医学工程
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分子生物学
·
治疗学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2019
·Vol. 11
·期 9
·469
·
IF 4.773
Xiaonan Li,Jinglei Wang,Shang Li,Zhaorong Liu,Zhiru Zheng,Yanzhuo Zhang
In this study, a new kind of folic acid (FA)-conjugated and chitosan (CS)-coated poloxamer 407 (P407)/poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), FCPP NPs, were prepared, and further micro-encapsulated by carboxymethyl β-glucan microcapsules (MCs) to produce a multifunctional system of NPs embedded in MCs (NEMs) for potential lung tumor-targeted delivery of gefitinib. The prepared gefitinib-loaded FCPP (GFB/FCPP) NPs showed a hydrodynamic diameter of 255.4 ± 14.5 nm and existed in an amorphous state. After encapsulation in carboxymethyl β-glucan MCs, the GFB/FCPP-based NEMs (GFB/FCPP-NEMs) also exhibited a spherical morphology with a median diameter (d50) of around 2.2 μm. After hydration, GFB/FCPP- NEMs can quickly dissociate into its primary particles, GFB/FCPP NPs. Our in vitro drug release study revealed that these GFB/FCPP-NEMs exhibited a pH-responsive prolonged release property. In addition, the cellular uptake study demonstrated that FCPP-NEMs serve as an efficient carrier to enhance the delivery of the entrapped drug into the target lung tumor cells. Moreover, the GFB/FCPP-NEMs induced a superior cytotoxic effect compared with free gefitinib. The inhibitory concentration to achieve 50% cell death (IC50) of GFB/FCPP-NEMs in A549 cells was 3.82-fold lower than that of free gefitinib. According to these results, FCPP-NEMs hold a great potential as a multifunctional and high-performance biomaterial for lung tumor targeting delivery, pH-responsive sustained release, facilitated cellular uptake, and enhanced antitumor effect of antitumor drugs, like gefitinib.Keywords:nanocomposites;controlled delivery;dual-particulate;cellular uptake;carboxymethyl β-glucan;chemotherapeutic drugs
研究领域:
药学
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生物医学工程
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药物递送系统
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纳米技术
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2021
·
IF 9.776
Hongyan Cui,Yue Wang,Lili Chen,Ming Qian,Liuwei Zhang,Xiujue Zheng,Xi Yang,Li Chen,Yan Zhao,Qixian Chen,Jingyun Wang
Molecular insights into tumorigenesis have uncovered intimate correlation of SNAI1 with tumor malignancy. Herein, to explore merits of SNAI1-knockdown in tumor therapy, we harnessed RNA interference tool (shSNAI1), together with chemotherapeutic doxorubicin . Owing to abundant hydroxyl groups , pullulan was attempted to be covalently conjugated with a multiple of functional moieties, including positively-charged oligoethylenimine components for electrostatic entrapment of polyanionic shSNAI1 and hydrophobic components for entrapment of lipophilic doxorubicin. Notably, the aforementioned covalent conjugations were tailored to be detachable in response to intracellular reducing microenvironment owing to redox disulfide linkage, thereby accounting for selective intracellular liberation of the therapeutic payloads. Moreover, the surface of nanomedicine was modified with hyaluronic acid , endowing not only excellent biocompatibilities but active tumor-targeting function due to its receptors (CD44) overexpressed on tumor cells. Subsequent investigations approved appreciably targeted co-delivery of shSNAI1 and doxorubicin into solid lung tumors via systemic administration and demonstrated critical contribution of SNAI1-knockdown in amplifying chemotherapeutic potencies.
研究领域:
癌症治疗
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纳米技术
·
分子生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）