Multifunctional Lipid-Based Nanoparticles for Codelivery of Anticancer Drugs and siRNA for Treatment of Non-Small Cell Lung Cancer with Different Level of Resistance and EGFR Mutations.
Multifunctional Lipid-Based Nanoparticles for Codelivery of Anticancer Drugs and siRNA for Treatment of Non-Small Cell Lung Cancer with Different Level of Resistance and EGFR Mutations.
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DOI：
10.3390/pharmaceutics13071063
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发表时间：
2021-07-11
期刊：
影响因子：
5.4
通讯作者：
Minko T
中科院分区：
文献类型：
--
作者：
Majumder J;Minko T
对化疗的抗性、增强的增殖、侵袭、血管生成和转移（RPIAM）代表限制癌症治疗功效的主要障碍，尤其是在癌症的晚期阶段。克服或抑制RPIAM可以显着改善治疗结果。非小细胞肺癌（NSCLC）通常在晚期被诊断出，并且通常具有对化疗的内在耐药性，伴随着治疗期间获得性耐药性的快速发展。致癌受体酪氨酸激酶（TK），特别是表皮生长因子（EGF）TK，在MAPK/PI 3 K/Akt/STAT通路的激活中起重要作用，最终导致RPIAM的发生。然而，不同药物对EGF-TK的抑制受到各种防御机制和突变的限制。为了有效地预防NSCLC中RPIAM的发展，我们配制并测试了多组分和多功能癌症靶向递送系统，其含有纳米结构脂质载体（NLC）作为载体，促黄体生成素释放激素（LHRH）作为癌症靶向部分，EFG-TK抑制剂吉非替尼和/或紫杉醇作为抗癌药物，靶向EGF受体（EGFR）mRNA的siRNA作为EGF受体的抑制剂，和用于癌细胞可视化的成像剂（罗丹明）。获得的实验数据表明，这种复杂的传递系统具有显着增强的抗癌活性，不能通过单独应用的单个组件实现。
Resistance to chemotherapy, enhanced proliferation, invasion, angiogenesis, and metastasis (RPIAM) represent major obstacles that limit the efficacy of cancer treatment especially in advanced stages of cancer. Overcoming or suppressing RPIAM can dramatically improve the treatment outcome. Non-small cell lung cancer (NSCLC) is frequently diagnosed in an advanced stage and often possesses intrinsic resistance to chemotherapy accompanied by the fast development of acquired resistance during the treatment. Oncogenic receptor tyrosine kinases (TKs), specifically epidermal growth factor (EGF) TKs, play an important role in the activation of MAPK/PI3K/Akt/STAT pathways, finally leading to the development of RPIAM. However, the suppression of EGF-TK by different drugs is limited by various defensive mechanisms and mutations. In order to effectively prevent the development of RPIAM in NSCLC, we formulated and tested a multicomponent and multifunctional cancer targeted delivery system containing Nanostructured Lipid Carriers (NLCs) as vehicles, luteinizing hormone release hormone (LHRH) as a cancer targeting moiety, EFG-TK inhibitor gefitinib and/or paclitaxel as anticancer drug(s), siRNA targeted to EGF receptor (EGFR) mRNA as a suppressor of EGF receptors, and an imaging agent (rhodamine) for the visualization of cancer cells. Experimental data obtained show that this complex delivery system possesses significantly enhanced anticancer activity that cannot be achieved by individual components applied separately.
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影响因子：
16.1
作者：
Lai, Samuel K.;Wang, Ying-Ying;Hanes, Justin
通讯作者：
Hanes, Justin
影响因子：
3.1
作者：
Han L;Sheng B;Zeng Q;Yao W;Jiang Q
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Jiang Q
DOI：
10.1016/j.ejpb.2011.07.015
发表时间：
2012-01-01
影响因子：
4.9
作者：
Cirri, M.;Bragagni, M.;Mura, P.
通讯作者：
Mura, P.
影响因子：
10.8
作者：
Dharap, SS;Qiu, B;Minko, T
通讯作者：
Minko, T
DOI：
10.1073/pnas.0504274102
发表时间：
2005-09-06
影响因子：
11.1
作者：
Dharap, SS;Wang, Y;Minko, T
通讯作者：
Minko, T