Biodegradable nanoparticles sequentially decorated with Polyethyleneimine and Hyaluronan for the targeted delivery of docetaxel to airway cancer cells.
Biodegradable nanoparticles sequentially decorated with Polyethyleneimine and Hyaluronan for the targeted delivery of docetaxel to airway cancer cells.
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DOI：
10.1186/s12951-015-0088-2
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发表时间：
2015-04-03
影响因子：
10.2
通讯作者：
Quaglia F
中科院分区：
文献类型：
--
作者：
Maiolino S;Russo A;Pagliara V;Conte C;Ungaro F;Russo G;Quaglia F
新型聚合物纳米粒(NPs)是专门为在体内输送化疗药物而设计的，旨在提高治疗活性和选择性，涵盖了纳米医学领域的一个非常相关的领域。在这里，我们描述了如何通过静电作用在可生物降解的聚(乳酸-乙醇酸)纳米粒(PLGA)上构建透明质酸(HA)和聚乙烯亚胺(PEI)的聚合物壳，从而获得具有独特特征的纳米粒，该纳米粒具有持续输送多西紫杉醇(DTX)药物以及改善细胞内摄取的独特特征。通过仔细选择层合条件，可以得到稳定的PEI或HA/PEI壳层。NPS在盐和富含蛋白质的介质中具有极好的稳定性，尺寸和表面电荷符合静脉注射的生物学要求，并具有DTX的缓释作用。检测PLGA/PEI/HA和PLGA/PEI纳米粒在CD44(+)(A549)和CD44(−)(CALU-3)肺癌细胞中的细胞毒性、摄取和活性。事实上，由于透明质酸酶在肿瘤间质中过度表达，表面透明质酸降解/解离后可形成PEI包被的纳米粒。PLGA/PEI/HA和PLGA/PEI纳米粒对两种细胞的细胞毒作用均无统计学意义，提示PEI在NP壳中的引入不受其固有毒性的影响。罗丹明(Rho)荧光标记的NPs(Rho-PLGA/PEI/HA和Rho-PLGA/PEI NPs)在A549细胞内的转运显示，与CALU-3细胞相比，只有Rho-PLGA/PEI/HA NPs的摄取增加，且具有时间依赖性。正如预期的那样，A549细胞对Rho-PLGA/PEI NP的摄取与在CALU-3细胞中观察到的相似。Rho-PLGA/PEI/HA纳米粒在A549细胞中有较好的核周定位。对A549细胞的细胞毒性实验表明，通过PLGA/PEI/HA纳米粒传递的DTX比游离DTX具有更强的抗增殖活性。此外，作为透明质酸酶介导的肿瘤间质降解的假说结果，DTX-PLGA/PEI纳米粒仍然能够提高游离DTX的细胞毒活性。综上所述，结果引导我们假设，包被PEI/HA外壳的可生物降解纳米粒代表着一种非常有前途的治疗CD44过表达肺癌的系统。原则上，这种新型的纳米载体可以利用壳和核的性质扩展到不同的单一药物和药物组合。本文的在线版本(doi：10.1186/s12951-0150088-2)包含补充材料，授权用户可以使用。
Novel polymeric nanoparticles (NPs) specifically designed for delivering chemotherapeutics in the body and aimed at improving treatment activity and selectivity, cover a very relevant area in the field of nanomedicine. Here, we describe how to build a polymer shell of Hyaluronan (HA) and Polyethyleneimine (PEI) on biodegradable NPs of poly(lactic-co-glycolic) acid (PLGA) through electrostatic interactions and to achieve NPs with unique features of sustained delivery of a docetaxel (DTX) drug cargo as well as improved intracellular uptake. A stable PEI or HA/PEI shell could be obtained by careful selection of layering conditions. NPs with exquisite stability in salt and protein-rich media, with size and surface charge matching biological requirements for intravenous injection and endowed with sustained DTX release could be obtained. Cytotoxicity, uptake and activity of both PLGA/PEI/HA and PLGA/PEI NPs were evaluated in CD44(+) (A549) and CD44(−) (Calu-3) lung cancer cells. In fact, PEI-coated NPs can be formed after degradation/dissociation of the surface HA because of the excess hyaluronidases overexpressed in tumour interstitium. There was no statistically significant cytotoxic effect of PLGA/PEI/HA and PLGA/PEI NPs in both cell lines, thus suggesting that introduction of PEI in NP shell was not hampered by its intrinsic toxicity. Intracellular trafficking of NPs fluorescently labeled with Rhodamine (RHO) (RHO-PLGA/PEI/HA and RHO-PLGA/PEI NPs) demonstrated an increased time-dependent uptake only for RHO-PLGA/PEI/HA NPs in A549 cells as compared to Calu-3 cells. As expected, RHO-PLGA/PEI NP uptake in A549 cells was comparable to that observed in Calu-3 cells. RHO-PLGA/PEI/HA NPs internalized into A549 cells showed a preferential perinuclear localization. Cytotoxicity data in A549 cells suggested that DTX delivered through PLGA/PEI/HA NPs exerted a more potent antiproliferative activity than free DTX. Furthermore, DTX-PLGA/PEI NPs, as hypothetical result of hyaluronidase-mediated degradation in tumor interstitium, were still able to improve the cytotoxic activity of free DTX. Taken together, results lead us to hypothesize that biodegradable NPs coated with a PEI/HA shell represent a very promising system to treat CD44 overexpressing lung cancer. In principle, this novel nanocarrier can be extended to different single drugs and drug combinations taking advantage of the shell and core properties. The online version of this article (doi:10.1186/s12951-015-0088-2) contains supplementary material, which is available to authorized users.
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影响因子：
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作者：
Esposito D;Crescenzi E;Sagar V;Loreni F;Russo A;Russo G
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影响因子：
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