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Nanocarrier anticancer drug-conjugates cause higher cellular deformations: culpable for mischief.
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-08-21 , DOI: 10.1039/d0bm00923g Narendra Kale 1 , Semonti Nandi 1 , Ashwini Patil 1 , Yuvraj Patil 2 , Shashwat Banerjee 2 , Jayant Khandare 3
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-08-21 , DOI: 10.1039/d0bm00923g Narendra Kale 1 , Semonti Nandi 1 , Ashwini Patil 1 , Yuvraj Patil 2 , Shashwat Banerjee 2 , Jayant Khandare 3
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Here we report nanocarrier–anticancer drug conjugates culpable for cellular deformations, critically evidenced through image-based analysis as a measure of karyoplasmic ratio (KR) and nuclear surface area (NSA). Multiwalled carbon nanotubes (MWCNTs) were coordinated additionally with Fe3O4 nanoparticles (NPs) to evaluate the symbiotic influence, and further conjugated to Dox for evaluating the cellular kinetics and for measuring cell deformations. Cellular entry kinetics of the CNT (CNT–Dox and CNT–Cys–Fe3O4–Dox) nanocarriers and their efficiency in nuclear localization were evaluated using cervical cancer (HeLa) cells. Of note, the Dox-bound nanocarriers showed significantly enhanced cell toxicity over the free form of the drug. CNT–Dox and CNT–Cys–Fe3O4–Dox influx occurred within 4 hours, while maximum cellular retention of Dox was observed for CNT–Dox at 24 h. However, the highest KR (∼0.51) was observed for CNT–Dox within 8 hours indicating similar cellular deformations using nanocarrier anticancer drug-conjugates to that of free Dox (KR ∼0.50) at 4 hours. In addition, we observed increased NSA at 4 h in Dox treatment whereas in the case of the Dox conjugated nanocarrier, increased NSA was noted at 8 h treatment. At 8 h exposure of HeLa cells with Dox conjugates, we observed that the cells fall into distinct regions of the morphospace with respect to KR and NSA. Conclusively, nano delivery systems considered for clinical and biomedical translations must take into account the possible negative influences imparting higher cellular deformations and secondary adverse effects over the free form of the drug.
中文翻译：
纳米载体抗癌药物共轭物可引起更高的细胞变形：可能是恶作剧。
在这里，我们报告了可导致细胞变形的纳米载体-抗癌药物共轭物，通过基于图像的分析作为核质比（KR）和核表面积（NSA）的量度得到了重要证明。多壁碳纳米管（MWCNTs）还与Fe 3 O 4纳米颗粒（NPs）配合使用以评估共生影响，并进一步与Dox偶联以评估细胞动力学和测量细胞变形。CNT（CNT–Dox和CNT–Cys–Fe 3 O 4的细胞进入动力学使用宫颈癌（HeLa）细胞评估–Dox）纳米载体及其在核定位中的效率。值得注意的是，与自由形式的药物相比，与Dox结合的纳米载体显示出明显增强的细胞毒性。CNT–Dox和CNT–Cys–Fe 3 O 4–Dox流入在4小时内发生，而CNT–Dox在24小时内观察到最大的Dox细胞滞留率。然而，在8小时内观察到CNT-Dox的最高KR（〜0.51），表明使用纳米载体抗癌药物-缀合物在4小时时的细胞变形与游离Dox（KR〜0.50）相似。另外，我们观察到在Dox处理中4h的NSA升高，而在Dox共轭纳米载体的情况下，在8h处理中NSA升高。在Hex细胞与Dox缀合物接触8小时后，我们观察到细胞相对于KR和NSA属于形态空间的不同区域。最后，
更新日期：2020-10-13
中文翻译：
纳米载体抗癌药物共轭物可引起更高的细胞变形：可能是恶作剧。
在这里，我们报告了可导致细胞变形的纳米载体-抗癌药物共轭物，通过基于图像的分析作为核质比（KR）和核表面积（NSA）的量度得到了重要证明。多壁碳纳米管（MWCNTs）还与Fe 3 O 4纳米颗粒（NPs）配合使用以评估共生影响，并进一步与Dox偶联以评估细胞动力学和测量细胞变形。CNT（CNT–Dox和CNT–Cys–Fe 3 O 4的细胞进入动力学使用宫颈癌（HeLa）细胞评估–Dox）纳米载体及其在核定位中的效率。值得注意的是，与自由形式的药物相比，与Dox结合的纳米载体显示出明显增强的细胞毒性。CNT–Dox和CNT–Cys–Fe 3 O 4–Dox流入在4小时内发生，而CNT–Dox在24小时内观察到最大的Dox细胞滞留率。然而，在8小时内观察到CNT-Dox的最高KR（〜0.51），表明使用纳米载体抗癌药物-缀合物在4小时时的细胞变形与游离Dox（KR〜0.50）相似。另外，我们观察到在Dox处理中4h的NSA升高，而在Dox共轭纳米载体的情况下，在8h处理中NSA升高。在Hex细胞与Dox缀合物接触8小时后，我们观察到细胞相对于KR和NSA属于形态空间的不同区域。最后，
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