pH and redox triggered doxorubicin release from covalently linked carbon dots conjugates
pH and redox triggered doxorubicin release from covalently linked carbon dots conjugates
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DOI：
10.1039/d0nr08381j
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发表时间：
2021-03-14
期刊：
影响因子：
6.7
通讯作者：
Leblanc, Roger M.
中科院分区：
文献类型：
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作者：
Hettiarachchi, Sajini D.;Cilingir, Emel Kirbas;Leblanc, Roger M.
肿瘤微环境响应型给药系统是降低大剂量化疗药物急性毒性的潜在途径。尽管传统的纳米药物递送系统，氧化还原和pH刺激的药物递送系统目前正在获得关注。因此，目前的研究旨在比较三种不同的共价碳点（C-dots）系统的基础上阿霉素（dox）的释放曲线和癌细胞活力在酸性和生理条件下的功效。在本研究中检查的C-点纳米系统是直接缀合的（C-点-dox）、pH触发的（C-点-HBA-dox）和氧化还原刺激的（C-点-S-S-dox）缀合物。C-dots-S-S-dox、C-dots-HBA-dox和C-dots-dox的载药含量（DLC%）分别为34.2 +/-0.4、60.0 +/-0.3和70.0 +/-0.2%，其通过UV-vis光谱分析检测。强调了dox释放范例，所有三种缀合物在酸性pH下比在生理pH下更快地从C-dots中释放dox。在酸性介质中，通过pH刺激，C-dots-HBA-dox缀合物获得的最高dox释放百分比为74.6 +/- 0.8%。当引入氧化还原诱导剂二硫苏糖醇（DTT）时，优先地，氧化还原刺激C-dot-S-S-dox缀合物在酸性pH下比在pH 7.4下表现出更快的dox释放。SJGBM 2细胞活力实验显示，在人工酸化的pH 6.4培养基中，pH刺激物C-dots-HBA-dox缀合物显示出显著的细胞活力下降。在生理pH条件下，氧化还原刺激物C-dots-S-S-dox偶联物的细胞存活率比pH刺激物C-dots-HBA-dox的细胞存活率高60%，但在人工酸化的pH 6.4条件下，其效果略有下降。此外，目前的研究表明，刺激缀合物的显着效果比直接酰胺键的药物缓释。
Tumor microenvironment responsive drug delivery systems are potential approaches to reduce the acute toxicity caused by high-dose cancer chemotherapy. Notwithstanding the conventional nano-drug delivery systems, the redox and pH stimuli drug delivery systems are currently gaining attention. Therefore, the current study was designed to compare three different covalent carbon dots (C-dots) systems based on doxorubicin (dox) release profiles and cancer cell viability efficacy under acidic and physiological conditions. The C-dots nanosystems that were examined in this study are directly conjugated (C-dots-dox), pH triggered (C-dots-HBA-dox), and the redox stimuli (C-dots-S-S-dox) conjugates. The drug loading content (DLC%) of the C-dots-S-S-dox, C-dots-HBA-dox, and C-dots-dox was 34.2 +/- 0.4, 60.0 +/- 0.3, and 70.0 +/- 0.2%, respectively, that examined by UV-vis spectral analysis. The dox release paradigms were emphasized that all three conjugates were promisingly released the dox from C-dots faster in acidic pH than in physiological pH. The displayed highest dox released percentage in the acidic medium was 74.6 +/- 0.8% obtained by the pH stimuli, C-dots-HBA-dox conjugate. When introducing the redox inducer, dithiothreitol (DTT), preferentially, the redox stimuli C-dot-S-S-dox conjugate demonstrated a faster dox release at acidic pH than in the pH 7.4. The SJGBM2 cell viability experiments revealed that the pH stimuli, C-dots-HBA-dox conjugate, displayed a significant cell viability drop in the artificially acidified pH 6.4 medium. However, in the physiological pH, the redox stimuli, C-dots-S-S-dox conjugate, was promising over the pH stimuli C-dots-HBA-dox, exhibiting cell viability of 60%, though its' efficacy dropped slightly in the artificially acidified pH 6.4 medium. Moreover, the current study illustrates the stimuli conjugates' remarkable efficacy on sustain drug release than direct amide linkage.