pH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery.
pH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery.
复制标题
用于细胞内阿霉素递送的 pH 响应电荷反转聚合物功能化氮化硼纳米球
DOI：
10.2147/ijn.s153476
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发表时间：
2018
影响因子：
8
通讯作者：
Nakanishi H
中科院分区：
文献类型：
--
作者：
Feng S;Zhang H;Zhi C;Gao XD;Nakanishi H
背景技术能够响应生理刺激并在肿瘤细胞内有效释放药物的抗癌药物递送系统（DDS）对于有效的癌症治疗是非常需要的。在此，制备了 pH 响应型、电荷反转聚（盐酸烯丙胺）-柠康酸酐 (PAH-cit) 功能化氮化硼纳米球 (BNNS)，并将其用作将阿霉素 (DOX) 递送和控制释放到癌细胞中的载体。方法通过化学气相沉积法合成BNNS，然后用合成的电荷反转PAH-cit聚合物进行功能化。 DOX@PAH-cit-BNNS 复合物是通过逐步静电相互作用制备的，并进行了充分表征。通过共聚焦激光扫描显微镜观察癌细胞内 DOX@PAH-cit-BNNS 复合物的细胞摄取和 DOX 释放。使用 CCK-8 和活/死活力/细胞毒性测定检查 DOX@ PAH-cit-BNNS 的体外抗癌活性。结果 PAH-cit-BNNS 复合物对正常细胞和癌细胞无毒，浓度高达 100 µg/mL。 DOX 高效负载于 PAH-cit-BNNS 复合物上。在中性环境中，DOX@PAH-cit-BNNS 是稳定的，而由于 PAH-cit 的酰胺水解，负载的 DOX 在低 pH 条件下从这些复合物中有效释放。共聚焦显微镜显示癌细胞对 DOX@PAH-cit-BNNS 复合物的细胞摄取增强以及 DOX 在癌细胞核中的释放。此外，DOX 有效递送和释放到癌细胞的细胞核中导致了高治疗效率。结论 我们的研究结果表明，新开发的 PAH-cit-BNNS 复合物有望作为一种有效的 pH 响应型 DDS 用于癌症治疗。
Background Anticancer drug-delivery systems (DDSs) capable of responding to the physiological stimuli and efficiently releasing drugs inside tumor cells are highly desirable for effective cancer therapy. Herein, pH-responsive, charge-reversal poly(allylamine hydrochlorid)−citraconic anhydride (PAH-cit) functionalized boron nitride nanospheres (BNNS) were fabricated and used as a carrier for the delivery and controlled release of doxorubicin (DOX) into cancer cells. Methods BNNS was synthesized through a chemical vapor deposition method and then functionalized with synthesized charge-reversal PAH-cit polymer. DOX@PAH-cit–BNNS complexes were prepared via step-by-step electrostatic interactions and were fully characterized. The cellular uptake of DOX@PAH-cit–BNNS complexes and DOX release inside cancer cells were visualized by confocal laser scanning microscopy. The in vitro anticancer activity of DOX@ PAH-cit–BNNS was examined using CCK-8 and live/dead viability/cytotoxicity assay. Results The PAH-cit–BNNS complexes were nontoxic to normal and cancer cells up to a concentration of 100 µg/mL. DOX was loaded on PAH-cit–BNNS complexes with high efficiency. In a neutral environment, the DOX@PAH-cit–BNNS was stable, whereas the loaded DOX was effectively released from these complexes at low pH condition due to amide hydrolysis of PAH-cit. Enhanced cellular uptake of DOX@PAH-cit–BNNS complexes and DOX release in the nucleus of cancer cells were revealed by confocal microscopy. Additionally, the effective delivery and release of DOX into the nucleus of cancer cells led to high therapeutic efficiency. Conclusion Our findings indicated that the newly developed PAH-cit–BNNS complexes are promising as an efficient pH-responsive DDS for cancer therapy.