Gas-blasting nanocapsules to accelerate carboplatin lysosome release and nucleus delivery for prostate cancer treatment.
Gas-blasting nanocapsules to accelerate carboplatin lysosome release and nucleus delivery for prostate cancer treatment.
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气体喷射纳米胶囊加速卡铂溶酶体释放和细胞核输送以治疗前列腺癌
DOI：
10.1016/j.ajps.2020.05.002
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发表时间：
2021-03
影响因子：
10.2
通讯作者：
Zhang N
中科院分区：
文献类型：
--
作者：
Fu S;Liang S;Jiang D;Yang R;Zhang Z;Chang L;Zhang X;Liu Y;Zhang N
为了提高卡铂（CBP）的疗效和减少严重的毒副作用，研制了一种能产生气体的纳米胶囊，以促进CBP溶酶体释放和核内转运。采用w/o/w乳化溶剂挥发法将CBP和NaHCO 3（SB）共负载于纳米胶囊中制备CBP/SB-NC。它们表现出囊泡状的球形形态，均匀的粒径和负zeta电位。以较高浓度到达肿瘤部位是CBP递送的第一步，结果表明CBP/SB-NC可以有效增加肿瘤部位的药物蓄积。体外细胞摄取实验结果表明，CBP/SB-NC比CBP溶液更有效地内化到RM-1细胞中。在RM-1细胞内化后，在酸性环境中测试了气爆释放过程。结果表明，5 mg/ml的NaHCO 3是实现pH响应的气爆释放的最佳浓度。体外释药结果显示，CBP在酸性环境（pH5.0）中的释药速度明显快于中性环境（pH7.4）（P < 0.05）。透射电镜和H+浓度变化结果表明，CBP/SB 5-NC在溶酶体酸性环境（pH 5.0）中更容易发生爆炸。爆破释放可加速CBP溶酶体向细胞质的释放。此外，细胞核递送实验结果表明CBP/SB 5-NC能促进pH触发的细胞核快速递送。Pt-DNA加合实验结果表明，CBP/SB 5-NC与DNA的结合效率高于CBP溶液。最后，体外和体内抗肿瘤效果证明CBP/SB 5-NC可以增强前列腺癌治疗的抗肿瘤活性。溶血试验和组织病理学研究显示CBP/SB 5-NC在体内外均具有良好的上级安全性。所有的结果表明CBP/SB 5-NC将是一种有效的气体爆破释放制剂，以加强前列腺癌的治疗。该方案显示了用于加速CBP释放和核递送的气体喷射纳米胶囊的递送机制。从酸性细胞器渗入CBP/SB-NC的H+与其中的NaHCO 3反应，形成CO2气泡。CO2气泡的演化通过增加内压触发壳的破裂，这可以加速CBP的释放和核的递送。
To improve therapeutic effect and reduce severely side effects of carboplatin (CBP), the gas-generating nanocapsules were developed to accelerate CBP lysosome release and nucleus delivery. CBP/SB-NC was prepared by co-loading CBP and NaHCO3 (SB) in nanocapsules using w/o/w emulsification solvent evaporation. They exhibited vesicle-like spherical morphology, uniform particle size and negative zeta potential. Reaching the tumor site with a relatively high concentration is the first step for CBP delivery and the results showed that CBP/SB-NC could effectively increase drug accumulation at tumor site. After that, the drug delivery carriers need to be internalized into tumor cells and the in vitro cellular uptake ability results showed CBP/SB-NC could be internalized into RM-1 cells more efficient than CBP solution. After internalized by RM-1 cells, the gas-blasting release process was tested in acid environment. It was demonstrated that 5 mg/ml NaHCO3 was optimal to achieve pH-responsive gas-blasting release. In vitro release results showed that CBP significantly rapid release in acid environment (pH 5.0) compared to neutral pH (pH 7.4) (P < 0.05). Meanwhile, TEM and the change of the concentration of H+ results exhibited that the explosion of CBP/SB5-NC was more easily happened in lysosome acid environment (pH 5.0). The blasting release can accelerate CBP lysosome release to cytoplasm. Furthermore, the nucleus delivery results showed CBP/SB5-NC can promote pH-triggered rapid nucleus delivery. And the results of Pt-DNA adduct assay showed that the binding efficiency between CBP and DNA of CBP/SB5-NC was higher than CBP solution. At last, in vitro and in vivo anti-tumor efficacy proved that CBP/SB5-NC could enhance anti-tumor activity for prostate cancer therapy. CBP/SB5-NC also showed superior safety in vitro and in vivo by hemolysis assay and histopathological study. All of the results demonstrate that CBP/SB5-NC would be an efficient gas-blasting release formulation to enhance prostate cancer treatment. The scheme shows the delivery mechanism of gas-blasting nanocapsules for accelerating CBP release and nucleus delivery. H+ that infiltrated the CBP/SB-NC from the acidic organelles reacted with the NaHCO3 therein, forming CO2 bubbles. The evolution of CO2 bubbles triggered the bursting of the shell by increasing the internal pressure, which can accelerate CBP release and nucleus delivery.
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影响因子：
10
作者：
Chung, Ming-Fan;Chia, Wei-Tso;Sung, Hsing-Wen
通讯作者：
Sung, Hsing-Wen
CO2 气体诱导 pH 敏感脂质体释放药物以规避阿霉素耐药细胞
影响因子：
4.9
作者：
Liu, Juan;Ma, Huili;Liang, Xing-Jie
通讯作者：
Liang, Xing-Jie
影响因子：
64.8
作者：
McIlwain, H
通讯作者：
McIlwain, H
影响因子：
2.9
作者：
Xia, Hongmei;Luo, Xiaojing;Yin, Weihua
通讯作者：
Yin, Weihua
DOI：
10.1158/1078-0432.ccr-12-3791
发表时间：
2013-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Aparicio AM;Harzstark AL;Corn PG;Wen S;Araujo JC;Tu SM;Pagliaro LC;Kim J;Millikan RE;Ryan C;Tannir NM;Zurita AJ;Mathew P;Arap W;Troncoso P;Thall PF;Logothetis CJ
通讯作者：
Logothetis CJ