活性氧响应性核壳结构纳米粒子增加肿瘤富集与细胞摄取

刘芷麟; 马胜; 孙佳丽; 司星辉; 汤朝晖; 陈学思

doi:10.11777/j.issn1000-3304.2020.20066

您当前的位置：

首页 >

文章列表页 >

活性氧响应性核壳结构纳米粒子增加肿瘤富集与细胞摄取

论文 | 更新时间：2021-01-26

- 活性氧响应性核壳结构纳米粒子增加肿瘤富集与细胞摄取
- Reactive Oxygen Species Responsive Core-Shell Nanoparticles Increase Tumor Enrichment and Endocytosis
- 高分子学报 2020年51卷第10期页码：1153-1159
- 作者机构：
  
  1.中国科学院长春应用化学研究所中国科学院生态环境高分子材料重点实验室　长春 130022
  2.中国科学技术大学应用化学与工程学院　合肥 230026
- 作者简介：
  
  E-mail: ztang@ciac.ac.cn Zhao-hui Tang, E-mail: ztang@ciac.ac.cn
  E-mail: xschen@ciac.ac.cn Xue-si Chen, E-mail: xschen@ciac.ac.cn
- 基金信息：
  
  国家自然科学基金(基金号51829302, 51873206)资助项目
- DOI：10.11777/j.issn1000-3304.2020.20066
  中图分类号：
- 纸质出版日期：2020-9-1，
  
  网络出版日期：2020-7-14，
  
  收稿日期：2020-3-13，
  
  修回日期：2020-4-10，
扫描看全文
刘芷麟, 马胜, 孙佳丽, 司星辉, 汤朝晖, 陈学思. 活性氧响应性核壳结构纳米粒子增加肿瘤富集与细胞摄取[J]. 高分子学报, 2020,51(10):1153-1159.

Zhi-lin Liu, Sheng Ma, Jia-li Sun, Xing-hui Si, Zhao-hui Tang, Xue-si Chen. Reactive Oxygen Species Responsive Core-Shell Nanoparticles Increase Tumor Enrichment and Endocytosis[J]. Acta Polymerica Sinica, 2020,51(10):1153-1159.
刘芷麟, 马胜, 孙佳丽, 司星辉, 汤朝晖, 陈学思. 活性氧响应性核壳结构纳米粒子增加肿瘤富集与细胞摄取[J]. 高分子学报, 2020,51(10):1153-1159. DOI： 10.11777/j.issn1000-3304.2020.20066.

Zhi-lin Liu, Sheng Ma, Jia-li Sun, Xing-hui Si, Zhao-hui Tang, Xue-si Chen. Reactive Oxygen Species Responsive Core-Shell Nanoparticles Increase Tumor Enrichment and Endocytosis[J]. Acta Polymerica Sinica, 2020,51(10):1153-1159. DOI： 10.11777/j.issn1000-3304.2020.20066.

摘要

微环境响应性高分子纳米药物可以大幅提升药物在肿瘤部位的特异性释放，降低在正常组织泄漏而引发副作用的风险，但肿瘤细胞对聚乙二醇化纳米药物较差的摄取能力极大降低了药效. 本研究报道了一种可增强药物摄取并具有肿瘤微环境响应性的高分子模型药物递送体系，通过酯化反应得到胍基化改性罗丹明B，并将聚(L-谷氨酸)-接枝-聚(乙二醇)键合4-羟甲基苯硼酸频哪醇酯以得到ROS响应性高分子载体. 之后将胍基化罗丹明B作为模型药物用响应性高分子载体担载，得到核壳状纳米粒子PgP-HA/RhoB-Gu NPs. 体外释放与粒径变化结果表明，PgP-HA/RhoB-Gu NPs对ROS有良好的敏感响应性，细胞摄取结果表明，该胍基化罗丹明B可以更加高效被细胞摄取. 体内分布可看出纳米粒子在肿瘤部位富集明显. 通过纳米载体担载胍基化模拟药物同时实现肿瘤部位ROS响应性释放和增加细胞摄取的设计，为纳米药物更好地发挥药效提供了有效的策略.

Abstract

Tumor microenvironment responsive polymeric nanomedicines significantly improve the specific release of drugs at tumor sites

which can reduce side effects to the normal tissues. However

the poor cellular uptake ability of most PEGylated nanodrugs has reduced much of the antitumor efficacy. Therefore

it’s probably easy to imagine that after specific drug release of nanomedicines at tumor sites

the antitumor efficacy could be significantly improved with the enhancement of the drugs’ cellular uptake ability. Herein

a drug delivery system that can enhance drug endocytosis and respond to tumor microenvironment is reported. In this study

rhodamine B was bonded with arginine methyl ester to give guanidinium rhodamine B (RhoB-Gu)

and 4-(hydroxymethyl) phenylboronic acid pinacol ester (HAPE) was bonded with poly(L-glutamic acid)-graft-poly(ethylene glycol) to obtain reactive oxygen species (ROS) responsive nanocarrier

PgP-HA. Then the RhoB-Gu was loaded into PgP-HA as a model drug to obtain ROS responsive core-shell polymeric nanoparticles

PgP-HA/RhoB-Gu NPs. The nanoparticles formed a stable core-shell structure due to the electrostatic assisted hydrogen bonding between carboxyl group of PgP-HA and guanidine group of RhoB-Gu

the electrostatic interaction between tertiary amines of RhoB-Gu and carboxyl group of PgP-HA

as well as the hydrophobic interaction of HAPE segments. Furthermore

in vitro

release test showed that the PgP-HA/RhoB-Gu NPs could achieve about three fold drug accumulation release in PBS contained 1.0 mmol/L H

than in PBS without H

and the particle size also increased with the increasing concentration of H

which indicated that the PgP-HA/RhoB-Gu NPs have highly sensitive response to ROS. Meanwhile

in vivo

distribution results showed that the PgP-HA/RhoB-Gu NPs realized drug enrichment at the tumor sites

and the model drug

RhoB-Gu

showed higher cellular uptake than original RhoB

revealing good potential to expand the application on traditional chemotherapy drugs. This work provides an effective strategy of nanodrugs to improve the efficacy through ROS responsive release at tumor sites and cellular uptake increase simultaneously.

关键词

高分子纳米载体ROS敏感胞内递送

Keywords

Polymer nanocarrierReactive oxygen species responsiveIntracellular delivery

references

Ganta S, Devalapally H, Shahiwala A, Amiji M. J Control Release , 2008 . 126 ( 3 ): 187 - 204 . DOI:10.1016/j.jconrel.2007.12.017http://doi.org/10.1016/j.jconrel.2007.12.017 .

Mo R, Gu Z. Mater Today , 2016 . 19 ( 5 ): 274 - 283 . DOI:10.1016/j.mattod.2015.11.025http://doi.org/10.1016/j.mattod.2015.11.025 .

Ding Xiaoya(丁晓亚), Wang Yu(王宇), Li Gao(李杲), Xiao Chunsheng(肖春生), Chen Xuesi(陈学思). Acta Polymerica Sinica(高分子学报) , 2019 . 50 ( 5 ): 505 - 515 . DOI:10.11777/j.issn1000-3304.2019.19015http://doi.org/10.11777/j.issn1000-3304.2019.19015 .

Du J Z, Du X J, Mao C Q, Wang J. J Am Chem Soc , 2011 . 133 ( 44 ): 17560 - 17563 . DOI:10.1021/ja207150nhttp://doi.org/10.1021/ja207150n .

Gao J, Li J, Geng W C, Chen F Y, Duan X C, Zheng Z, Ding D, Guo D S. J Am Chem Soc , 2018 . 140 ( 14 ): 4945 - 4953 . DOI:10.1021/jacs.8b02331http://doi.org/10.1021/jacs.8b02331 .

Liu Z L, Tang Z H, Zhang D W, Wu J T, Si X H, Shen N, Chen X S. Sci China Mater , 2019 . 63 ( 2 ): 307 - 315.

Liu Z L, Shen N, Tang Z H, Zhang D W, Ma L L, Yang C G, Chen X S. Biomater Sci-UK , 2019 . 7 ( 7 ): 2803 - 2811 . DOI:10.1039/C9BM00002Jhttp://doi.org/10.1039/C9BM00002J .

Cheng R, Meng F H, Deng C, Klok H A, Zhong Z Y. Biomaterials , 2013 . 34 ( 14 ): 3647 - 3657 . DOI:10.1016/j.biomaterials.2013.01.084http://doi.org/10.1016/j.biomaterials.2013.01.084 .

Lee S H, Gupta M K, Bang J B, Bae H, Sung H J. Adv Healthc Mater , 2013 . 2 ( 6 ): 908 - 915 . DOI:10.1002/adhm.201200423http://doi.org/10.1002/adhm.201200423 .

Chen K, Liao S S, Guo S W, Zhang H, Cai H, Gong Q Y, Gu Z W, Luo K. Sci China Mater , 2018 . 61 ( 11 ): 1462 - 1474 . DOI:10.1007/s40843-018-9277-8http://doi.org/10.1007/s40843-018-9277-8 .

Diehn M, Cho R W, Lobo N A, Kalisky T, Dorie M J, Kulp A N, Qian D L, Lam J S, Ailles L E, Wong M Z, Joshua B, Kaplan M J, Wapnir I, Dirbas F M, Somlo G, Garberoglio C, Paz B, Shen J, Lau S K, Quake S R, Brown J M, Weissman I L, Clarke M F. Nature , 2009 . 458 ( 7239 ): 780 - 783 . DOI:10.1038/nature07733http://doi.org/10.1038/nature07733 .

Xu X D, Saw P E, Tao W, Li Y J, Ji X Y, Bhasin S, Liu Y L, Ayyash D, Rasmussen J, Huo M, Shi J J, Farokhzad O C. Adv Mater , 2017 . 29 ( 33 ): e1700141 DOI:10.1002/adma.201700141http://doi.org/10.1002/adma.201700141 .

Tapeinos C, Pandit A. Adv Mater , 2016 . 28 ( 27 ): 5553 - 5585 . DOI:10.1002/adma.201505376http://doi.org/10.1002/adma.201505376 .

Zhang Y, He P, Liu X M, Yang H L, Zhang H Y, Xiao C S, Chen X S. Biomater Sci-UK , 2019 . 7 ( 9 ): 3898 - 3905 . DOI:10.1039/C9BM00884Ehttp://doi.org/10.1039/C9BM00884E .

Xu Q H, He C L, Xiao C S, Chen X S. Macromol Biosci , 2016 . 16 ( 5 ): 635 - 646 . DOI:10.1002/mabi.201500440http://doi.org/10.1002/mabi.201500440 .

Li J J, Dirisala A, Ge Z S, Wang Y H, Yin W, Ke W D, Toh K, Xie J B, Matsumoto Y, Anraku Y, Osada K, Kataoka K. Angew Chem Int Ed , 2017 . 56 ( 45 ): 14025 - 14030 . DOI:10.1002/anie.201706964http://doi.org/10.1002/anie.201706964 .

Lee S, Baek M, Kim H Y, Ha J H, Jeoung D I. Biotechnol Lett , 2002 . 24 ( 14 ): 1147 - 1151 . DOI:10.1023/A:1016174800956http://doi.org/10.1023/A:1016174800956 .

Hartmann J T, Lipp H P. Drug Safety , 2006 . 29 ( 3 ): 209 - 230 . DOI:10.2165/00002018-200629030-00005http://doi.org/10.2165/00002018-200629030-00005 .

Weaver B A. Mol Biol Cell , 2014 . 25 ( 18 ): 2677 - 2681 . DOI:10.1091/mbc.e14-04-0916http://doi.org/10.1091/mbc.e14-04-0916 .

Park S E, Sajid M I, Parang K, Tiwari R K. Mol Pharmaceut , 2019 . 16 ( 9 ): 3727 - 3743 . DOI:10.1021/acs.molpharmaceut.9b00633http://doi.org/10.1021/acs.molpharmaceut.9b00633 .

Zhan J, Cai Y B, He S S, Wang L, Yang Z M. Angew Chem Int Ed , 2018 . 57 ( 7 ): 1813 - 1816 . DOI:10.1002/anie.201710237http://doi.org/10.1002/anie.201710237 .

Cai Y B, Shen H S, Zhan J, Lin M L, Dai L H, Ren C H, Shi Y, Liu J F, Gao J, Yang Z M. J Am Chem Soc , 2017 . 139 ( 8 ): 2876 - 2879 . DOI:10.1021/jacs.6b12322http://doi.org/10.1021/jacs.6b12322 .

Gasparini G, Bang E K, Molinard G, Tulumello D V, Ward S, Kelley S O, Roux A, Sakai N, Matile S. J Am Chem Soc , 2014 . 136 ( 16 ): 6069 - 6074 . DOI:10.1021/ja501581bhttp://doi.org/10.1021/ja501581b .

Mao L N, Wang H M, Tan M, Ou L L, Kong D L, Yang Z M. Chem Commun , 2012 . 48 ( 3 ): 395 - 397 . DOI:10.1039/C1CC16250Khttp://doi.org/10.1039/C1CC16250K .

Rothbard J B, Jessop T C, Lewis R S, Murray B A, Wender P A. J Am Chem Soc , 2004 . 126 ( 31 ): 9506 - 9507 . DOI:10.1021/ja0482536http://doi.org/10.1021/ja0482536 .

Sakai N, Futaki S, Matile S. Soft Matter , 2006 . 2 ( 8 ): 636 - 641 . DOI:10.1039/b606955jhttp://doi.org/10.1039/b606955j .

Yu H Y, Tang Z H, Li M Q, Song W T, Zhang D W, Zhang Y, Yang Y, Sun H, Deng M X, Chen X S. J Biomed Nanotechnol , 2016 . 12 ( 1 ): 69 - 78 . DOI:10.1166/jbn.2016.2152http://doi.org/10.1166/jbn.2016.2152 .

更多指标>

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

苯硼酸功能化聚合物纳米载体用于蛋白质药物胞内递送