Citation: Chang Liu, Yu-xin Chen, Jiang-fan Wang, Xuan Luo, Yu-di Huang, Jin-lei Xu, Guo-ping Yan, Si Chen, Xian-zheng Zhang. A Multi-functional Drug Delivery System Based on Dendritic Peptide for Tumor Nuclear Accurate Targeting Therapy[J]. Acta Polymerica Sinica, ;2018, 0(6): 682-691. doi: 10.11777/j.issn1000-3304.2017.17335 shu

A Multi-functional Drug Delivery System Based on Dendritic Peptide for Tumor Nuclear Accurate Targeting Therapy

1.
School of Material Science and Engineering, Wuhan Institute of Technology, Wuhan 430205
2.
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072

Corresponding author: Si Chen, chensi1989@whu.edu.cn Xian-zheng Zhang, xz-zhang@whu.edu.cn
Received Date: 25 December 2017
Revised Date: 6 February 2018
Available Online: 1 March 2018

Though chemotherapeutics has been one of the most widely used treatments for tumor therapy, it is still heavily limited due to its poor pharmacokinetics, undesirable intracellular uptake and inevitable side effects. In order to overcome these barriers, various functional groups have been introduced in drug delivery system to enhance the therapeutic efficiency of chemotherapy. In this study, a novel drug delivery system for tumor nuclear accurate targeting was designed in order to achieve precise tumor nuclear treatment. The chemotherapeutic drug (doxorubicin, DOX) was encapsulated in amphiphilic dendritic peptide with nuclear localization function to form a regular nanoparticle DD. After that, electronegative hyaluronic acid (HA) with ability of tumor targeting was coated on the surface of nanoparticle DD via electrostatic interaction to form tumor nuclear targeting drug delivery system HDD. The presence of HA endowed HDD with the tumor targeting ability and charge shielding effect, which could increase the stability of nanodrug, promote the specific internalization by tumor cells and reduce the non-specific uptake by normal tissue/cells. Furthermore, it was found that the drug delivery system HDD could realize the facile internalization by tumor cells via CD44 receptor-mediated recognition. After the degradation of HA shell by hyaluronidase (HAase) in endosome, the nuclear targeted nanodrug DD was exposed, and DOX was carried to the region of nuclear accurately by inheriting the ability from nuclear-targeted peptide. The precise targeting of drug to nuclei could be beneficial to the improvement of drug utilization as well as the suppression of tumor cells. The characteristics of this tumor nuclear accurate targeting drug delivery system, including particle sizes, zeta potential, drug loading capacity, drug release behavior, cellular uptake and antitumor efficacy, were evaluated. All of the studies confirmed that the precise tumor nuclear targeting drug delivery system HDD displayed prominent antitumor efficacy with insignificant adverse effects to normal cells in vitro, which indicated that the precise tumor nuclear targeting delivery system supplies a useful strategy for tumor therapy.
- Dendritic peptide,
- Nanodrug,
- Tumor-targeting,
- Nuclear localization,
- Precise treatment
1. [1]
  Zhang J, Yuan Z F, Wang Y, Chen W H, Luo G F, Cheng S X, Zhuo R X, Zhang X Z. J Am Chem Soc, 2013, 135: 5068-5073
2. [2]
  Li D, Tang Z M, Gao Y Q, Sun H L, Zhou S B. Adv Funct Mater, 2016, 26: 66-79
3. [3]
  Sun Q, Sun X, Ma X, Zhou Z, Jin E, Zhang B, Shen Y, van Kirk E A, Murdoch W J, Lott J R, Lodge T P, Radosz M, Lodge T P. Adv Mater, 2014, 26: 7615-7621
4. [4]
  Brannon-Peppas L, Blanchette J O. Adv Drug Delivery Rev, 2012, 64: 206-212
5. [5]
  Manzoor A A, Lindner L H, Landon C D, Park J Y, Simnick A J, Dreher M R, Das S, Hanna G, Park W, Koning G A. Cancer Res, 2012, 72: 5566-5575
6. [6]
  Cabral H, Matsumoto Y, Mizuno K, Chen Q, Murakami M, Kimura M, Terada Y, Kano M R, Miyazono K, Uesaka M, Nishiyama N, Kataoka K. Nat Nanotechnol, 2011, 6: 815-823
7. [7]
  Chang Y C, Yang K, Wei P, Huang S, Pei Y, Zhao W, Pei Z C. Angew Chem Int Ed, 2014, 53: 13126-13130
8. [8]
  Fan J X, Zheng D W, Rong L, Zhu J Y, Hong S, Li C, Xu Z S, Cheng S X, Zhang X Z. Biomaterials, 2017, 139: 116-126
9. [9]
  Jiang Q, Nie Y, Chen X B, He Y Y, Yue D, Gu Z W. Adv Funct Mater, 2017, 27(26): 1701571
10. [10]
  Yuan Y Y, Mao C Q, Du X J, Du J Z, Wang F, Wang J. Adv Mater, 2012, 24: 5476-5480
11. [11]
  Sun C Y, Shen S, Xu C F, Li H J, Liu Y, Cao Z T, Yang X Z, Xia J X, Wang J. J Am Chem Soc, 2015, 137: 15217-15224
12. [12]
  Ma S N, Zhou J, Zhang Y X, He Y Y, Jiang Q, Yue D, Xu X H, Gu Z W. ACS Appl Mater Interfaces, 2016, 8: 28468-28479
13. [13]
  Wang H X, Yang X Z, Sun C Y, Mao C Q, Zhu Y H, Wang J. Biomaterials, 2014, 35: 7622-7634
14. [14]
  Meng H, Liong M, Xia T, Li Z, Ji Z, Zink J I, Nel A E. ACS Nano, 2010, 4: 4539-4550
15. [15]
  Han M, Lv Q, Tang X J, Hu Y L, Xu D H, Li F Z, Liang W Q, Gao J Q. J Control Release, 2012, 163: 136-144
16. [16]
17. [17]
  Rajendran L, Knölker H J, Simons K. Nat Rev Drug Discov, 2010, 9: 29-42
18. [18]
  Guo X, Wei X, Jing Y T, Zhou S B. Adv Mater, 2015, 27: 6450-6456
19. [19]
  Futaki S. Adv Drug Deliver Rev, 2005, 57: 547-558
20. [20]
  Chen S, Lei Q, Qin W X, Liu L H, Zheng D W, Fan J X, Rong L, Sun Y X, Zhang X Z. Biomaterials, 2017, 117: 92-104
21. [21]
  Han S S, Li Z Y, Zhu J Y, Han K, Zeng Z Y, Hong W, Li W X, Jia H Z, Liu Y, Zhuo R X, Zhang X Z. Small, 2015, 11: 2543-2554
22. [22]
  Chen S, Fan J X, Qiu W X, Liu L H, Cheng H, Liu F, Yan G P, Zhang X Z. Macromol Rapid Commun, 2017, 38: 1700490 DOI: 10.1002/marc.201700490 doi: 10.1002/marc.201700490
23. [23]
  Lin Y X, Qiao S L, Wang Y, Zhang R X, An H W, Ma Y, Rajapaksha R P Y J, Qiao Z Y, Wang L, Wang H. ACS Nano, 2017, 11: 1826-1839
24. [24]
  Chen S, Lei Q, Li S Y, Qin S Y, Jia H Z, Cheng Y J, Zhang X Z. Biomaterials, 2016, 92: 25-35
25. [25]
  Hu J J, Hu K, Cheng Y Y. Acta Biomater. 2016, 35, 1-11.
26. [26]
  Chen S, Fan J X, Qiu W X, Liu F, Yan G P, Zeng X, Zhang X Z. J Mater Chem B, 2018, 6: 1543-1551
27. [27]
  Liu C Q, Zhang Y, Liu M, Chen Z W, Lin Y H, Li W, Cao F F, Liu Z, Ren J S, Qu X G. Biomaterials, 2017, 139: 151-162
28. [28]
  Chen S, Rong L, Lei Q, Cao P X, Qin S Y, Zheng D W, Jia H Z, Zhu J Y, Cheng S X, Zhuo R X, Zhang X Z. Biomaterials, 2016, 77: 149-163
1. [1]
  Wenjing ZHANG , Xiaoqing WANG , Zhipeng LIU . Recent developments of inorganic metal complex-based photothermal materials and their applications in photothermal therapy. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2356-2372. doi: 10.11862/CJIC.20240254
2. [2]
  Jian Li , Yu Zhang , Rongrong Yan , Kaiyuan Sun , Xiaoqing Liu , Zishang Liang , Yinan Jiao , Hui Bu , Xin Chen , Jinjin Zhao , Jianlin Shi . 高效靶向示踪钙钛矿纳米系统光电增效抗肿瘤. Acta Physico-Chimica Sinica, 2025, 41(5): 100042-. doi: 10.1016/j.actphy.2024.100042
3. [3]
  Tingting XU , Wenjing ZHANG , Yongbo SONG . Research advances of atomic precision coinage metal nanoclusters in tumor therapy. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2275-2285. doi: 10.11862/CJIC.20240229
4. [4]
  Jiahui CHEN , Tingting ZHENG , Xiuyun ZHANG , Wei LÜ . Research progress of near-infrared absorption inorganic nanomaterials in photothermal and photodynamic therapy of tumors. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2396-2414. doi: 10.11862/CJIC.20240106
5. [5]
  Shiyang He , Dandan Chu , Zhixin Pang , Yuhang Du , Jiayi Wang , Yuhong Chen , Yumeng Su , Jianhua Qin , Xiangrong Pan , Zhan Zhou , Jingguo Li , Lufang Ma , Chaoliang Tan . 铂单原子功能化的二维Al-TCPP金属-有机框架纳米片用于增强光动力抗菌治疗. Acta Physico-Chimica Sinica, 2025, 41(5): 100046-. doi: 10.1016/j.actphy.2025.100046
6. [6]
  Jiahao Zeng , Hui Chao . 诱导程序性细胞死亡的金属抗肿瘤药物研究. University Chemistry, 2025, 40(6): 145-159. doi: 10.12461/PKU.DXHX202406019
7. [7]
  Di WU , Ruimeng SHI , Zhaoyang WANG , Yuehua SHI , Fan YANG , Leyong ZENG . Construction of pH/photothermal dual-responsive delivery nanosystem for combination therapy of drug-resistant bladder cancer cell. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1679-1688. doi: 10.11862/CJIC.20240135
8. [8]
  Zhuoya WANG , Le HE , Zhiquan LIN , Yingxi WANG , Ling LI . Multifunctional nanozyme Prussian blue modified copper peroxide: Synthesis and photothermal enhanced catalytic therapy of self-provided hydrogen peroxide. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2445-2454. doi: 10.11862/CJIC.20240194
9. [9]
  Ziheng Zhuang , Xiao Xu , Kin Shing Chan . Superdrugs for Superbugs. University Chemistry, 2024, 39(9): 128-133. doi: 10.3866/PKU.DXHX202309040
10. [10]
  Yongming Guo , Jie Li , Chaoyong Liu . Green Improvement and Educational Design in the Synthesis and Characterization of Silver Nanoparticles. University Chemistry, 2024, 39(3): 258-265. doi: 10.3866/PKU.DXHX202309057
11. [11]
  Guangming YIN , Huaiyao WANG , Jianhua ZHENG , Xinyue DONG , Jian LI , Yi'nan SUN , Yiming GAO , Bingbing WANG . Preparation and photocatalytic degradation performance of Ag/protonated g-C₃N₄ nanorod materials. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1491-1500. doi: 10.11862/CJIC.20240086
12. [12]
  Xin Lv , Hongxing Zhang , Kaibo Duan , Wenhui Dai , Zhihui Wen , Wei Guo , Junsheng Hao . Lighting the Way Against Cancer: Photodynamic Therapy. University Chemistry, 2024, 39(5): 70-79. doi: 10.3866/PKU.DXHX202309090
13. [13]
  Cuiping Yang , Huiping Ding , Jinpeng Hou , Kai Li , Weiliang Tian . Reform and Exploration of “Comprehensive and Precise Process” Assessment in Chemical Engineering Principle Experimental Course. University Chemistry, 2024, 39(3): 178-190. doi: 10.3866/PKU.DXHX202309087
14. [14]
  Yufang GAO , Nan HOU , Yaning LIANG , Ning LI , Yanting ZHANG , Zelong LI , Xiaofeng LI . Nano-thin layer MCM-22 zeolite: Synthesis and catalytic properties of trimethylbenzene isomerization reaction. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1079-1087. doi: 10.11862/CJIC.20240036
15. [15]
  Yinyin Qian , Rui Xu . Utilizing VESTA Software in the Context of Material Chemistry: Analyzing Twin Crystal Nanostructures in Indium Antimonide. University Chemistry, 2024, 39(3): 103-107. doi: 10.3866/PKU.DXHX202307051
16. [16]
  Zihan Lin , Wanzhen Lin , Fa-Jie Chen . Electrochemical Modifications of Native Peptides. University Chemistry, 2025, 40(3): 318-327. doi: 10.12461/PKU.DXHX202406089
17. [17]
  Manman Jin , Zhiguo Lv , Qingtao Niu . Teaching Reformation and Case Study for “Chemical Process Development and Design” Based on “Just-in-Time” Dynamic and Accurate Matching Industrial Needs. University Chemistry, 2024, 39(11): 108-116. doi: 10.12461/PKU.DXHX202403030
18. [18]
  Siyi ZHONG , Xiaowen LIN , Jiaxin LIU , Ruyi WANG , Tao LIANG , Zhengfeng DENG , Ao ZHONG , Cuiping HAN . Targeting imaging and detection of ovarian cancer cells based on fluorescent magnetic carbon dots. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1483-1490. doi: 10.11862/CJIC.20240093
19. [19]
  Aiai WANG , Lu ZHAO , Yunfeng BAI , Feng FENG . Research progress of bimetallic organic framework in tumor diagnosis and treatment. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1825-1839. doi: 10.11862/CJIC.20240225
20. [20]
  Peng Zhan . Practice and Reflection in Training Medicinal Chemistry Graduate Students. University Chemistry, 2024, 39(6): 112-121. doi: 10.3866/PKU.DXHX202402022

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(134)
HTML views(14)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142