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
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沈阳化工大学材料科学与工程学院沈阳 110142