Targeted sustained delivery of antineoplastic agent with multicomponent polylactide stereocomplex micelle

Kexin Shen; Di Li; Jingjing Guan; Jianxun Ding; Zhongtang Wang; Jingkai Gu; Tongjun Liu; Xuesi Chen

doi:10.1016/j.nano.2016.12.022

Targeted sustained delivery of antineoplastic agent with multicomponent polylactide stereocomplex micelle

Nanomedicine. 2017 Apr;13(3):1279-1288. doi: 10.1016/j.nano.2016.12.022. Epub 2017 Jan 5.

Authors

Kexin Shen¹, Di Li², Jingjing Guan³, Jianxun Ding⁴, Zhongtang Wang⁵, Jingkai Gu³, Tongjun Liu⁶, Xuesi Chen²

Affiliations

¹ Jilin University, Changchun, PR China; Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, PR China.
² Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, PR China.
³ Jilin University, Changchun, PR China.
⁴ Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, PR China. Electronic address: jxding@ciac.ac.cn.
⁵ Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, PR China. Electronic address: zhongtangw@163.com.
⁶ Jilin University, Changchun, PR China. Electronic address: tongjunliu@163.com.

PMID: 28064009
DOI: 10.1016/j.nano.2016.12.022

Abstract

A c(RGDfC)-decorated polylactide stereocomplex micelle (cRGD-SCM) was prepared through the stereocomplex and hydrophobic interactions among 4-arm poly(ethylene glycol)-block-poly(D-lactide) (4-arm PEG-b-PDLA), methoxy poly(ethylene glycol)-block-poly(L-lactide) (mPEG-b-PLLA), and c(RGDfC)-poly(ethylene glycol)-block-poly(L-lactide) (cRGD-PEG-b-PLLA) for targeted treatment of α_vβ₃ integrin-positive C26 colon cancer. Doxorubicin (DOX), a model antitumor drug, was loaded into cRGD-SCM with a diameter of approximately 100nm, and the drug loading efficiency was 45.9wt.%. cRGD-SCM/DOX with a sustained release pattern exhibited prolonged circulation time, upregulated accumulation in tumor, enhanced tumor inhibition, and decreased side effects compared with free DOX and non-targeting SCM/DOX in vivo. More interestingly, the targeting ligand in the terminal of PEG can be easily replaced with other targeting groups according to the different types of malignancies. Therefore, the cRGD-decorated platform might be a promising targeted drug delivery system for personal chemotherapy clinically.

Keywords: Chemotherapy; Multicomponent micelle; Polylactide; Stereocomplex interaction; Targetability.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / administration & dosage*
Antineoplastic Agents / pharmacokinetics
Antineoplastic Agents / therapeutic use
Cell Line, Tumor
Colon / drug effects*
Colon / pathology
Colonic Neoplasms / drug therapy*
Colonic Neoplasms / pathology
Delayed-Action Preparations / chemistry*
Doxorubicin / administration & dosage*
Doxorubicin / pharmacokinetics
Doxorubicin / therapeutic use
Drug Delivery Systems
Mice
Mice, Inbred BALB C
Micelles
Peptides, Cyclic / chemistry*
Polyesters / chemistry*

Substances

Antineoplastic Agents
Delayed-Action Preparations
Micelles
Peptides, Cyclic
Polyesters
cyclic arginine-glycine-aspartic acid peptide
poly(lactide)
Doxorubicin