Citation: Zhao-hui Tang, Xue-si Chen. Tumor-targeting Drug Delivery Systems Based on Poly(_L-glutamic acid)-g-Poly(ethylene glycol)[J]. Acta Polymerica Sinica, ;2019, 50(6): 543-552. doi: 10.11777/j.issn1000-3304.2019.19036 shu

Tumor-targeting Drug Delivery Systems Based on Poly(_L-glutamic acid)-g-Poly(ethylene glycol)

Zhao-hui Tang ,
Xue-si Chen ^,

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022

Corresponding author: Xue-si Chen, xschen@ciac.ac.cn
Received Date: 21 February 2019
Revised Date: 9 April 2019
Available Online: 9 May 2019

Tumor-targeting drug delivery systems based on poly(ethylene glycol)-poly(amino acid) carriers have great potential in reducing the side effects of anticancer drugs, increasing the therapeutic index, and enhancing the druggability of drug candidates. In this work, recent progresses of our group in the tumor-targeting drug delivery systems with poly(_L-glutamic acid)-graft-poly(ethylene glycol) (PLG-g-mPEG) as carrier, are reviewed. The influence of polymer structure on the behavior of nanomedicine in vivo is discussed. Several parameters, including PLG molecular weight, mPEG/PLG weight ratio, mPEG chain length and drug loading content, have a significant influence on the plasma pharmacokinetics of the cisplatin-loaded PLG-g-mPEG nanoparticles (CDDP-NPs). The blood circulation time of the nanoparticles is prolonged with increases in PLG molecular weight, mPEG/PLG weight ratio, mPEG chain length and cisplatin loading content. Cooperative treatment concepts, such as " periphery and center” and " coagulation targeting”, are proposed. By coadministering a vascular disrupting agent (VDA) CA4P and CDDP-NPs, the CDDP-NPs mainly locates at the tumor periphery and leaves most of cancer cells at tumor center viable, the CA4P can make up defect of CDDP-NPs and efficiently kill cancer cells in tumor central regions. The " coagulation targeting” delivery platform comprises a coagulation-inducing agent and coagulation-targeted polymeric nanoparticles. As a typical VDA, DMXAA can create a unique artificial coagulation environment with additional binding sites in a solid tumor by locally activating a coagulation cascade. Coagulation-targeted cisplatin-loaded nanoparticles can selectively accumulate in the solid tumor by homing to the VDA-induced artificial coagulation environment through transglutamination. We discover that the low permeability of nanomedicine in solid tumors can significantly improve the targeting to tumor blood vessels and tumor inhibition ability of VDAs. This provides a new idea for enhancing the therapeutic effect of VDAs in tumor treatment. A powerful combinational strategy is created with nanomedicine of VDAs plus hypoxia-activated prodrugs (HAPs) for the treatment of solid tumors. The nanomedicine of VDAs can selectively enhance tumor hypoxia and boost a typical HAP tirapazamine therapy against metastatic 4T1 breast tumors.
- Poly(_L-glutamic acid),
- Tumor targeting,
- Nanomedicine,
- Cisplatin,
- Vascular disrupting agent
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Tumor-targeting Drug Delivery Systems Based on Poly(L-glutamic acid)-g-Poly(ethylene glycol)

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Tumor-targeting Drug Delivery Systems Based on Poly(_L-glutamic acid)-g-Poly(ethylene glycol)