Theranostics 2020; 10(9):4073-4087. doi:10.7150/thno.41382 This issue Cite

Research Paper

All-stage precisional glioma targeted therapy enabled by a well-designed D-peptide

Danni Ran1*, Jianfen Zhou1*, Zhilan Chai1, Jinyang Li1, Cao Xie1, Jiani Mao1, Linwei Lu2, Yanyu Zhang1, Sunyi Wu1, Changyou Zhan1,3, Weiyue Lu1,2,4✉

1. Department of Pharmaceutics, School of Pharmacy, Fudan University, and Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education and PLA, Shanghai 201203, & State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
2. Department of Integrative Medicine, Huashan Hospital, and Institutes of Integrative Medicine of Fudan University, Shanghai 200041, China.
3. Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, & State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200433, China.
4. Minhang Branch, Zhongshan Hospital and Institute of Fudan-Minghang Academic Health System, Minghang Hospital, Fudan University, Shanghai 201199, China.
*These authors contributed equally to this work.

Citation:
Ran D, Zhou J, Chai Z, Li J, Xie C, Mao J, Lu L, Zhang Y, Wu S, Zhan C, Lu W. All-stage precisional glioma targeted therapy enabled by a well-designed D-peptide. Theranostics 2020; 10(9):4073-4087. doi:10.7150/thno.41382. https://www.thno.org/v10p4073.htm
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Abstract

Graphic abstract

Uncontrollable cell proliferation and irreversible neurological damage make glioma one of the most deadly diseases in clinic. Besides the multiple biological barriers, glioma stem cells (GSCs) that are responsible for the maintenance and recurrence of tumor tissues also hinder the therapeutic efficacy of chemotherapy. Therefore, all-stage precisional glioma targeted therapy regimens that could efficiently deliver drugs to glioma cells and GSCs after overcoming multiple barriers have received increasing scrutiny.

Methods: A polymeric micelle-based drug delivery system was developed by modifying a “Y-shaped” well-designed ligand of both GRP78 protein and quorum sensing receptor to achieve all-stage precisional glioma targeting, then we evaluated the targeting ability and barrier penetration ability both in vitro and in vivo. In order to achieve all-stage precisional therapy, we need kill both GSCs and glioma related cells. Parthenolide (PTL) has been investigated for its selective toxicity to glioma stem cells while Paclitaxel (PTX) and Temozolomide (TMZ) are widely used in experimental and clinical therapy of glioma respectively. So the in vivo anti-glioma effect of combination therapy was evaluated by Kaplan-Meier survival analysis and immunohistochemical (IHC) examination of tumor tissues.

Results: The “Y-shaped” well-designed peptide, termed DWVAP, exhibited excellent glioma (and GSCs) homing and barrier penetration ability. When modified on micelle surface, DWVAP peptide significantly enhanced accumulation of micelles in brain and glioma. In addition, DWVAP micelles showed no immunogenicity and cytotoxicity, which could guarantee their safety when used in vivo. Treatment of glioma-bearing mice with PTL loaded DWVAP modified PEG-PLA micelles plus PTX loaded DWVAP modified PEG-PLA micelles or PTL loaded DWVAP modified PEG-PLA micelles plus TMZ showed improved anti-tumor efficacy in comparison to PTL and PTX loaded unmodified micelles or PTL loaded unmodified micelles plus TMZ.

Conclusion: Combination of all-stage targeting strategy and concomitant use of chemotherapeutics and stem cell inhibitors could achieve precise targeted therapy for glioma

Keywords: DWVAP, all-stage targeting, drug delivery, multiple biological barriers, glioma, glioma stem cells


Citation styles

APA
Ran, D., Zhou, J., Chai, Z., Li, J., Xie, C., Mao, J., Lu, L., Zhang, Y., Wu, S., Zhan, C., Lu, W. (2020). All-stage precisional glioma targeted therapy enabled by a well-designed D-peptide. Theranostics, 10(9), 4073-4087. https://doi.org/10.7150/thno.41382.

ACS
Ran, D.; Zhou, J.; Chai, Z.; Li, J.; Xie, C.; Mao, J.; Lu, L.; Zhang, Y.; Wu, S.; Zhan, C.; Lu, W. All-stage precisional glioma targeted therapy enabled by a well-designed D-peptide. Theranostics 2020, 10 (9), 4073-4087. DOI: 10.7150/thno.41382.

NLM
Ran D, Zhou J, Chai Z, Li J, Xie C, Mao J, Lu L, Zhang Y, Wu S, Zhan C, Lu W. All-stage precisional glioma targeted therapy enabled by a well-designed D-peptide. Theranostics 2020; 10(9):4073-4087. doi:10.7150/thno.41382. https://www.thno.org/v10p4073.htm

CSE
Ran D, Zhou J, Chai Z, Li J, Xie C, Mao J, Lu L, Zhang Y, Wu S, Zhan C, Lu W. 2020. All-stage precisional glioma targeted therapy enabled by a well-designed D-peptide. Theranostics. 10(9):4073-4087.

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