Full Text | PDF

Theranostics 2018; 8(18):5088-5105. doi:10.7150/thno.26225 This issue Cite

Research Paper

Hypoxia-responsive lipid-poly-(hypoxic radiosensitized polyprodrug) nanoparticles for glioma chemo- and radiotherapy

Lei Hua^1,2,3*, Zhen Wang^1*, Liang Zhao^1*, Honglin Mao¹, Guanghui Wang⁴, Kairuo Zhang², Xuejiao Liu¹, Dongmei Wu⁵, Yuanlin Zheng⁵, Jun Lu^5✉, Rutong Yu^1,2,3✉, Hongmei Liu^1,2,3✉

1. Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, 221002, PR China;
2. Department of Neurosurgery, Brain Hospital, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, PR China;
3. Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, 221002, PR China;
4. Department of Gynaecology and Obstetrics, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, PR China;
5. Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, 221116, PR China.
^*These authors contributed equally to this work.

✉ Corresponding authors: Hongmei Liu, PhD. Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, 221002, PR China. Phone: 86-0516-85587335; Fax: 86-0516-85587335; liuhongmei816com. Rutong Yu, PhD, MD. Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, 221002, PR China. Phone: 86-0516-85587335; Fax: 86-0516-85587335; yu.rutongcom. Jun Lu, PhD. Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, 221116, PR China. Phone: 86-0516-83500348; Fax: 86-0516-83500348; lu-jun75com More

Abstract

Treatment of malignant glioma is a challenge facing cancer therapy. In addition to surgery, and chemotherapy, radiotherapy (RT) is one of the most effective modalities of glioma treatment. However, there are two crucial challenges for RT facing malignant glioma therapy: first, gliomas are known to be resistant to radiation due to their intratumoral hypoxia; second, radiosensitizers may exhibit a lack of target specificity, which may cause a lower concentration of radiosensitizers in tumors and toxic side effects in normal tissues. Thus, novel angiopep-2-lipid-poly-(metronidazoles)n (ALP-(MIs)n) hypoxic radiosensitizer-polyprodrug nanoparticles (NPs) were designed to enhance the radiosensitizing effect on gliomas.

Methods: In this study, different degrees and biodegradabilites of hypoxic radiosensitizer MIs-based polyprodrug (P-(MIs)n) were synthesized as a hydrophobic core. P-(MIs)n were mixed with DSPE-PEG2000, angiopep-2-DSPE-PEG2000 and lecithin to self-assemble ALP-(MIs)n through a single-step nanoprecipitation method. The ALP-(MIs)n encapsulate doxorubicin (DOX) (ALP-(MIs)n/DOX) and provoke the release of DOX under hypoxic conditions for glioma chemo- and radiotherapy. In vivo glioma targeting was tested in an orthotopic glioma using live animal fluorescence/bioluminescence imaging. The effect on sensitization to RT of ALP-(MIs)n and the combination of chemotherapy and RT of ALP-(MIs)n/DOX for glioma treatment were also investigated both in vitro and in vivo.

Results: ALP-(MIs)n/DOX effectively accumulated in gliomas and could reach the hypoxic glioma site after systemic in vivo administration. These ALP-(MIs)n showed a significant radiosensitizing effect on gliomas and realized combination chemotherapy and RT for glioma treatment both in vitro and in vivo.

Conclusions: In summary, we constructed a lipid-poly-(hypoxic radiosensitized polyprodrug) nanoparticles for enhancing the RT sensitivity of gliomas and achieving the combination of radiation and chemotherapy for gliomas.

Keywords: glioma, radiosensitized polyprodrug, chemo- and radiotherapy, hypoxia-responsive, blood-brain barrier

Citation styles

©2024 Ivyspring International Publisher. Terms of use