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Self-assembling and self-formulating prodrug hydrogelator extends survival in a glioblastoma resection and recurrence model

文献类型：期刊论文

作者Schiapparelli, Paula1; Zhang, Pengcheng2,3,4; Lara-Velazquez, Montserrat1,5; Guerrero-Cazares, Hugo1; Lin, Ran2; Su, Hao2; Chakroun, Rami W.2; Tusa, Miguel1; Quinones-Hinojosa, Alfredo1; Cui, Honggang2,6,7,8
刊名JOURNAL OF CONTROLLED RELEASE
出版日期2020-03-10
卷号319页码:311-321
关键词Prodrug Hydrogel Glioblastoma Local therapy Chemotherapy Camptothecin
ISSN号0168-3659
DOI10.1016/j.jconrel.2020.01.003
通讯作者Quinones-Hinojosa, Alfredo(quinones-hinojosa.alfredo@mayo.edu) ; Cui, Honggang(hcui6@jhu.edu)
英文摘要Glioblastoma multiforme (GBM) is the most common and devastating type of primary brain cancer. Despite surgery and chemo/radiation therapy, recurrence often takes place and leads to patient death. We report here on the development of a camptothecin (CPT)-based self-assembling prodrug (SAPD) hydrogel that can be used as an adjunct therapy for local treatment of GBM following maximal tumor resection. When dispersed in aqueous solution, the designed CPT prodrug spontaneously assembles into supramolecular filaments with a 100% CPT loading. In both in vitro and ex vivo assays, we show that the designed CPT prodrug can be steadily released from its supramolecular filament hydrogel, effectively killing primary GBM cells derived from patients. We also found that the solution containing self-assembling CPT filaments can be directly applied to the tumor cavity after surgical removal, and forms a gel immediately upon contact with the brain tissue. Our in vivo studies with a resection and recurrence mouse model suggest that this prodrug hydrogel can release cancer therapeutics into brain parenchyma over a long period of time, suppressing tumor recurrence and leading to prolonged survival. We believe that the simplicity in prodrug design and the high efficacy in suppressing GBM growth enable the unique potential of this SAPD hydrogels for clinical translation as an adjunct therapy for GBM treatment.
WOS关键词CONVECTION-ENHANCED DELIVERY ; SUPRAMOLECULAR NANOSTRUCTURES ; SURGICAL RESECTION ; ANTITUMOR-ACTIVITY ; MALIGNANT GLIOMA ; 9L GLIOSARCOMA ; LOCAL-DELIVERY ; BRAIN-TUMORS ; RELEASE ; CAMPTOTHECIN
资助项目National Science Foundation[DMR 1255281]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000515538300023
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/281487]  
专题新药研究国家重点实验室
通讯作者Quinones-Hinojosa, Alfredo; Cui, Honggang
作者单位1.Mayo Clin, Dept Neurol Surg, Jacksonville, FL 32224 USA
2.Johns Hopkins Univ, Inst NanoBioTechnol, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA
3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
5.PECEM UNAM, Plan Combined Studies Med MD PhD Program, Mexico City, DF, Mexico
6.Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA
7.Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA
8.Johns Hopkins Univ, Wilmer Eye Inst, Ctr Nanomed, Sch Med, 400 North Broadway, Baltimore, MD 21231 USA
推荐引用方式
GB/T 7714		 Schiapparelli, Paula,Zhang, Pengcheng,Lara-Velazquez, Montserrat,et al. Self-assembling and self-formulating prodrug hydrogelator extends survival in a glioblastoma resection and recurrence model[J]. JOURNAL OF CONTROLLED RELEASE,2020,319:311-321.
APA Schiapparelli, Paula.,Zhang, Pengcheng.,Lara-Velazquez, Montserrat.,Guerrero-Cazares, Hugo.,Lin, Ran.,...&Cui, Honggang.(2020).Self-assembling and self-formulating prodrug hydrogelator extends survival in a glioblastoma resection and recurrence model.JOURNAL OF CONTROLLED RELEASE,319,311-321.
MLA Schiapparelli, Paula,et al."Self-assembling and self-formulating prodrug hydrogelator extends survival in a glioblastoma resection and recurrence model".JOURNAL OF CONTROLLED RELEASE 319(2020):311-321.

入库方式： OAI收割

来源：上海药物研究所

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