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The role of critical micellization concentration in efficacy and toxicity of supramolecular polymers

文献类型：期刊论文

作者Su, Hao1,2; Wang, Feihu1,2; Ran, Wei3,4; Zhang, Weijie1,2,5; Dai, Wenbing1,2,6; Wang, Han1,2; Anderson, Caleb F.1,2; Wang, Zongyuan1,2,7; Zheng, Chao3,4; Zhang, Pengcheng3,4
刊名PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
出版日期2020-03-03
卷号117期号:9页码:4518-4526
关键词critical micellization concentration molecular assembly supramolecular polymers drug delivery prodrugs
ISSN号0027-8424
DOI10.1073/pnas.1913655117
通讯作者Cui, Honggang(hcui6@jhu.edu)
英文摘要The inception and development of supramolecular chemistry have provided a vast library of supramolecular structures and materials for improved practice of medicine. In the context of therapeutic delivery, while supramolecular nanostructures offer a wide variety of morphologies as drug carriers for optimized targeting and controlled release, concerns are often raised as to how their morphological stability and structural integrity impact their in vivo performance. After intravenous (i.v.) administration, the intrinsic reversible and dynamic feature of supramolecular assemblies may lead them to dissociate upon plasma dilution to a concentration below their critical micellization concentration (CMC). As such, CMC represents an important characteristic for supramolecular biomaterials design, but its pharmaceutical role remains elusive. Here, we report the design of a series of self-assembling prodrugs (SAPDs) that spontaneously associate in aqueous solution into supramolecular polymers (SPs) with varying CMCs. Two hydrophobic camptothecin (CPT) molecules were conjugated onto oligoethyleneglycol (OEG)-decorated segments with various OEG repeat numbers (2, 4, 6, 8). Our studies show that the lower the CMC, the lower the maximum tolerated dose (MTD) in rodents. When administrated at the same dosage of 10 mg/kg (CPT equivalent), SAPD 1, the one with the lowest CMC, shows the best efficacy in tumor suppression. These observations can be explained by the circulation and dissociation of SAPD SPs and the difference in molecular and supramolecular distribution between excretion and organ uptake. We believe these findings offer important insight into the role of supramolecular stability in determining their therapeutic index and in vivo efficacy.
WOS关键词DRUG-DELIVERY ; BIOLOGICAL MEDIA ; NILE RED ; PHASE-I ; MICELLES ; DESIGN ; NANOSTRUCTURES ; CAMPTOTHECIN ; ASSEMBLIES ; IRINOTECAN
资助项目National Science Foundation CAREER Award[DMR-1255281] ; National Natural Science Foundation of China[8167808]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000518473500020
出版者NATL ACAD SCIENCES
源URL[http://119.78.100.183/handle/2S10ELR8/281185]  
专题新药研究国家重点实验室
通讯作者Cui, Honggang
作者单位1.Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA
2.Johns Hopkins Univ, Inst NanoBioTechnol, Baltimore, MD 21218 USA
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
5.Zhengzhou Univ, Affiliated Hosp 1, Dept Oncol, Zhengzhou 450052, Peoples R China
6.Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing 100191, Peoples R China
7.Tianjin Univ, Sch Chem Engn & Technol, Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300072, Peoples R China
8.Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Ctr Nanomed, Baltimore, MD 21231 USA
9.Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA
10.Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA
推荐引用方式
GB/T 7714		 Su, Hao,Wang, Feihu,Ran, Wei,et al. The role of critical micellization concentration in efficacy and toxicity of supramolecular polymers[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2020,117(9):4518-4526.
APA Su, Hao.,Wang, Feihu.,Ran, Wei.,Zhang, Weijie.,Dai, Wenbing.,...&Cui, Honggang.(2020).The role of critical micellization concentration in efficacy and toxicity of supramolecular polymers.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,117(9),4518-4526.
MLA Su, Hao,et al."The role of critical micellization concentration in efficacy and toxicity of supramolecular polymers".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 117.9(2020):4518-4526.

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来源：上海药物研究所

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