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学科主题: 公共卫生
题名:
A PEGylation-Free Biomimetic Porphyrin Nanoplatform for Personalized Cancer Theranostics
作者: Cui, Liyang1,2,3,4; Lin, Qiaoya1,2,5; Jin, Cheng S.1,2,6,7; Jiang, Wenlei1,2; Huang, Huang1,2; Ding, Lili1,2; Muhanna, Nidal1,2,8; Irish, Jonathan C.1,2,8; Wang, Fan4; Chen, Juan1,2; Zheng, Gang1,2,3,6,7
关键词: porphyrin ; nanoparticle ; PEGylation ; PET imaging ; multimodal imaging ; fluorescence-guided surgery ; photodynamic therapy
刊名: ACS NANO
发表日期: 2015-04-01
DOI: 10.1021/acsnano.5b01077
卷: 9, 期:4, 页:4484-4495
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
研究领域[WOS]: Chemistry ; Science & Technology - Other Topics ; Materials Science
关键词[WOS]: DENSITY-LIPOPROTEIN NANOPARTICLES ; PEPTIDE-LIPID NANOPARTICLES ; TARGETED DRUG-DELIVERY ; COMPLEMENT ACTIVATION ; PHOTODYNAMIC THERAPY ; REPEATED INJECTIONS ; SYSTEMIC DELIVERY ; CONTRAST AGENT ; GENE DELIVERY ; BRAIN-TUMORS
英文摘要:

PEGylation (PEG) is the most commonly adopted strategy to prolong nanoparticles′ vascular circulation by mitigating the reticuloendothelial system uptake. However, there remain many concerns in regards to its immunogenicity, targeting efficiency, etc., which inspires pursuit of alternate, non-PEGylated systems. We introduced here a PEG-free, porphyrin-based ultrasmall nanostructure mimicking nature lipoproteins, termed PLP, that integrates multiple imaging and therapeutic functionalities, including positron emission tomography (PET) imaging, near-infrared (NIR) fluorescence imaging and photodynamic therapy (PDT). With an engineered lipoprotein-mimicking structure, PLP is highly stable in the blood circulation, resulting in favorable pharmacokinetics and biodistribution without the need of PEG. The prompt tumor intracellular trafficking of PLP allows for rapid nanostructure dissociation upon tumor accumulation to release monomeric porphyrins to efficiently generate fluorescence and photodynamic reactivity, which are highly silenced in intact PLP, thus providing an activatable mechanism for low-background NIR fluorescence imaging and tumor-selective PDT. Its intrinsic copper-64 labeling feature allows for noninvasive PET imaging of PLP delivery and quantitative assessment of drug distribution. Using a clinically relevant glioblastoma multiforme model, we demonstrated that PLP enabled accurate delineation of tumor from surrounding healthy brain at size less than 1 mm, exhibiting the potential for intraoperative fluorescence-guided surgery and tumor-selective PDT. Furthermore, we demonstrated the general applicability of PLP for sensitive and accurate detection of primary and metastatic tumors in other clinically relevant animal models. Therefore, PLP offers a biomimetic theranostic nanoplatform for pretreatment stratification using PET and NIR fluorescence imaging and for further customized cancer management via imaging-guided surgery, PDT, or/and potential chemotherapy.

语种: 英语
项目资助者: Canadian Institutes of Health Research ; Ontario Institute for Cancer Research ; Natural Sciences and Engineering Research Council of Canada ; National Science Foundation of China ; US Army Ovarian Cancer Research Program Translational Synergistic Leverage Award ; Prostate Cancer Canada ; Canada Foundation for Innovation ; Princess Margaret Cancer Foundation ; Joey and Toby Tanenbaum/Brazilian Ball Chair in Prostate Cancer Research
WOS记录号: WOS:000353867000118
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56711
Appears in Collections:北京大学医药卫生分析中心_期刊论文

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作者单位: 1.Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5S 2J7, Canada
2.Univ Toronto, Otolaryngol Head & Neck Surg, Toronto, ON M5S 2J7, Canada
3.Univ Hlth Network, Techna Inst, Toronto, ON M5G 2M9, Canada
4.Univ Toronto, Dept Med Biophys, Toronto, ON M5S 2J7, Canada
5.Peking Univ, Med Isotopes Res Ctr, Beijing 100871, Peoples R China
6.Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada
7.Huazhong Univ Sci & Technol, Wuhan Natl Lab Optoelect, Britton Chance Ctr Biomed Photon, Wuhan 430074, Peoples R China
8.Univ Toronto, Leslie Dan Fac Pharm, Dept Pharmaceut Sci, Toronto, ON M5S 2J7, Canada

Recommended Citation:
Cui, Liyang,Lin, Qiaoya,Jin, Cheng S.,et al. A PEGylation-Free Biomimetic Porphyrin Nanoplatform for Personalized Cancer Theranostics[J]. ACS NANO,2015,9(4):4484-4495.
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