A radio-theranostic nanoparticle with high specific drug loading for cancer therapy and imaging

被引：33

作者：

Satterlee, Andrew B. ^{[1
,2
,3
,4
]}

Yuan, Hong ^{[5
]}

Huang, Leaf ^{[1
,2
,3
,4
]}

机构：

[1] Univ N Carolina, Eshelman Sch Phorm, Div Mol Pharmaceut, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Ctr Nanotechnol Drug Delivery, Chapel Hill, NC 27599 USA

[3] UNC, Chapel Hill, NC 27599 USA

[4] NCSU Joint Dept Biomed Engn, Chapel Hill, NC 27599 USA

[5] Univ N Carolina, Dept Radiol, Biomed Res Imaging Ctr, Chapel Hill, NC 27599 USA

来源：

JOURNAL OF CONTROLLED RELEASE | 2015年 / 217卷

关键词：

Cancer; Theranostic; Nanoparticle; High specific drug loading; CALCIUM-PHOSPHATE NANOPARTICLES; HUMAN PROSTATE-CANCER; GEMCITABINE MONOPHOSPHATE; CISPLATIN NANOPARTICLES; TUMOR MICROENVIRONMENT; IRRADIATED COLLAGEN; ULTRAVIOLET-LIGHT; DELIVERY; SIRNA; FIBROBLASTS;

D O I：

10.1016/j.jconrel.2015.08.048

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We have developed a theranostic nanoparticle delivering the model radionuclide Lu-177 based on the versatile lipid-calcium-phosphate (LCP) nanoparticle delivery platform. Characterization of Lu-177-LCP has shown that radionuclide loading can be increased by several orders of magnitude without affecting the encapsulation efficiency or the morphology of Lu-177-LCP, allowing consistency during fabrication and overcoming scale-up barriers typical of nanotherapeutics. The choice of Lu-177 as a model radionuclide has allowed in vivo anticancer therapy in addition to radiographic imaging via the dual decay modes of Lu-177. Tumor accumulation of Lu-177-LCP was measured using both SPECT and Cerenkov imaging modalities in live mice, and treatment with just one dose of Lu-177-LCP showed significant in vivo tumor inhibition in two subcutaneous xenograft tumor models. Microenvironment and cytotoxicity studies suggest that Lu-177-LCP inhibits tumor growth by causing apoptotic cell death via double-stranded DNA breaks while causing a remodeling of the tumor microenvironment to a more disordered and less malignant phenotype. (c) 2015 Elsevier B.V. All rights reserved.

引用

页码：170 / 182

页数：13

共 35 条

[1]

[Anonymous], ANN PHARMACOTHER

[2] More than structural cells, fibroblasts create and orchestrate the tumor microenvironment [J].

Baglole, Carolyn J. ;

Ray, Denise M. ;

Bernstein, Steven H. ;

Feldon, Steven E. ;

Smith, Terry J. ;

Sime, Patricia J. ;

Phipps, Richard P. .

IMMUNOLOGICAL INVESTIGATIONS, 2006, 35 (3-4) :297-325

[3] Anisamide-targeted stealth liposomes: A potent carrier for targeting doxorubicin to human prostate cancer cells [J].

Banerjee, R ;

Tyagi, P ;

Li, S ;

Huang, L .

INTERNATIONAL JOURNAL OF CANCER, 2004, 112 (04) :693-700

[4] A bioengineered microenvironment to quantitatively measure the tumorigenic properties of cancer-associated fibroblasts in human prostate cancer [J].

Clark, Ashlee K. ;

Taubenberger, Anna V. ;

Taylor, Renea A. ;

Niranjan, Birunthi ;

Chea, Zhen Y. ;

Zotenko, Elena ;

Sieh, Shirly ;

Pedersen, John S. ;

Norden, Sam ;

Frydenberg, Mark ;

Grummet, Jeremy P. ;

Pook, David W. ;

Stirzaker, Clare ;

Clark, Susan J. ;

Lawrence, Mitchell G. ;

Ellem, Stuart J. ;

Hutmacher, Dietmar W. ;

Risbridger, Gail P. .

BIOMATERIALS, 2013, 34 (20) :4777-4785

[5] Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer [J].

Cox, Thomas R. ;

Erler, Janine T. .

DISEASE MODELS & MECHANISMS, 2011, 4 (02) :165-178

[6] ULTRAVIOLET LIGHT-INDUCED CHANGE IN COLLAGEN MACROMOLECULES [J].

FUJIMORI, E .

BIOPOLYMERS, 1965, 3 (02) :115-+

[7] REGULATION OF ADHERENS JUNCTION PROTEIN EXPRESSION IN GROWTH-ACTIVATED 3T3 CELLS AND IN REGENERATING LIVER [J].

GLUCK, U ;

FERNANDEZ, JLR ;

PANKOV, R ;

BENZEEV, A .

EXPERIMENTAL CELL RESEARCH, 1992, 202 (02) :477-486

[8] Radioimmunotherapy of Lymphoma: Bexxar and Zevalin [J].

Goldsmith, Stanley J. .

SEMINARS IN NUCLEAR MEDICINE, 2010, 40 (02) :122-135

[9]

Grillo-Lopez Antonio J, 2002, Expert Rev Anticancer Ther, V2, P485, DOI 10.1586/14737140.2.5.485

[10] Lipid-Coated Cisplatin Nanoparticles Induce Neighboring Effect and Exhibit Enhanced Anticancer Efficacy [J].

Guo, Shutao ;

Wang, Yuhua ;

Miao, Lei ;

Xu, Zhenghong ;

Lin, C. Michael ;

Zhang, Yuan ;

Huang, Leaf .

ACS NANO, 2013, 7 (11) :9896-9904

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