Fluorescent, Superparamagnetic Nanospheres for Drug Storage, Targeting, and Imaging: A Multifunctional Nanocarrier System for Cancer Diagnosis and Treatment

被引:224
作者
Cho, Hoon-Sung [2 ]
Dong, Zhongyun [3 ]
Pauletti, Giovanni M. [4 ]
Zhang, Jiaming [5 ,6 ,7 ]
Xu, Hong [8 ]
Gu, Hongchen [8 ]
Wang, Lumin [5 ,6 ,7 ]
Ewing, Rodney C. [5 ,6 ,7 ]
Huth, Christopher [2 ]
Wang, Feng [2 ]
Shi, Donglu [1 ,2 ]
机构
[1] Tongji Univ, Inst Adv Mat & Nano Biomed, Shanghai 200092, Peoples R China
[2] Univ Cincinnati, Sch Energy Environm Biol & Med Engn, Cincinnati, OH 45221 USA
[3] Univ Cincinnati, Coll Med, Dept Internal Med, Cincinnati, OH 45221 USA
[4] Univ Cincinnati, James L Winkle Coll Pharm, Cincinnati, OH 45267 USA
[5] Univ Michigan, Dept Geol Sci, Ann Arbor, MI 48109 USA
[6] Univ Michigan, Dept Nucl Engn & Radiol Sci, Ann Arbor, MI 48109 USA
[7] Univ Michigan, Dept Mat Sci & Engn, Ann Arbor, MI 48109 USA
[8] Shanghai Jiao Tong Univ, Med X Inst, Shanghai 200030, Peoples R China
基金
美国国家科学基金会;
关键词
quantum dot; targeting; fluorescent imaging; drug storage; magnetic nanosphere; DELIVERY SYSTEM; PARTICLE-SIZE; NANOPARTICLES; PACLITAXEL; HYPERTHERMIA; DEGRADATION; THERAPY; POLYMERS;
D O I
10.1021/nn101000e
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
For early cancer diagnosis and treatment, a nanocarrier system is designed and developed with key components uniquely structured at nanoscale according to medical requirements. For imaging, quantum dots with emissions in the near-infrared range (similar to 800 nm) are conjugated onto the surface of a nanocomposite consisting of a spherical polystyrene matrix (similar to 150 nm) and the internally embedded, high fraction of superparamagnetic Fe3O4 nanoparticles (similar to 10 nm). For drug storage, the chemotherapeutic agent paclitaxel (PTX) is loaded onto the surfaces of these composite multifunctional nanocarriers by using a layer of biodegradable poly(lactic-co-glycolic acid) (PLGA). A cell-based cytotoxicity assay is employed to verify successful loading of pharmacologically active drug. Cell viability of human, metastatic PC3mm2 prostate cancer cells is assessed in the presence and absence of various multifunctional nanocarrier populations using the MTT assay. PTX-loaded composite nanocarriers are synthesized by conjugating anti-prostate specific membrane antigen (anti-PSMA) for targeting. Specific detection studies of anti-PSMA-conjugated nanocarrier binding activity in LNCaP prostate cancer cells are carried out. LNCaP cells are targeted successfully in vitro by the conjugation of anti-PSMA on the nanocarrier surfaces. To further explore targeting, the nanocarriers conjugated with anti-PSMA are intravenously injected into tumor-bearing nude mice. Substantial differences in fluorescent signals are observed ex vivo between tumor regions treated with the targeted nanocarrier system and the nontargeted nanocarrier system, indicating considerable targeting effects due to anti-PSMA functionalization of the nanocarriers.
引用
收藏
页码:5398 / 5404
页数:7
相关论文
共 27 条
[11]   Magnetic fluid hyperthermia (MFH):: Cancer treatment with AC magnetic field induced excitation of biocompatible superparamagnetic nanoparticles [J].
Jordan, A ;
Scholz, R ;
Wust, P ;
Fähling, H ;
Felix, R .
JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS, 1999, 201 :413-419
[12]   Paclitaxel nanoparticles for the potential treatment of brain tumors [J].
Koziara, JM ;
Lockman, PR ;
Allen, DD ;
Mumper, RJ .
JOURNAL OF CONTROLLED RELEASE, 2004, 99 (02) :259-269
[13]   Paclitaxel-loaded poly(γ-glutamic acid)-poly(lactide) nanoparticles as a targeted drug delivery system for the treatment of liver cancer [J].
Liang, HF ;
Chen, CT ;
Chen, SC ;
Kulkarni, AR ;
Chiu, YL ;
Chen, MC ;
Sung, HW .
BIOMATERIALS, 2006, 27 (09) :2051-2059
[14]   Paclitaxel-loaded gelatin nanoparticles for intravesical bladder cancer therapy [J].
Lu, Z ;
Yeh, TK ;
Tsai, M ;
Au, JLS ;
Wientjes, MG .
CLINICAL CANCER RESEARCH, 2004, 10 (22) :7677-7684
[15]  
Moghimi SM, 2001, PHARMACOL REV, V53, P283
[16]   Application of TPGS in polymeric nanoparticulate drug delivery system [J].
Mu, L ;
Seow, PH .
COLLOIDS AND SURFACES B-BIOINTERFACES, 2006, 47 (01) :90-97
[17]   Superparamagnetic nanoparticles for biomedical applications:: Possibilities and limitations of a new drug delivery system [J].
Neuberger, T ;
Schöpf, B ;
Hofmann, H ;
Hofmann, M ;
von Rechenberg, B .
JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS, 2005, 293 (01) :483-496
[18]   Paclitaxel delivery from PLGA foams for controlled release in post-surgical chemotherapy against glioblastoma multiforme [J].
Ong, Benjamin Y. S. ;
Ranganath, Sudhir H. ;
Lee, Lai Yeng ;
Lu, Fan ;
Lee, How-Sung ;
Sahinidis, Nikolaos V. ;
Wang, Chi-Hwa .
BIOMATERIALS, 2009, 30 (18) :3189-3196
[19]   Ligand-directed nanobialys as theranostic agent for drug delivery and manganese-based magnetic resonance Imaging of vascular targets [J].
Pan, Dipanjan ;
Caruthers, Shelton D. ;
Hu, Grace ;
Senpan, Angana ;
Scott, Mike J. ;
Gaffney, Patrick J. ;
Wickline, Samuel A. ;
Lanza, Gregory M. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2008, 130 (29) :9186-+
[20]   In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags [J].
Qian, Ximei ;
Peng, Xiang-Hong ;
Ansari, Dominic O. ;
Yin-Goen, Qiqin ;
Chen, Georgia Z. ;
Shin, Dong M. ;
Yang, Lily ;
Young, Andrew N. ;
Wang, May D. ;
Nie, Shuming .
NATURE BIOTECHNOLOGY, 2008, 26 (01) :83-90