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
[1]   Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of Cremophor-free, albumin-bound paclitaxel, ABI-007, compared with Cremophor-based paclitaxel [J].
Desai, N ;
Trieu, V ;
Yao, ZW ;
Louie, L ;
Ci, S ;
Yang, A ;
Tao, CL ;
De, T ;
Beals, B ;
Dykes, D ;
Noker, P ;
Yao, R ;
Labao, E ;
Hawkins, M ;
Soon-Shiong, P .
CLINICAL CANCER RESEARCH, 2006, 12 (04) :1317-1324
[2]   Poly(D,L-lactide-co-glycolide)/montmorillonite nanoparticles for oral delivery of anticancer drugs [J].
Dong, YC ;
Feng, SS .
BIOMATERIALS, 2005, 26 (30) :6068-6076
[3]   Influence of particle size and dissolution conditions on the degradation properties of polylactide-co-glycolide particles [J].
Dunne, M ;
Corrigan, OI ;
Ramtoola, Z .
BIOMATERIALS, 2000, 21 (16) :1659-1668
[4]   Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity [J].
Fonseca, C ;
Simoes, S ;
Gaspar, R .
JOURNAL OF CONTROLLED RELEASE, 2002, 83 (02) :273-286
[5]   Bovine Serum Albumin-Based Magnetic Nanocarrier for MRI Diagnosis and Hyperthermic Therapy: A Potential Theranostic Approach Against Cancer [J].
Franchini, Mauro Comes ;
Baldi, Giovanni ;
Bonacchi, Daniele ;
Gentili, Denis ;
Giudetti, Guido ;
Lascialfari, Alessandro ;
Corti, Maurizio ;
Marmorato, Patrick ;
Ponti, Jessica ;
Micotti, Edoardo ;
Guerrini, Uliano ;
Sironi, Luigi ;
Gelosa, Paolo ;
Ravagli, Costanza ;
Ricci, Alfredo .
SMALL, 2010, 6 (03) :366-370
[6]   Size and temperature effects on poly(lactic-co-glycolic acid) degradation and microreservoir device performance [J].
Grayson, ACR ;
Cima, MJ ;
Langer, R .
BIOMATERIALS, 2005, 26 (14) :2137-2145
[7]   In vivo imaging and drug storage by quantum-dot-conjugated carbon nanotubes [J].
Guo, Yan ;
Shi, Donglu ;
Cho, Hoonsung ;
Dong, Zhongyun ;
Kulkarni, Amit ;
Pauletti, Giovanni M. ;
Wang, Wei ;
Lian, Jie ;
Liu, Wen ;
Ren, Lei ;
Zhang, Qiqing ;
Liu, Guokui ;
Huth, Christopher ;
Wang, Lumin ;
Ewing, Rodney C. .
ADVANCED FUNCTIONAL MATERIALS, 2008, 18 (17) :2489-2497
[8]   Magnetic particle hyperthermia:: nanoparticle magnetism and materials development for cancer therapy [J].
Hergt, Rudolf ;
Dutz, Silvio ;
Mueller, Robert ;
Zeisberger, Matthias .
JOURNAL OF PHYSICS-CONDENSED MATTER, 2006, 18 (38) :S2919-S2934
[9]   In vivo fluorescence imaging of the reticuloendothelial system using quantum dots in combination with bioluminescent tumour monitoring [J].
Inoue, Yusuke ;
Izawa, Kiyoko ;
Yoshikawa, Kohki ;
Yamada, Haruyasu ;
Tojo, Arinobu ;
Ohtomo, Kuni .
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 2007, 34 (12) :2048-2056
[10]   Cytotoxicity of Paclitaxel Incorporated in PLGA Nanoparticles on Hypoxic Human Tumor Cells [J].
Jin, Cheng ;
Bai, Ling ;
Wu, Hong ;
Song, Wenjie ;
Guo, Guozhen ;
Dou, Kefeng .
PHARMACEUTICAL RESEARCH, 2009, 26 (07) :1776-1784