Fluorescent, superparamagnetic nanospheres for drug storage, targeting, and imaging: a multifunctional nanocarrier system for cancer diagnosis and treatment.
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 (∼800 nm) are conjugated onto the surface of a nanocomposite consisting of a spherical polystyrene matrix (∼150 nm) and the internally embedded, high fraction of superparamagnetic Fe(3)O(4) nanoparticles (∼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.
Cho
Hoon-Sung
HS
School of Energy, Environmental, Biological and Medical Engineering, University of Cincinnati, Cincinnati, Ohio 45221, USA.
Dong
Zhongyun
Z
Pauletti
Giovanni M
GM
Zhang
Jiaming
J
Xu
Hong
H
Gu
Hongchen
H
Wang
Lumin
L
Ewing
Rodney C
RC
Huth
Christopher
C
Wang
Feng
F
Shi
Donglu
D
D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D050997:Nanomedicine / Q000379:methods*; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045663:Quantum Dots
D004337:Drug Carriers; D005456:Fluorescent Dyes; D058185:Magnetite Nanoparticles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017239:Paclitaxel