Prostate stem cell antigen-targeted nanoparticles with dual functional properties: in vivo imaging and cancer chemotherapy.
BACKGROUND
We designed dual-functional nanoparticles for in vivo application using a modified electrostatic and covalent layer-by-layer assembly strategy to address the challenge of assessment and treatment of hormone-refractory prostate cancer.


METHODS
Core-shell nanoparticles were formulated by integrating three distinct functional components, ie, a core constituted by poly(D,L-lactic-co-glycolic acid), docetaxel, and hydrophobic superparamagnetic iron oxide nanocrystals (SPIONs), a multilayer shell formed by poly(allylamine hydrochloride) and two different sized poly(ethylene glycol) molecules, and a single-chain prostate stem cell antigen antibody conjugated to the nanoparticle surface for targeted delivery.


RESULTS
Drug release profiles indicated that the dual-function nanoparticles had a sustained release pattern over 764 hours, and SPIONs could facilitate the controlled release of the drug in vitro. The nanoparticles showed increased antitumor efficiency and enhanced magnetic resonance imaging in vitro through targeted delivery of docetaxel and SPIONs to PC3M cells. Moreover, in nude mice bearing PC3M xenografts, the nanoparticles provided MRI negative contrast enhancement, as well as halting and even reversing tumor growth during the 76-day study duration, and without significant systemic toxicity. The lifespan of the mice treated with these targeted dual-function nanoparticles was significantly increased (Chi-square = 22.514, P < 0.0001).


CONCLUSIONS
This dual-function nanomedical platform may be a promising candidate for tumor imaging and targeted delivery of chemotherapeutic agents in vivo.
Department of Urology, The Third Affiliated Hospital, Sun Yat-Sen University, Tianhe Road 600, Guangzhou, 510630, China. xin.gao.zsu@gmail.com
Xin
X
Gao
Yun
Y
Luo
Yuanyuan
Y
Wang
Jun
J
Pang
Chengde
C
Liao
Hanlun
H
Lu
Youqiang
Y
Fang
D000704:Analysis of Variance; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000276:immunology; D019344:Lactic Acid / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000378:metabolism; D019047:Phantoms, Imaging; D011073:Polyamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D043823:Taxoids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D003287:Contrast Media; D004337:Drug Carriers; D058851:GPI-Linked Proteins; D018796:Immunoconjugates; D058185:Magnetite Nanoparticles; D009363:Neoplasm Proteins; C110843:PSCA protein, human; D011073:Polyamines; D043823:Taxoids; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; C063994:polyallylamine; D019344:Lactic Acid; D011092:Polyethylene Glycols