Prostate stem cell antigen-targeted nanoparticles with dual functional properties: in vivo imaging and cancer chemotherapy

Abstract

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). Conclusion: This dual-function nanomedical platform may be a promising candidate for tumor imaging and targeted delivery of chemotherapeutic agents in vivo.

Recent therapeutic applications of the theranostic principle with dendrimers in oncology

“…Mignani S, Rodrigues J, and Tomas H acknowledge the support of FCT-Fundação para a Ciência e a Tecnologia (project PEst-OE/ QUI/UI0674/2013, CQM, Portuguese Government funds), and ARDITI through the project M1420-01-0145-FEDER-000005 -Centro de Quí-mica da Madeira -CQM+ (Madeira [14][15][16][17][18][19][20], and Majoral J-P also acknowledges the funds from Centre National de la Recherche Scientifique (CNRS, France). Shi X acknowledges the support by the National Natural Science Foundation of China (21773026 and 81761148028), and (Mignani S, Majoral J-P and Shi X) by the Sino-French Caiyuanpei Programme.…”

Targeted superparamagnetic iron oxide nanoparticles for early detection of cancer: Possibilities and challenges

“…PSCA expression is associated with tumor stage and androgen-independence. As such, Gao et al 62 synthesized…”

Prostate cancer relevant antigens and enzymes for targeted drug delivery

“…Moreover, the nanoparticles reversed tumor growth in nude mice bearing prostate cancer xenografts without significant systemic toxicity. 60 In a similar approach, dual docetaxel and super paramagnetic iron oxide-loaded nanoparticles were prepared and delivered specifically to prostate cancer PC3 cells by using the single chain PSCA antibody scAb-PSCA 61 . In addition, the PSCA-targeted monoclonal antibody was linked to a copolymer complex containing super paramagnetic iron oxide.…”