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Development of polymeric microbubbles targeted to prostate-specific membrane antigen as prototype of novel ultrasound contrast agents

Sanna, Vanna and Pintus, Gianfranco and Bandiera, Pasquale and Anedda, Roberto and Punzoni, Stefania and Sanna, Bastiano and Migaleddu, Vincenzo and Uzzau, Sergio and Sechi, Mario (2011) Development of polymeric microbubbles targeted to prostate-specific membrane antigen as prototype of novel ultrasound contrast agents. Molecular Pharmaceutics, Vol. 8 (3), p. 748-757. ISSN 1543-8384. eISSN 1543-8392. Article.

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DOI: 10.1021/mp100360g

Abstract

Ultrasound-targeted microbubbles (MBs) offer new opportunities to enhance the capabilities of diagnostic ultrasound (US) imaging to specific pathological tissue. Herein, we report on the design and development of a novel prototype of US contrast agent based on polymeric MBs targeted to prostate-specific membrane antigen (PSMA) for use in the diagnosis of prostate cancer (PCa). First, a set of air-filled MBs by a variety of biocompatible polymers were prepared and characterized in terms of morphology and echogenic properties after exposure to US. MBs derived from poly(d,l-lactic-co-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG) copolymer resulted as the most effective in terms of reflectivity. Such polymer was therefore preconjugated with a urea-based PSMA inhibitor molecular probe (DCL), and the obtained MBs were investigated in vitro for their targeting efficacy toward PSMA positive PCa (LNCaP) cells. Fluorescence microscopy proved a specific and efficient adhesion of targeted MBs to LNCaP cells. To our knowledge, this work reports the first model of polymeric MBs appropriately engineered to target PSMA, which might be further optimized and used for PCa diagnosis and potential carriers for selective drug delivery.

Item Type:Article
ID Code:6408
Status:Published
Refereed:Yes
Uncontrolled Keywords:Targeted microbubbles, biodegradable polymers, ultrasound, contrast agents, prostate cancer, prostate-specific membrane antigen (PSMA)
Subjects:Area 05 - Scienze biologiche > BIO/10 Biochimica
Area 06 - Scienze mediche > MED/07 Microbiologia e microbiologia clinica
Area 03 - Scienze chimiche > CHIM/08 Chimica farmaceutica
Area 05 - Scienze biologiche > BIO/16 Anatomia umana
Divisions:001 Università di Sassari > 02 Centri > Centro di eccellenza interdisc. sviluppo ricerca biotecnologica e studio biodiversità della Sardegna e dell'area mediterranea
002 Altri enti e centri di ricerca del Nord Sardegna > SMIRG-Sardinian Mediterranean Imaging Research Group, Sassari
001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
002 Altri enti e centri di ricerca del Nord Sardegna > Porto Conte Ricerche, Alghero
001 Università di Sassari > 01 Dipartimenti > Scienze del farmaco
Publisher:American Chemical Society
ISSN:1543-8384
eISSN:1543-8392
Copyright Holders:© 2011 American Chemical Society
Deposited On:25 Aug 2011 13:39

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