Samuel Achilefu

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTFluorescence Lifetime Measurements and Biological ImagingMikhail Y. Berezin* and Samuel Achilefu*View Author Information Department of Radiology, Washington University School of Medicine, 4525 Scott Ave, St. Louis, USA* To whom correspondence should be addressed. Tel. 314-747-0701 (M.Y.B.); 314-362-8599 (S.A.). Fax: 314-747-5191. E-mail: [email protected] (M.Y.B.); [email protected] (S.A.).Cite this: Chem. Rev. 2010, 110, 5, 2641–2684Publication Date (Web):March 31, 2010Publication History Received19 October 2009Published online31 March 2010Published inissue 12 May 2010https://pubs.acs.org/doi/10.1021/cr900343zhttps://doi.org/10.1021/cr900343zreview-articleACS PublicationsCopyright © 2010 American Chemical SocietyRequest reuse permissionsArticle Views41161Altmetric-Citations1762LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Biological imaging,Dyes and pigments,Fluorescence,Fluorescence imaging,Fluorophores Get e-Alerts

Two major challenges of current photodynamic therapy (PDT) are the limited tissue penetration of excitation light and poor tumor-selectivity of the photosensitizer (PS). To address these issues, we developed a multifunctional nanoconstruct consisting of upconversion nanoparticles (UCNPs) that transform near-infrared (NIR) light to visible light and a photosensitizer zinc(II) phthalocyanine (ZnPc). Folate-modified amphiphilic chitosan (FASOC) was coated on the surface of UCNPs to anchor the ZnPc close to the UCNPs, thereby facilitating resonance energy transfer from UCNPs to ZnPc. Confocal microscopy and NIR small animal imaging demonstrated the enhanced tumor-selectivity of the nanoconstructs to cancer cells that overexpressed folate receptor. Reactive oxygen species (ROS) generation in cancer cells under a 1-cm tissue was higher upon excitation of UCNPs with the 980 nm light than that with 660 nm irradiation. In vivo PDT treatments for deep-seated tumors demonstrated that NIR light-triggered PDT based on the nanoconstructs possessed remarkable therapeutic efficacy with tumor inhibition ratio up to 50% compared with conventional visible light-activated PDT with a noticeable reduced tumor inhibition ratio of 18%. These results indicate that the multifunctional nanoconstruct is a promising PDT agent for deep-seated tumor treatment and demonstrate a new paradigm for enhancing PDT efficacy.

RATIONALE AND OBJECTIVES: To evaluate the efficacy of a novel tumor receptor-specific small-peptide-near-infrared dye conjugate for tumor detection by optical imaging. METHODS: A novel, near-infrared dye-peptide conjugate was synthesized and evaluated for tumor-targeting efficacy in a well-characterized rat tumor model (CA20948) known to express receptors for the chosen peptide. A simple continuous-wave optical imaging system, consisting of a near-infrared laser diode, a cooled CCD camera, and an interference filter, was used in this study. RESULTS: Tumor retention of two non-tumor-specific dyes, indocyanine green and its derivatized analogue, bis-propanoic acid cyanine dye (cypate), was negligible. In contrast, the receptor-specific peptide-cypate conjugate (cytate) was retained in the CA20948 tumor, with an excellent tumor-tonormal-tissue ratio in the six rats examined. CONCLUSIONS: Optical detection of tumors with a receptor-targeted fluorescent contrast agent has been demonstrated. This result represents a new direction in cancer diagnosis and patient management.