Authors

M. Doshi; M. Krienke; S. Khederzadeh; H. Sanchez; A. Copik; J. Oyer;A. J. Gesquiere

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Abbreviated Journal Title

RSC Adv.

Keywords

GROWTH-FACTOR RECEPTOR; FOLATE-BINDING PROTEIN; PHOTODYNAMIC THERAPY; OVARIAN-CANCER; QUANTUM DOTS; FOLIC-ACID; CONJUGATED POLYMERS; DRUG-DELIVERY; CELL-LINES; IN-VIVO; Chemistry, Multidisciplinary

Abstract

First and second generation photosensitizers used in photodynamic therapy (PDT) have shown promising results in clinical applications, aided by recent improvements in light absorption efficiency and quantum yield of singlet oxygen formation. However, these photosensitizers still have several drawbacks that prevent PDT from being an efficient therapy, including lack of selectivity to diseased tissue, observation of dark toxicity, and hydrophobicity of the sensitizer. Conducting polymers are promising candidates as next generation sensitizers for PDT due to their large extinction coefficients ( > 10(7) L mol(-1) cm(-1)), ability to undergo intersystem crossing to the triplet state at high rates, and triplet energies that are close to that of oxygen. Targeting of conducting polymer poly[2-methoxy-5-(2-ethylhexyl-oxy)-p-phenylenevinylene] (MEH-PPV) nanoparticles to folate receptors (FR) was achieved by development of blended nanoparticles containing amphiphilic polymer polystyrene graft ethylene oxide functionalized with carboxylic acid (PS-PEG-COOH) with chemically active moieties that can be functionalized with folic acid. The resulting organic nanoparticles are buffer stable and exhibit excellent biocompatibility in the dark. The functionalized nanoparticles (FNPs) were studied in OVCAR3 (ovarian cancer cell line, FR+), MIA PaCa2 (pancreatic cell line, FR-), and A549 (lung cancer cell line, marginally FR+). Complete selectivity of the FNPs towards FR+ cell lines was found, and is attributed to the hydrophobicity and large negative zeta potential of the nanoparticles. Quantification of PDT results by MTS assays and flow cytometry show that PDT treatment was fully selective to the FR overexpressing cell line (OVCAR3). No cell mortality was observed for the other cell lines studied here within experimental error.

Journal Title

Rsc Advances

Volume

5

Issue/Number

47

Publication Date

1-1-2015

Document Type

Article

Language

English

First Page

37943

Last Page

37956

WOS Identifier

WOS:000353653200099

ISSN

2046-2069

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