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Folic acid conjugated polymeric drug delivery vehicle for targeted cancer detection in hepatocellular carcinoma
Author(s) -
Koirala Nischal,
Das Dola,
Fayazzadeh Ehsan,
Sen Sanghamitra,
McClain Andrew,
Puskas Judit E.,
Drazba Judith A.,
McLennan Gordon
Publication year - 2019
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.36758
Subject(s) - folate receptor , in vivo , hepatocellular carcinoma , targeted drug delivery , liver cancer , drug delivery , fluorescein isothiocyanate , cancer research , pharmacology , peg ratio , cell culture , ethylene glycol , cancer , materials science , cancer cell , drug , medicine , chemistry , biology , nanotechnology , genetics , microbiology and biotechnology , quantum mechanics , fluorescence , physics , organic chemistry , finance , economics
Targeted therapies provide increased efficiency for the detection and treatment of cancer with reduced side effects. Folate receptor (alpha subunit) is overexpressed in multiple tumors including liver cancer. In this study, we evaluated the specificity and toxicity of a folic acid‐containing drug delivery vehicle (DDV) in a hepatocellular carcinoma (HCC) model. The DDV was prepared with two units each of folic acid (FA) and fluorescein isothiocyanate (FITC) molecules and conjugated to a central poly (ethylene glycol) (PEG) core via a modified chemo‐enzymatic synthetic process. Rat hepatoma (N1S1) and human monocytic (U937) cell lines were used for cell culture‐based assays and tested for DDV uptake and toxicity. Folate receptor expressions in liver tissues and cell lines were verified using standard immunohistochemistry techniques. Rat HCC model was used for in vivo assessment. The DDV was injected via intra‐arterial or intravenous methods and imaged with IVIS spectrum in vivo imaging system. Strong signals of FITC in the liver tumor region correlated to targeted DDV uptake. The use of PEG enhanced water‐solubility and provided flexibility for the interaction of FA ligands with multiple cell surface folate receptors that resulted in increased specific uptake. Our study suggested that PEG incorporation and folate targeting via intra‐arterial approach is an efficient strategy for targeted delivery in HCC therapy.