Folic acid conjugated polymeric drug delivery vehicle for targeted cancer detection in hepatocellular carcinoma

Abstract

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 culturebased 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. K E Y W O R D S drug delivery vehicle, folic acid/folate, intra-arterial/intra-venous delivery, poly (ethylene glycol) (PEG), targeted drug delivery, transarterial chemoembolization (TACE)

Polyamidoamine Dendrimers Decorated Multifunctional Polydopamine Nanoparticles for Targeted Chemo- and Photothermal Therapy of Liver Cancer Model

“…These data suggest that PDA@DG3@PEG@FA NPs could deliver drug with enhanced efficiency due to the active targeting of folate receptors (FR) on cell membranes. The FR is a recognized biomarker for cancer cells due to its overexpression on multiple tumors including liver cancer [ 49 ]. To evaluate cellular uptake of the particles confocal laser scanning microscopy was performed.…”

Anticancer Molecular Mechanism of Protocatechuic Acid Loaded on Folate Coated Functionalized Graphene Oxide Nanocomposite Delivery System in Human Hepatocellular Carcinoma

“…Active targeting on the cell surface receptors has been researched vigorously in cancer research, since many cancer cell types display upregulations of tumor-specific receptors [ 23 ]. One of the receptors that is overexpressed in multiple tumor cells is folate receptors (FR) (alpha subunit) [ 24 , 25 ]. The cellular uptake of FA is mediated in the mammalian cells by the folate receptor (FR) [ 26 ].…”

“…The cellular uptake of FA is mediated in the mammalian cells by the folate receptor (FR) [ 26 ]. The folic acid-coated nanomaterial showed significant cellular uptake in the HepG2 cell [ 17 , 24 , 27 ]. The PEG-conjugated GO in this study enhanced the dispersibility of nanocomposites, thus providing flexibility for the interaction of FA ligands with multiple cell surface folate receptors that leads to improved specific uptake into cells [ 24 ].…”

Tumor Microenvironment Triggered Cascade‐Activation Nanoplatform for Synergistic and Precise Treatment of Hepatocellular Carcinoma

“…[ 7 ] For example, nanodrugs modified with folic acid could be recognized by the high expressed folic acid receptor on the membrane of HCC cells. [ 8 ] Although the number of anti‐tumor nanodrug is increasing, the overall therapeutic effect is not obvious. It is mainly because tumors are not the simple aggregation of tumor cells but in a complicated tumor microenvironment (TME), which influences the infiltration and therapeutic effects of nanodrugs.…”