Targeted Nanoparticles for Fluorescence Imaging of Folate Receptor Positive Tumors.

Aimee J Marko,Ballav M Borah,Paula Pera,Anurag Gupta,Kevin E Siters,Ravindra K Pandey,Meden F Isaac-Lam,Joseph R Missert

doi:10.3390/biom10121651

Aimee J Marko, Ballav M Borah + Show 6 more

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https://doi.org/10.3390/biom10121651

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Abstract

This report presents the synthesis and folate receptor target-specificity of amino-functionalized polyacrylamide nanoparticles (AFPAA NPs) for near-infrared (NIR) fluorescence imaging of cancer. For the synthesis of desired nano-constructs, the AFPAA NPs (hereafter referred to as NPs) were reacted with a NIR cyanine dye (CD) bearing carboxylic acid functionality by following our previously reported approach, and the resulting conjugate (NP-CD) on further reaction with folic acid (FA) resulted in a new nano-construct, FA-NP-CD, which demonstrated significantly higher uptake in folate receptor-positive breast cancer cells (KB+) and in folate receptor over-expressed tumors in vivo. The target-specificity of these nanoparticles was further confirmed by inhibition assay in folate receptor-positive (KB+) and -negative (HT-1080) cell lines. To show the advantages of polyacrylamide (PAA)-based NPs in folate receptor target-specificity, the CD used in preparing the FA-NP-CD construct was also reacted with folic acid alone and the synthetic conjugate (CD-FA) was also investigated for its target-specificity. Interestingly, in contrast to NPs (FA-NP-CD), the CD-FA conjugate did not show any significant in vitro or in vivo specificity toward folate receptors, showing the advantages of PAA-based nanotechnology in delivering the desired agent to tumor cells.

Highlights

Medical imaging has become extremely important in the early detection, diagnosis, and treatment of cancer [1]
Fluorescence images of Colon26 tumor-bearing BALB/c mice injected with the preparations showed that, in contrast to free cyanine dye (CD), Polyacrylamide Nanoparticles (PAA NPs)–CD accumulated significantly in the tumor by 24 h
This result indicates that PAA NPs by themselves accumulate in tumors, probably through the enhanced permeability and retention (EPR) effect generated by leaky tumor vasculature and the lack of lymphatic drainage

Summary

Introduction

Medical imaging has become extremely important in the early detection, diagnosis, and treatment of cancer [1]. After cancer has been diagnosed, imaging is often used to follow the course of treatment to monitor growth or remission [2]. Among the well-established techniques, e.g., computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), X-ray, and ultrasound (US), are very important tools that can be used in the fight against deeply seated cancer. These techniques lack real time capabilities, which could be extremely useful during surgery in differentiating malignant from normal tissue. Sevick-Muraca et al [9] and others [10] have shown the utility of indocyanine dye, a type of CD, for the diagnostic imaging of breast cancer and fluorescence-enhanced optical tomography via phantom studies

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