Cy5.5-Conjugated Glycol chitosan-5β-cholanic Acid Nanoparticles

Arvind Chopra

PMID: 22593949

Abstract:

Researchers have developed and are in the process of evaluating a variety of nanoparticles (NPs) that can be structurally customized to deliver imaging agents or antineoplastic drugs for the detection and/or treatment of various cancers (1). The main advantage of using NPs to deliver an imaging probe or a therapeutic drug is that, compared to conventional delivery options, NPs can transport larger amounts of a payload, within the probe or on its surface, because they have a high surface area to volume ratio (1, 2). Although the size of the NPs determines its circulation time and the route of excretion from the body (NPs <10 nm in size are removed through the kidneys and those that are 10-200 nm are taken out of circulation by the reticuloendothelial system), the chemical composition of an NP affects its functions in vivo; for more information on NPs, see Jokerst and Gambhir (3) and Fox et al. (4). Small sized NPs that are cleared from blood circulation may pass through gaps of 2-6 nm that are present in the vascular endothelium and accumulate to some extent in healthy tissues, but they are eventually removed by the lymphatic system and returned into blood circulation. Compared to normal tissues, solid tumors show a much higher uptake and prolonged retention of the NPs (known as the enhanced permeation and retention effect (EPR); for details, see Reddy (5)) because the vasculature in these lesions is leaky due to the presence of large pores (up to 1 μm) (4). In addition, reduced blood flow through the neoplastic lesion and an impaired lymphatic system leads to very little removal of NPs accumulated in the tumor (4). However, in vivo studies have shown that some types of NPs may not have optimal biodistribution in the body and tend to accumulate in tumors because of their surface chemistry, charge, size, etc.
NPs made of glycol chitosan-5β-cholanic acid, a water-soluble, biocompatible, biodegradable, and self-aggregating carbohydrate polymer (CNPs), have been shown in different models to have good potential to target therapeutic drugs to tumors (6). Factors considered important for the use of NPs to carry and deliver imaging agents or drugs to tumors are stability (for extended circulation), deformability (to avoid unwanted penetration and accumulation in angiogenic blood vessels), and the ability to be taken up rapidly by tumor cells (6). For the CNPs, these parameters have been studied primarily in vitro, and no studies have been performed to investigate these characteristic of the particles under in vivo conditions (6). The CNPs were labeled with Cy5.5, a near-infrared (NIRF) dye, and the labeled NPs (Cy5.5-CNPs) were investigated for their stability, deformability, and rapid uptake in tumor cells and in mice bearing neoplastic lesions on the flank (established with human squamous cell carcinoma SCC7 cells), brain (established with glioblastoma U87 cells), liver (established with murine colon cancer CT26 cells), and metastatic tumors (established with RFP-B16F10 cells; mouse melanoma cells transfected with the red fluorescent protein (RFP) gene) (6).

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP546189	5β-Cholanic acid		546-18-9	Price