Hyaluronic acid-mediated multifunctional iron oxide-based MRI nanoprobes for dynamic monitoring of pancreatic cancer

Abstract

Regarded as the most promising technology for an early and precise detection of pancreatic cancer, a sensitive nanoprobe has been developed to enhance the accumulation of contrast agent at the tumor site. Hyaluronic acid (HA)-mediated multifunctional Fe 3 O 4 nanoparticles (NPs) were used to target pancreatic cancer cells because on their cytomembrane they overexpress CD44, a receptor protein that has a high affinity to HA. The formation of HA-mediated multifunctional Fe 3 O 4 nanoparticles began with the synthesis of polyethyleneimine (PEI$NH 2 ) stabled Fe 3 O 4 NPs by slight reduction. Subsequently, the formed Fe 3 O 4 @PEI$NH 2 NPs were modified with fluorescein isothiocyanate (FITC), polyethylene glycol (mPEG-COOH) and HA in succession to form the multifunctional Fe 3 O 4 NPs denoted as HA-Fe 3 O 4 NPs.HA served as a targeting molecule to identify the surface antibody of CD44. As nanoparticles with a diameter of ca. 11.9 nm, the HA-Fe 3 O 4 NPs exhibited very high r 2 relaxivity of 321.4 mM À1 s À1 and this has proved that HA-Fe 3 O 4 NPs could be efficient T 2 -weighted magnetic resonance imaging (MRI) contrast agents. In a CCK8 cell proliferation assay of HA-Fe 3 O 4 NPs, there was no toxic response for Fe concentrations up to 100 mg mL À1 . Flow cytometry, confocal microscopy observation, and cell MRI results show that the HA-targeted groups had significantly higher cellular uptake than the nontargeted groups. This demonstrates that the HA-Fe 3 O 4 NPs are uptaken by pancreatic cells via an HAmediated targeting pathway. The HA-mediated active targeting strategy could be applied to other biomedical projects.

Hyaluronic Acid–Stabilized Fe3O4 Nanoparticles for Promoting In Vivo Magnetic Resonance Imaging of Tumors

“…The resulting nanoparticles possess positively charged surface chemistries, which were subsequently stabilized via HA through electrostatic interactions (Figure 1). Some literature reports have shown the modification of HA onto the surface of Fe 3 O 4 nanoparticles by chemical conjugation (Li et al, 2014;Gong et al, 2019;Luo et al, 2019;Zhang et al, 2020). However, this method requires tedious chemical reactions, which could result in low yield, low functionalization density due to inefficient reaction, and batch-to-batch variations in modification density.…”

Hyaluronic Acid Derivatives for Targeted Cancer Therapy

“…CD44 is a cell surface protein that plays a significant role in tumorigenesis, metastasis, and proliferation of cancer cells. Several studies have demonstrated that the interaction of CD44 and HA, an extracellular component, [48], adapted with permission from publishing authority].…”

“…Moreover, their tendency for aggregation in an aqueous medium is avoided by coating with active biopolymers and cancer-targeting agents. For example, HA modified and fluorescein isothiocyanate decorated iron nanoparticles may be utilized as an efficient probe for targeted MRI assisted cancer therapy, as shown in Figure 6(E) [48].…”

Advances in biomarkers and techniques for pancreatic cancer diagnosis

“…In 2015, Rosenberger et al modified the nanoparticle of a peptide with a high affinity to galectin-1, which is highly expressed in PC cells, thus making it an ideal MRI contrast agent [ 76 ]. Luo et al also reported a new type of nanocontrast agent—iron oxide NPs (IONPs), which were encapsulated in HA-Fe 3 O 4 -NPs (hyaluronic acid-mediated multifunctional Fe 3 O 4 nanoparticles) with fluorescein isothiocyanate (FITC) together to capture the NP by using the principle of selective recognition of hyaluronan by CD44 receptor [ 77 ]. In both cases, the accumulation of NP in the tumor increased the detection accuracy by MRI.…”