Near-Infrared Fluorescent Imaging of Metastatic Ovarian Cancer Using Folate Receptor-Targeted High-Density Lipoprotein Nanocarriers

Abstract

Aim The targeting efficiency of folate receptor-α (FR-α)-targeted high-density lipoprotein nanoparticles (HDL NPs) was evaluated in a syngeneic mouse model of ovarian cancer. Materials & methods Folic acid was conjugated to the surface of fluorescent-labeled HDL NPs. In vivo tumor targeting of folic acid-HDL NPs and HDL NPs were evaluated in mice with metastatic ovarian cancer following intravenous or intraperitoneal (ip.) administration. Results & discussion Intravenous FR-α-targeted HDL resulted in high uptake of the fluorescent nanoparticle in host liver and spleen. The ip. injection of fluorescent HDL produced moderate fluorescence throughout the abdomen. Conversely, animals receiving the ip. FR-α-targeted HDL showed a high fluorescence signal in ovarian tumors, surpassing that seen in all of the host tissues. Conclusion The authors' findings demonstrate that the combination of local–regional ip. administration and FR-α-directed nanoparticles provides an enhanced approach to selectively targeting ovarian cancer cells for drug treatment.

High-Density Lipoproteins: Nature’s Multifunctional Nanoparticles

“…In addition to utilizing HDL’s intrinsic interaction with SR-BI for tumor imaging, different targeting ligands, such as RGD, folate, and EGF have been attached to HDL, 148 thus potentially expanding the spectrum of cancer types that can be targeted by HDL-based strategies while reducing the off-target effects on non-cancerous cells.…”

Multimodal Magnetic Resonance and Near-Infrared-Fluorescent Imaging of Intraperitoneal Ovarian Cancer Using a Dual-Mode-Dual-Gadolinium Liposomal Contrast Agent

“…Encapsulation can also increase in vivo stability, and signal intensity21. A few mouse studies support the concept of fluorescent imaging of peritoneal ovarian tumor303132333435. These do not include an MR component and are generally targeted to one biomarker, limiting their utility to subsets of ovarian tumors.…”

Lipoproteins and lipoprotein mimetics for imaging and drug delivery

“…However, it has also been shown that HDL can be redirected from its natural targets to alternative targets. [42, 90, 122] Chen et al conjugated the arginine-glycine-aspartic acid (RGD) peptide to apoA-I on HDL labeled with gadolinium and the NIR fluorophore DiR. In vitro experiments with activated endothelial cells and macrophages, showed that the nanoparticles had been successfully re-routed to the α v β 3 -integrin (the target for RGD), since the nanoparticles bound preferentially to the endothelial cells, which overexpress the α v β 3 -integrin.…”

“…[123] Folate has been used to re-route HDL to ovarian cancer (where the folate receptor is overexpressed), as demonstrated by fluorescence imaging. [122] Interestingly, the authors found that the most successful route of administration was via intraperitoneal injection rather than intravenous injection. Another study, using iron oxide core HDL, also showed that intraperitoneal injection was viable to perform imaging with HDL-based agents.…”

“…As mentioned above, HDL has been modified by covalently adding folate and other targeting ligands to the lysine residues in apoA-I. [42, 90, 122, 171] One can imagine that similar preferential targeting to folate receptor-alpha positive malignant cells would be seen in anti-cancer drug loaded folate-containing HDLs.…”