Theranostic nanoparticles based on PEGylated hyaluronic acid for the diagnosis, therapy and monitoring of colon cancer

Abstract

Colon cancer is the second leading cause of cancer-related death in the United States. The considerable mortality from colon cancer is due to metastasis to other organs, mainly the liver. In the management of colon cancer, early detection and targeted therapy are crucial. In this study, we aimed to establish a versatile theranostic system for early tumor detection and targeted tumor therapy by using poly(ethylene glycol)-conjugated hyaluronic acid nanoparticles (P-HA-NPs) which can selectively accumulate in tumor tissue. For the diagnostic application, a near-infrared fluorescence (NIRF) imaging dye (Cy 5.5) was chemically conjugated onto the HA backbone of P-HA-NPs. After intravenous injection of Cy5.5-P-HA-NPs into the tumor-bearing mice, small-sized colon tumors as well as liver-implanted colon tumors were effectively visualized using the NIRF imaging technique. For targeted therapy, we physically encapsulated the anticancer drug, irinotecan (IRT), into the hydrophobic cores of P-HA-NPs. Owing to their notable tumor targeting capability, IRT-P-HA-NPs exhibited an excellent antitumor activity while showing a reduction in undesirable systemic toxicity. Importantly, we demonstrated the theranostic application using Cy5.5-P-HA-NPs and IRT-P-HA-NPs in orthotopic colon cancer models. Following the systemic administration of Cy5.5-P-HA-NPs, neoplasia was clearly visualized, and the tumor growth was effectively suppressed by intravenous injection of IRT-P-HA-NPs. It should be emphasized that the therapeutic responses could be simultaneously monitored by Cy5.5-P-HA-NPs. Our results suggest that P-HA-NPs can be used as a versatile theranostic system for the early detection, targeted therapy, and therapeutic monitoring of colon cancer.

Doxorubicin-loaded polysaccharide nanoparticles suppress the growth of murine colorectal carcinoma and inhibit the metastasis of murine mammary carcinoma in rodent models

“…Colorectal carcinoma causes approximately 50,000 deaths in the United States and 655,000 deaths throughout the world per year [4,5]. Breast cancer is the most common malignancy in women, with one in nine women developing breast cancer during their lifetime [6] and cancer death with more than a million newly diagnosed cases annually worldwide [3].…”

Polymeric nanoparticles for colon cancer therapy: overview and perspectives

“…116 With intravenously injected nanoparticles in colon tumor bearing mouse models, P-HA-NPs clearly visualized tumors using a NIRF imaging technique as well as effectively suppressed tumor growth due to their targeting over overexpressed HA receptors. Moreover, the therapeutic response could be simultaneously monitored by Cy5.5-P-HA-NPs.…”

PEG-capped, lanthanide doped GdF3 nanoparticles: luminescent and T2 contrast agents for optical and MRI multimodal imaging

“…29 In recent experiments the PEG-capped nanoparticle cellular uptake was investigated and in numerous experiments a higher uptake on PEG coated nanoparticles was demonstrated due to the higher affinity of tumor cells for this coating material. 30,31 For these reasons, we found it interesting to investigate the possibility of preparing PEG-capped, water dispersible GdF 3 based NPs, as bimodal probes for both optical and MRI contrast agents. In this work, we study the luminescence and contrast agent properties of PEG-capped Tm 3+ /Yb 3+ or Er 3+ /Yb 3+ GdF 3 NPs, prepared by a facile, environmentally friendly, one-pot hydrothermal synthesis, using water as a solvent.…”