Abstract

Hybrid liposomes (HLs) can be prepared by simply sonicating a mixture of vesicular and micellar molecules in a buffer solution. This study aimed to elucidate the therapeutic effects and ability of HLs to detect (diagnosis) cancer in an orthotopic graft mouse model of colorectal cancer with HCT116 cells for the use of HLs as theranostic agents. In the absence of a chemotherapeutic drug, HLs exhibited therapeutic effects by inhibiting the growth of HCT116 colorectal cancer cells in vitro, possibly through an increase in apoptosis. Intravenously administered HLs also caused a remarkable reduction in the relative cecum weight in an orthotopic graft mouse model of colorectal cancer. A decrease in tumor size in the cecal sections was confirmed by histological analysis using HE staining. TUNEL staining indicated an induction of apoptosis in HCT116 cells in the orthotopic graft mouse model of colorectal cancer. For the detection (diagnosis) of colorectal cancer by HLs, the accumulation of HLs encapsulating a fluorescent probe (ICG) was observed in HCT116 cells in the in vivo colorectal cancer model following intravenous administration. These data indicate that HLs can accumulate in tumor cells in the cecum of the orthotopic graft mouse model of colorectal cancer for a prolonged period of time, and inhibit the growth of HCT116 cells.

Highlights

  • The mortality rate associated with cancer is high worldwide

  • The Hybrid liposomes (HLs) appear to exert their therapeutic effect by directly inhibiting the growth of HCT116 cells, in the absence of any chemotherapeutic agent, perhaps by stimulating apoptosis in vitro

  • Intravenous HLs administration caused an induction of apoptosis in the HCT116 cells in the cecum of the orthotopic graft model mice, as assessed by TUNEL staining

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Summary

Introduction

The mortality rate associated with cancer is high worldwide. Colorectal cancer, in particular, is associated with a high mortality rate, with the number of reported deaths being over 700,000 in 2012 (Ferlay et al, 2015). Surgical resection is most commonly used for the treatment for the earlier-stage colorectal cancer. 5-Fluorouracil (5-FU) has been used as a chemotherapeutic agent for the treatment of colorectal cancer (Longley et al, 2003). FOLFOX (folinic acid, 5-FU, and oxaliplatin) is a 5FU-based combination of chemotherapeutic drugs used to treat colorectal cancer and is known to improve the survival rate of colorectal cancer patients (Andre et al, 2004; Bokemeyer et al, 2011; Taieb et al, 2017). The development of chemotherapeutic agents with minimal side-effects is desired to improve the quality of life of the patients

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