Synthesis of a novel nanobioconjugate for targeted photodynamic therapy of colon cancer enhanced with cannabidiol.

Cherie Ann Kruger,Nkune Williams Nkune,Heidi Abrahamse

doi:10.18632/oncotarget.28171

Abstract

Photodynamic therapy (PDT) is a promising primary treatment option for colorectal cancer (CRC), however CRC is accelerated by resilient CRC stem-like cells, which decrease its efficacy. In recent years, researchers have shown an emerging interest in the anticancer stem cell effects of cannabidiol (CBD). This study developed a targeted nanobioconjugate for specific ZnPcS4 photosensitizer intracellular accumulation within in vitro cultured human CRC cells (CaCo-2) for enhanced PDT primary treatment, as well as limited its secondary spread by combining this treatment with CBD. The final nanobioconjugate (FNBC) was successfully synthesized and characterized using various methods. The cytotoxicity of the FNBC and CBD were tested on CRC cells using laser irradiation at 673 nm with a fluency of 10 J/cm2. 24 h post treatment, morphological changes were assessed via microscopy, cell viability was measured using Annexin V-FITC and cellular nuclear DNA was visualized under fluorescent microscopy, following Hoechst staining. FNBC and CBD combinative treatment induced the most significant photodamage, leaving a staggering 6%*** viable cells. Overall, through active targeting of CRC cells using the FNBC, the enhanced PDT primary treatment of CRC was achieved, and the combinative treatment with CBD noted significant limitations on its secondary spread.

Highlights

Colorectal cancer (CRC) is the third most lethal cancer in the world, which originates from inmost linings of the colon or the rectum following genetic and epigenetic alterations of colonic epithelium into invasive adenocarcinoma [1]
Cells incubated with varying concentration of Zinc Phthalocyanine Tetrasulfonic Acid (ZnPcS4) alone (0.0312, 0.0625, 0.125 and 0.25 μM) showed no significant changes in cellular viability when compared to cells only control exposed to neither light nor PS (Figure 2)
The final nanobioconjugate (FNBC) consisting of ZnPcS4 PS, Gold nanoparticles (AuNPs)-PEGSH-NH2 and Anti-GCC Ab was successfully synthesized www.oncotarget.com for the Photodynamic Therapy (PDT) treatment of in vitro cultured CaCo-2 CRC cells

Summary

Introduction

Colorectal cancer (CRC) is the third most lethal cancer in the world, which originates from inmost linings of the colon or the rectum following genetic and epigenetic alterations of colonic epithelium into invasive adenocarcinoma [1]. It is a challenging disease to treat due to the high incidence of metastasis, drug resistance, as well as adverse side effects caused by conventional treatments such as surgical excision, chemotherapy, radiation therapy and immunotherapy [2]. The activation of photosensitizers (PSs) using a suitable wavelength of light, yields cytotoxic reactive oxygen species (ROS) and singlet oxygen, which in turn induce tumour cell death [5]. PDT is comparatively better than conventional treatments, as PSs have high affinity cancer tissues and so exert negligible effects on normal cells due to the enhanced permeability retention (EPR) phenomenon [6]. When PSs are combined with NPs, their passive uptake in tumour cells is improved via the EPR effective, which is mediated by the leaky tumour vasculature and poor lymphatic drainage of tumour tissues [7,8,9]

Methods

Results

Conclusion