Nanophotosensitizers for Folate Receptor-Targeted and Redox-Sensitive Delivery of Chlorin E6 against Cancer Cells.

Min-Suk Kook,Byung-Hoon Kim,Chang-Min Lee,Young-Il Jeong

doi:10.3390/ma13122810

Min-Suk Kook, Byung-Hoon Kim + Show 2 more

Open Access

https://doi.org/10.3390/ma13122810

Copy DOI

Abstract

In this study, FA–PEG3500-ss-Ce6tri copolymer was synthesized to deliver photosensitizers via redox-sensitive and folate receptor-specific manner. Folic acid (FA) was attached to amine end of poly (ethylene glycol) (PEG3500) (FA–PEG3500 conjugates) and cystamine-conjugated chlorin e6 (Ce6) (Ce6-cystamine conjugates). FA–PEG3500 was further conjugated with Ce6-cystamine to produce FA–PEG3500-ss-Ce6 conjugates. To the remaining amine end group of Ce6-cystamine conjugates, Ce6 was attached to produce FA–PEG3500-ss-Ce6tri. Nanophotosensitizers of FA–PEG3500-ss-Ce6tri copolymer were smaller than 200 nm. Their shapes were disintegrated by treatment with GSH and then Ce6 released by GSH-dependent manner. Compared to Ce6 alone, FA–PEG3500-ss-Ce6tri copolymer nanophotosensitizers recorded higher Ce6 uptake ratio, reactive oxygen species (ROS) production and cellular cytotoxicity against KB and YD-38 cells. The in vitro and in vivo study approved that delivery of nanophotosensitizers is achieved by folate receptor-sensitive manner. These results indicated that FA–PEG3500-ss-Ce6tri copolymer nanophotosensitizers are superior candidate for treatment of oral cancer.

Highlights

The incidence rate and mortality of oral cancer has been continuously increasing worldwide in the last two decades
Chemotherapy, radiotherapy and immunotherapy are currently considered as treatments for oral cancers, high recurrence rates and metastasis to distant regions after sole or combined treatments are still problematic and resulted in low survival rates [4,5,6,7]
Excessive amount of cystamine was added to chlorin e6 (Ce6) solution to attach cystamine against three carboxylic acid of Ce6

Summary

Introduction

The incidence rate and mortality of oral cancer has been continuously increasing worldwide in the last two decades. Oral cancer patients are known to have the lowest survival rate at the five-year mark among major cancer types [1]. Chemotherapy, radiotherapy and immunotherapy are currently considered as treatments for oral cancers, high recurrence rates and metastasis to distant regions after sole or combined treatments are still problematic and resulted in low survival rates [4,5,6,7]. A novel treatment regimen for oral cancers is required to improve therapeutic efficacy with reduced side effects. PDT treatment for cancer can minimize adverse side effects because photosensitizers produce an excess amount of reactive oxygen

Methods

Results

Conclusion