Vitamin B_c-Bearing Hydrophilic Photosensitizer Conjugate for Photodynamic Cancer Theranostics

Abstract

The accurate diagnosis and proper therapy for cancer are essential to improve the success rate of cancer treatment. Here, we demonstrated that the vitamin Bc -bearing hydrophilic photosensitizer conjugate folic acid-polyethylene glycol-pheophorbideA (FA-PEG-PheoA) has been synthesized for the intracellular diagnosis and photodynamic therapy of a tumor. The synthesized vitamin Bc -bearing hydrophilic photosensitizer conjugate has been characterized for the folic acid receptor expressing the ability to target tumor cells, which is facilitated by the chemical conjugation with folic acid. The vitamin Bc -bearing hydrophilic photosensitizer conjugate internalization mechanism was identified through a competitive inhibition test with free folic acid. We optimized the laser-sensitive, cytotoxicity changeable, vitamin Bc -bearing hydrophilic photosensitizer conjugate concentration, which is non-cytotoxic under normal conditions and specifically cytotoxic toward cancer cells (maximum 69.15%) under laser irradiation conditions used for theranostic agents. The cancer therapeutic and diagnosis effects of synthesized conjugate were confirmed in MDA-MB-231 cells and MDA-MB-231-bearing mice. As a result, the vitamin Bc -bearing hydrophilic photosensitizer conjugate exhibited a highly photodynamic therapeutic effect, which enabled the selective detection of a folic acid receptor expressing cancer using optical imaging.

Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review

“…Additionally, they are biocompatible and have physical properties that are similar with living tissues [100]. In addition, hydrogels can possibly be used for applications delivery of hydrophilic PSs for PDT, including PAD-S31 (13,17-bis(1-carboxypropion)carbamoylethyl-3-ethenyl-8-ethoxyiminoethylidene-7-hydroxy-2,7,12,18-tetramethyl-porphyrin sodium), Mono- l -aspartyl chlorin, FA-PEG-PheoA, and aluminum (III) phthalocyanine chloride tetrasulfonic acid (Al-4), among others [101,102,103].…”

Tumor‐Specific Aptamer‐Conjugated Polymeric Photosensitizer for Effective Endo‐Laparoscopic Photodynamic Therapy

“…Synthesis and Characterization of PEG‐Ce6 : Ce6 was conjugated with PEG based on a previously reported procedure of the group . Bifunctional PEG 5 kDa (COOH, OH) (200 mg, 40 µmol) was dissolved in 2 mL of DCM.…”

“…To compare the cellular uptake of different targeting moieties, folic acid conjugated PEG‐Ce6 was prepared. Folic acid and purified PEG‐Ce6 were conjugated via a conventional carbodiimide method as previously reported by the group . To verify the nucleolin‐mediated cellular uptake of Aptamer‐PEG‐Ce6, all cells (1 × 10 5 cells per well in a 6‐well cell culture plate) were treated with Aptamer‐PEG‐Ce6 at various concentrations (0–10 µg mL −1 ) for 2 h at 37 °C.…”

“…In this regard, various attempts have been made to chemically conjugate different types of hydrophilic biopolymers with hydrophobic PSs to improve water dispersion. Indeed, when polymeric PSs were synthesized using biopolymers such as polyethylene glycol (PEG), pluronic, pullulan, hyaluronic acid, and hydroxypropyl cellulose, an increase in both their solubility and ROS generation rate in aqueous conditions was reported. Various targeting ligands such as proteins, peptides, Aptamers, polysaccharides, and small molecules have also been used to improve the tumor‐targeting efficacy to disease sites .…”

Two arms hydrophilic photosensitizer conjugates with vitamin B for cancer‐selective photodynamic therapy

“…The vitamin B receptor is overexpressed in a various human tumors . Our group has previously reported that folate is an effective marker for use with cancer targeted delivery carriers …”