Abstract
In photodynamic therapy (PDT), chlorin e6 (Ce6), with its high phototoxic potential and strong absorption of visible light, penetrates deeply into photodamaged tissue. However, despite this fact, the direct application of Ce6 to PDT has been limited by its low water solubility and poor cancer cell localization. To ameliorate this situation, we report herein on the use of a hydrophilic nanoconjugate (DC) comprised of Ce6 and poly(amidoamine) dendrimer, which improves the water solubility and intracellular uptake of Ce6, thereby enhancing PDT efficacy. The synthesis of DC was verified by 1H nuclear magnetic resonance (NMR) analysis, and the coupling ratio of Ce6 introduced onto DC was 2.64. The prepared DC was spherical, with an average diameter of 61.7 ± 3.5 nm. In addition, the characteristic ultraviolet-visible absorption bands of DC in distilled water were similar to those of free Ce6 in dimethyl sulfoxide (DMSO), indicating that the Ce6 chromophore did not change upon conjugation. Investigation using fluorescence spectroscopy and confocal microscopy revealed a greater intracellular uptake of DC than of Ce6 alone. Moreover, DC exhibited significantly increased phototoxicity to human cervical cancer cells, mostly because of apoptotic cell death. These results imply that DC is a candidate for the clinical treatment of PDT.
Highlights
Photodynamic therapy (PDT) has emerged as an innovative therapeutic method for treating various oncological diseases, including gastrointestinal, esophagus, bladder and cervical cancer [1,2,3]
To prepare the hydrophilic photosensitizer, dendrimer nanoconjugate (DC), chlorin e6 (Ce6) was conjugated to the water-soluble PAMAM dendrimer by a simple one-step reaction of the amino and carboxyl groups using DCC (Figure 1)
The structure of DC was determined by 1H nuclear magnetic resonance (NMR) spectroscopy, and the result showed the expected characteristic peaks of DC (Figure S1)
Summary
Photodynamic therapy (PDT) has emerged as an innovative therapeutic method for treating various oncological diseases, including gastrointestinal, esophagus, bladder and cervical cancer [1,2,3]. This therapeutic modality is considered superior to traditional therapies such as surgery, radiotherapy and chemotherapy because it involves a minimally-invasive clinical procedure. PDT is expected to overcome multidrug resistance because the PDT cytotoxicity mechanism for cancer cells differs from that of traditional chemotherapy. PDT is based on the accumulation of a photosensitizer in specific target cells, followed by selective optical irradiation of an appropriate wavelength to generate a highly reactive oxygen species (ROS), such as singlet oxygen. The efficacy of PDT depends primarily on the intracellular accumulation of the photosensitizer in the target cells, in which the intracellular accumulation of the photosensitizer is affected by its chemical properties
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