TY - JOUR
T1 - Styrene maleic acid polymer-encapsulated chlorophyll as a stable micellar nanoprobe for advanced anticancer photodynamic therapy
AU - Islam, Waliul
AU - Tsutsuki, Hiroyasu
AU - Rahman, Azizur
AU - Harada, Ayaka
AU - Zhang, Tianli
AU - Ono, Katsuhiko
AU - Islam, Rayhanul
AU - Hossen, Foysal
AU - Niidome, Takuro
AU - Sawa, Tomohiro
AU - Fang, Jun
PY - 2023/12/8
Y1 - 2023/12/8
N2 - Progress in conventional clinical photodynamic therapy, which commonly uses low-molecular-weight photosensitizers (PSs) for cancer treatment, has been relatively slow because of the limited tumor selectivity and adverse effects of low-molecular-weight PSs. To address this issue, we have synthesized a water-soluble micellar drug called styrene–maleic acid copolymer-encapsulated chlorophyll (SMA-Chl). The SMA-Chl micelles exhibited particle sizes of approximately 90 nm, as determined by dynamic light scattering. In aqueous solution, SMA-Chl spontaneously formed micelles that showed a single peak in gel permeation chromatography using a Sephadex G-100. Interestingly, the micelles displayed fluorescence quenching in aqueous solution and 100% serum, but the fluorescence intensity was enhanced in the presence of Tween 20, sodium dodecyl sulfate, and lecithin. This result indicated that the micelles should remain stable in circulation and be disassembled upon internalization into cells through the lipid bilayer. Notably, SMA-Chl micelles alone did not exhibit appreciable cytotoxicity; however, under light exposure, SMA-Chl generated singlet oxygen and effectively suppressed the growth of cancer cells in a dose- and light-exposure-dependent manner. When SMA-Chl was administered intravenously, SMA-Chl bound with albumin, resulting in a relatively long plasma half-life and high accumulation in the tumor because of the enhanced permeability and retention effect. In the absence of light irradiation, SMA-Chl did not show significant tumor growth suppression. However, when combined with light, SMA-Chl demonstrated an excellent antitumor effect in mouse sarcoma S180 and colon C26 solid tumor models.
AB - Progress in conventional clinical photodynamic therapy, which commonly uses low-molecular-weight photosensitizers (PSs) for cancer treatment, has been relatively slow because of the limited tumor selectivity and adverse effects of low-molecular-weight PSs. To address this issue, we have synthesized a water-soluble micellar drug called styrene–maleic acid copolymer-encapsulated chlorophyll (SMA-Chl). The SMA-Chl micelles exhibited particle sizes of approximately 90 nm, as determined by dynamic light scattering. In aqueous solution, SMA-Chl spontaneously formed micelles that showed a single peak in gel permeation chromatography using a Sephadex G-100. Interestingly, the micelles displayed fluorescence quenching in aqueous solution and 100% serum, but the fluorescence intensity was enhanced in the presence of Tween 20, sodium dodecyl sulfate, and lecithin. This result indicated that the micelles should remain stable in circulation and be disassembled upon internalization into cells through the lipid bilayer. Notably, SMA-Chl micelles alone did not exhibit appreciable cytotoxicity; however, under light exposure, SMA-Chl generated singlet oxygen and effectively suppressed the growth of cancer cells in a dose- and light-exposure-dependent manner. When SMA-Chl was administered intravenously, SMA-Chl bound with albumin, resulting in a relatively long plasma half-life and high accumulation in the tumor because of the enhanced permeability and retention effect. In the absence of light irradiation, SMA-Chl did not show significant tumor growth suppression. However, when combined with light, SMA-Chl demonstrated an excellent antitumor effect in mouse sarcoma S180 and colon C26 solid tumor models.
U2 - 10.1021/acsapm.3c02042
DO - 10.1021/acsapm.3c02042
M3 - Article
SN - 2637-6105
VL - 5
SP - 10289
EP - 10302
JO - ACS Applied Polymer Materials
JF - ACS Applied Polymer Materials
IS - 12
ER -