Styrene maleic acid polymer-encapsulated chlorophyll as a stable micellar nanoprobe for advanced anticancer photodynamic therapy

Waliul Islam, Hiroyasu Tsutsuki, Azizur Rahman, Ayaka Harada, Tianli Zhang, Katsuhiko Ono, Rayhanul Islam, Foysal Hossen, Takuro Niidome, Tomohiro Sawa*, Jun Fang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)10289–10302
Number of pages14
JournalACS Applied Polymer Materials
Issue number12
Early online date21 Nov 2023
Publication statusPublished - 08 Dec 2023
Externally publishedYes


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