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Peer-reviewedCC BY 4.0Nanomaterials

Solubilizer-Assisted Formulation of Porphyrin-Containing Lipid Nanoparticles for Photodynamic Applications

  • Yumi Kimura1
  • Rina Naganawa1
  • Yuta Takano2
  • Masatoshi Maeki3
  • Manabu Tokeshi3
  • Yusuke Sato1
  • Yuma Yamada1
  1. 1Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo 060-0812, Japan
  2. 2Research Institute for Electronic Science, Hokkaido University, Kita 20 Nishi 10, Kita-ku, Sapporo 001-0020, Japan
  3. 3Division of Applied Chemistry, Faculty of Engineering, Hokkaido University, Kita 13 Nishi 8, Kita-ku, Sapporo 060-8628, Japan
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Abstract

Hydrophobic porphyrin photosensitizers can lose photodynamic activity when densely loaded into nanoparticles because intermolecular aggregation promotes excited-state quenching. We investigated whether CAOM, a cinnamic-acid-derived oily solubilizer, could regulate the intraparticle organization of the π-extended porphyrin photosensitizer rTPA in MITO-Porter nanoparticles. Low-loading MITO-Porter (Low-MP), high-loading MITO-Porter (High-MP), and CAOM-containing High-MP (High-MP+CAOM) were prepared using the iLiNP microfluidic device. At an equivalent rTPA concentration, High-MP generated substantially less singlet oxygen than Low-MP, whereas High-MP+CAOM showed singlet oxygen generation comparable to Low-MP. High-MP+CAOM was internalized by HeLa cells and was observed in proximity to mitochondria. At comparable total lipid concentrations calculated from formulation inputs, High-MP+CAOM produced the greatest light-dependent reduction in cell viability, while dark toxicity remained limited under the tested conditions. Fluorescence spectroscopy was consistent with attenuated aggregation-caused quenching (ACQ), while cryo-transmission electron microscopy showed a more homogeneous intraparticle morphology after CAOM incorporation. These findings suggest that CAOM incorporation may support the photodynamic performance of porphyrin-containing lipid formulations under the tested conditions.

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Cite

BibTeXRIS
BibTeX
@article{kimura2026solubilizerassisted,
  title = {{Solubilizer-Assisted Formulation of Porphyrin-Containing Lipid Nanoparticles for Photodynamic Applications}},
  author = {Yumi Kimura and Rina Naganawa and Yuta Takano and Masatoshi Maeki and Manabu Tokeshi and Yusuke Sato and Yuma Yamada},
  journal = {Nanomaterials},
  year = {2026},
  month = oct,
  doi = {10.3390/nano16201329},
  url = {https://www.mdpi.com/2079-4991/16/20/1329},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Solubilizer-Assisted Formulation of Porphyrin-Containing Lipid Nanoparticles for Photodynamic Applications
AU  - Yumi Kimura
AU  - Rina Naganawa
AU  - Yuta Takano
AU  - Masatoshi Maeki
AU  - Manabu Tokeshi
AU  - Yusuke Sato
AU  - Yuma Yamada
PY  - 2026
DA  - 2026/10/01
JO  - Nanomaterials
DO  - 10.3390/nano16201329
UR  - https://www.mdpi.com/2079-4991/16/20/1329
AB  - Hydrophobic porphyrin photosensitizers can lose photodynamic activity when densely loaded into nanoparticles because intermolecular aggregation promotes excited-state quenching. We investigated whether CAOM, a cinnamic-acid-derived oily solubilizer, could regulate the intraparticle organization of the π-extended porphyrin photosensitizer rTPA in MITO-Porter nanoparticles. Low-loading MITO-Porter (Low-MP), high-loading MITO-Porter (High-MP), and CAOM-containing High-MP (High-MP+CAOM) were prepared using the iLiNP microfluidic device. At an equivalent rTPA concentration, High-MP generated substantially less singlet oxygen than Low-MP, whereas High-MP+CAOM showed singlet oxygen generation comparable to Low-MP. High-MP+CAOM was internalized by HeLa cells and was observed in proximity to mitochondria. At comparable total lipid concentrations calculated from formulation inputs, High-MP+CAOM produced the greatest light-dependent reduction in cell viability, while dark toxicity remained limited under the tested conditions. Fluorescence spectroscopy was consistent with attenuated aggregation-caused quenching (ACQ), while cryo-transmission electron microscopy showed a more homogeneous intraparticle morphology after CAOM incorporation. These findings suggest that CAOM incorporation may support the photodynamic performance of porphyrin-containing lipid formulations under the tested conditions.
SN  - 2079-4991
ER  -