Northwestern Polytechnical University: albumin nanoparticles raise radical yield 20.3-fold in mouse tumor tests

A team led by Prof. Lin Li at the School of Flexible Electronics, Northwestern Polytechnical University (China), developed a photosensitizer for mitochondria-targeted photodynamic therapy that keeps working at low oxygen levels. The work was published in Research; experiments were done in cells and in a subcutaneous transplantation model in nude mice doi.orgResearchdoi.orgOpen source ↗.

Molecular design: three donor/π-bridge branches

Photodynamic therapy uses photosensitizers that produce reactive oxygen species under light. Conventional type-II photosensitizers rely on oxygen to make singlet oxygen, which limits their action in hypoxic tumors. Type-I photosensitizers generate superoxide (•O2−) and hydroxyl (•OH) radicals through electron transfer and depend less on oxygen.

The authors built a series of cationic pyrido cyanines with a (D-π)n-A architecture (n = 1, 2, 3), named McL1, McL2 and McL3. More donor/π-bridge branches strengthened intramolecular charge transfer. McL3 showed broader visible-light absorption and a smaller singlet–triplet energy gap (ΔES1-T3 = 0.24 eV). Its •O2− production was 4.2 times that of McL1.

Albumin confinement: second boost

McL3 was then self-assembled with human serum albumin (HSA) into McL3@HSA nanoparticles with an average size of about 40 nm. Confinement in the HSA binding pocket narrowed ΔES1-T2 to 0.08 eV and raised •O2− generation to 20.3 times that of McL1 doi.orgResearchdoi.orgOpen source ↗.

Mechanistic studies indicate that HSA confinement modulates molecular conformation and increases intersystem crossing efficiency from 33% to 52%, which enables efficient type-I radical generation.

Cell and mouse results

In cells and in nude mice, McL3@HSA accumulated selectively in mitochondria. Under white-light irradiation it produced •O2− and •OH and caused structural damage to mitochondria. According to the authors, apoptosis and tumor growth inhibition were maintained under hypoxic conditions.

The results were obtained in cell cultures and in mice; clinical data are not reported. The authors describe the combination of multi-branched molecular design and albumin confinement as a route to mitochondria-targeted, hypoxia-tolerant photosensitizers doi.orgResearchdoi.orgOpen source ↗.