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 doi.orgResearchdoi.orgOpen source ↗.

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 doi.orgResearchdoi.orgOpen source ↗.

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 doi.orgResearchdoi.orgOpen source ↗.

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 ↗.