Liposomal Nanoconfinement Enables Type I Photodynamic Conversion for Synergistic Cancer Photothermal-Immunotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Photochemistry

Background:

• Hypoxic tumors are challenging to treat with conventional therapies.
• Type-II photodynamic therapy (PDT) efficacy is limited in hypoxic environments.
• Existing strategies focus on blocking Type-II pathways via molecular engineering.

Purpose of the Study:

• To develop a nanoplatform for converting Type-II to Type-I PDT.
• To enhance therapeutic outcomes in hypoxic tumors.
• To investigate the role of liposomal confinement in modulating PDT pathways.

Main Methods:

• Fabrication of a multifunctional nanoplatform (RhM-R837@Lip) integrating liposomal confinement.
• Utilizing hemicyanine-based photosensitizers with donor-π-acceptor (D-π-A) structures.
• Investigating electron/hydrogen transfer pathways and radical generation (O2•−, •OH).
• Evaluating photothermal conversion efficiency and immune response stimulation.

Main Results:

• Achieved efficient conversion from Type-II to Type-I PDT by suppressing singlet oxygen and promoting other radical species.
• Demonstrated high photothermal conversion efficiency (56.1%) due to liposomal nanoconfinement.
• RhM-R837@Lip nanoplatform effectively inhibited tumor metastasis and stimulated systemic immune responses.

Conclusions:

• Liposomal nanoconfinement and D-π-A structure facilitate a radical-switching behavior favoring Type-I PDT.
• The developed nanoplatform offers a versatile strategy to overcome hypoxic tumor microenvironments.
• This approach improves PDT and photocatalytic performance, leading to enhanced tumor eradication.