SIRIUS, Ultra-Scintillating Upconversion Breast Implant for Remote Orthotopic Photodynamic Therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Current wireless photodynamic therapy (PDT) faces limitations in reaching deep-seated tumors due to insufficient light intensity and depth.
• Effective treatment of deep-seated cancers requires advanced delivery systems for therapies like PDT.

Purpose of the Study:

• To design and preclinically validate a flexible wireless upconversion nanoparticle (UCNP) implant (SIRIUS) for enhanced PDT delivery to deep tumors.
• To assess the efficacy of the SIRIUS UCNP implant in preclinical breast cancer models.

Main Methods:

• Incorporation of submicrometer core-shell-shell NaYF4 UCNPs into a flexible implant to boost upconversion efficiency and reduce light loss.
• In vitro evaluation using 5-Aminolevulinic Acid (5-ALA) based wireless PDT on MCF7 and MDA-MB-231 breast cancer cell lines.
• In vivo assessment of SIRIUS-driven PDT efficacy in regressing orthotopically inoculated breast tumors in a rodent model.

Main Results:

• SIRIUS implant demonstrated significantly enhanced upconversion efficiency and minimized light loss.
• In vitro studies showed significant reactive oxygen species (ROS) generation and apoptosis in breast cancer cells treated with SIRIUS-mediated PDT.
• In vivo experiments confirmed significant tumor regression in breast cancer models following SIRIUS-driven PDT.

Conclusions:

• The SIRIUS UCNP implant is a viable solution for wireless PDT, overcoming limitations of current deep-tissue treatment strategies.
• The implant shows significant potential for treating deep-seated breast tumors and has a clear path for clinical translation.
• A clinical prototype with dual cosmetic and therapeutic applications highlights the implant's versatility and future potential.