Biolistic Delivery of Photosensitizer-Loaded Porous Si Carriers for Localized Photodynamic Therapy

Among numerous approaches for treating cancer, clinically approved photodynamic therapy (PDT) is considered a promising non-invasive therapeutic strategy for solid tumors. While PDT has distinct advantages over conventional cancer treatments, systemic exposure to the photosensitizer and its stability are some of the limitations of clinical PDT. Herein, a therapeutic strategy for highly localized focal PDT is introduced based on direct biolistic delivery of photosensitizer-loaded carriers to cancerous tumors. Degradable porous silicon microparticles (PSiMPs) are used as efficient carriers for the photosensitizer, meso-tetrahydroxy-phenylchlorin (mTHPC), and its conjugates with gold nanoparticles (AuNP-mTHPC conjugates). The loaded PSiMP carriers are successfully bombarded using a pneumatic gene gun to breast cancer cells in vitro and into tumor xenografts in vivo, and subsequent uptake of the released photosensitizer payload is demonstrated. PDT irradiation is commenced after 24 h based on the release profile, resulting in complete cell death in vitro and substantial inhibition of tumor growth in vivo. Notably, using empty PSiMP carriers also leads to some tumor growth inhibition, ascribing to its intrinsic photosensitizing activity. Treatment with AuNP-mTHPC-loaded PSiMPs exhibits a superior therapeutic effect in comparison to bombarded mTHPC-loaded carriers and administration of free mTHPC. This biolistic delivery scheme may be advantageous for precision photodynamic therapy. Degradable porous silicon microparticles loaded with the photosensitizer meso-tetrahydroxy-phenylchlorin (mTHPC) or its conjugates with gold nanoparticles are found to enhance the efficiency of photodynamic therapy when delivered locally to the tumor site via a pneumatic gene gun system.image