Summary: It is critical to achieve efficient delivery of photosensitizers throughout the tumor sites in order to obtain therapeutically relevant photodynamic treatment (PDT) efficacy and desired clinical outcomes. However, synthesis and deposition of dense collagen in the tumor extracellular matrix (ECM) result in poor penetration and accumulation of photosensitizer within the tumor tissue. Herein, we develop a losartan pretreatment strategy to deplete tumor collagen, thereby improving the tumor accumulation and PDT efficacy of Chlorine 6 (Ce6) loaded periodic mesoporous organosilica (Ce6-PMO) photodynamic nanoplatform. After pretreatment with losartan in vivo, the tumor collagen I fraction in tumor tissue was significantly reduced by 53% and tumor uptake of Ce6-PMO subsequently administered via peritumoral and intravenous routes was remarkably enhanced. Further, combination of losartan and Ce6-PMO provided the best therapy efficacy, and the suppression rate of tumor volume was measured up to 82%. This study introduces a highly promising synergetic strategy to improve nanoplatform-based PDT efficacy for cancer therapy.
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