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A multi-responsive nano-hybrid to enhance lysosomal delivery of oxygen and photosensitizer.

Photodynamic therapy (PDT) is a promising cancer ablation method, but its efficiency is easily affected by several factors, such as the insufficient delivery of photosensitizers, low oxygen levels as well as long distance between singlet oxygen and intended organelles. A multifunctional nano-hybrid, MGAB, consisting of gelatin coated manganese dioxide and albumin-coated gold nanoclusters, was designed to overcome these issues by improving chlorin e6 (Ce6) delivery and stimulating oxygen production in the lysosome. MGAB were quickly degraded in a high hydrogen peroxide, high protease activity and low pH microenvironment, which is closely associated with tumor growth. The Ce6-loaded MGAB were picked up by tumor cells through endocytosis, degraded within the lysosome, and released oxygen and photosensitizers. Upon light irradiation, the close proximity of oxygen with photosensitizer within lysosome enabled the production of cytotoxic singlet oxygen, resulting in more effective PDT.