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Using a luciferase\/<jats:sc>d<\/jats:sc>\u2010luciferin bioluminescence system to artificially create internal light sources in cells instead of external light sources is an effective means of solving the above problems. However, high\u2010efficiency bioluminescence requires a higher concentration of luciferase in the cell, which poses a considerable challenge to the existing system of enzyme loading, delivery, activity and retention of drugs, and dramatically increases the cost of treatment. We loaded the substrate D\u2010luciferin, and the photosensitizer hypericin into a polyethyleneimine (PEI)\u2010modified nano\u2010calcium phosphate (CaP) to solve this problem. Subsequently, the plasmid DNA containing the luciferase gene was loaded onto it using the high\u2010density positive charge characteristic of PEI from the nanodrug (denoted DHDC). After the DHDC enters the tumor cell, it collapses and releases the plasmid DNA, which uses the intracellular protein synthesis system to continuously and massively express luciferase. Using endogenous ATP, Mg<jats:sup>2+<\/jats:sup>, and O<jats:sub>2<\/jats:sub> in cells, luciferase oxidizes <jats:sc>d<\/jats:sc>\u2010luciferin and produces luminescence. The luminescence triggers hypericin excitation to generate ROS and kill cancer cells. This study provides a new strategy for the application of bioluminescence in PDT treatment.<\/jats:p>","DOI":"10.1002\/cmdc.202000979","type":"journal-article","created":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T10:09:42Z","timestamp":1613556582000},"page":"1967-1974","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Plasmid DNA\u2010Based Bioluminescence\u2010Activated System for Photodynamic Therapy in Cancer Treatment"],"prefix":"10.1002","volume":"16","author":[{"given":"Di","family":"Fan","sequence":"first","affiliation":[{"name":"College of Chemistry and Materials Science Jiangsu Key Laboratory of Bio-functional Materials Jiangsu Collaborative Innovation Centre of Biomedical Functional Materials Key Laboratory of Applied Photochemistry Nanjing Normal University  Nanjing 210023 P. R. 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