Synthetic biology-instructed transdermal microneedle patch for traceable photodynamic therapy

Gang He, Yashi Li, Muhammad Rizwan Younis, Lian-Hua Fu, Ting He, Shan Lei, Jing Lin and Peng Huang ()
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Gang He: Shenzhen University Health Science Center
Yashi Li: Shenzhen University Health Science Center
Muhammad Rizwan Younis: Shenzhen University Health Science Center
Lian-Hua Fu: Shenzhen University Health Science Center
Ting He: Shenzhen University Health Science Center
Shan Lei: Shenzhen University Health Science Center
Jing Lin: Shenzhen University Health Science Center
Peng Huang: Shenzhen University Health Science Center

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract 5-Aminolevulinic acid-based photodynamic therapy heavily depends on the biological transformation efficiency of 5-aminolevulinic acid to protoporphyrin IX, while the lack of an effective delivery system and imaging navigation are major hurdles in improving the accumulation of protoporphyrin IX and optimizing therapeutic parameters. Herein, we leverage a synthetic biology approach to construct a transdermal theranostic microneedle patch integrated with 5-aminolevulinic acid and catalase co-loaded tumor acidity-responsive copper-doped calcium phosphate nanoparticles for efficient 5-aminolevulinic acid-based photodynamic therapy by maximizing the enrichment of intratumoral protoporphyrin IX. We show that continuous oxygen generation by catalase in vivo reverses tumor hypoxia, enhances protoporphyrin IX accumulation by blocking protoporphyrin IX efflux (downregulating hypoxia-inducible factor-1α and ferrochelatase) and upregulates protoporphyrin IX biosynthesis (providing exogenous 5-aminolevulinic acid and upregulating ALA-synthetase). In vivo fluorescence/photoacoustic duplex imaging can monitor intratumoral oxygen saturation and protoporphyrin IX metabolic kinetics simultaneously. This approach thus facilitates the optimization of therapeutic parameters for different cancers to realize Ca2+/Cu2+-interferences-enhanced repeatable photodynamic therapy, making this theranostic patch promising for clinical practice.

Date: 2022
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DOI: 10.1038/s41467-022-33837-1

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