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Synthetic biology-instructed transdermal microneedle patch for traceable photodynamic therapy
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Synthetic biology-instructed transdermal microneedle patch for traceable photodynamic therapy
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Journal Article
Synthetic biology-instructed transdermal microneedle patch for traceable photodynamic therapy
2022
Overview
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 Ca
2+
/Cu
2+
-interferences-enhanced repeatable photodynamic therapy, making this theranostic patch promising for clinical practice.
An effective delivery system and imaging method for 5-Aminolevulinic acid (5-ALA)-based photodynamic therapy facilitated by the conversion of 5-ALA to protoporphyrin IX (PpIX) are lacking. Here, reversing the hypoxic tumour microenvironment can increase the in vivo biosynthesis of PpIX through the regulation of PpIX-related synthetases for traceable photodynamic therapy.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
