Continuous Spatiotemporal Therapy of A Full-API Nanodrug via Multi-Step Tandem Endogenous Biosynthesis.
Fang FangSa WangYueyue SongMeng SunWen-Cheng ChenDongxu ZhaoJinFeng ZhangPublished in: Nature communications (2023)
Nanomedicine holds great promise to enhance cancer therapy. However, low active pharmaceutical ingredient (API) loading content, unpredictable drug release, and potential toxicity from excipients limit their translational capability. We herein report a full-API nanodrug composed of FDA-approved 5-aminolevulinic acid (ALA), human essential element Fe 3+ , and natural bioactive compound curcumin with an ideal API content and pH-responsive release profile for continuous spatiotemporal cancer therapy achieved by multi-step tandem endogenous biosynthesis. First, ALA enzymatically converts into photosensitizer protoporphyrin IX (PpIX). Afterward, multiple downstream products including carbon monoxide (CO), Fe 2+ , biliverdin (BV), and bilirubin (BR) are individually biosynthesized through the PpIX-heme-CO/Fe 2+ /BV-BR metabolic pathway, further cooperating with released Fe 3+ and curcumin, ultimately eliciting mitochondria damage, membrane disruption, and intracytoplasmic injury. This work not only provides a paradigm for exploiting diversified metabolites for tumor suppression, but also presents a safe and efficient full-API nanodrug, facilitating the practical translation of nanodrugs.
Keyphrases
- cancer therapy
- drug delivery
- drug release
- photodynamic therapy
- metal organic framework
- oxidative stress
- lipopolysaccharide induced
- endothelial cells
- lps induced
- aqueous solution
- cell wall
- cell death
- mesenchymal stem cells
- machine learning
- deep learning
- risk assessment
- visible light
- artificial intelligence
- induced pluripotent stem cells
- silver nanoparticles
- stem cells
- drug administration