Continuous Spatiotemporal Therapy of A Full-API Nanodrug via Multi-Step Tandem Endogenous Biosynthesis

Fang Fang, Sa Wang, Yueyue Song, Meng Sun, Wen-Cheng Chen, Dongxu Zhao and Jinfeng Zhang ()
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Fang Fang: Beijing Institute of Technology
Sa Wang: Beijing Institute of Technology
Yueyue Song: Beijing Institute of Technology
Meng Sun: Beijing Institute of Technology
Wen-Cheng Chen: Guangdong University of Technology
Dongxu Zhao: Beijing Institute of Technology
Jinfeng Zhang: Beijing Institute of Technology

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract 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 Fe3+, 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), Fe2+, biliverdin (BV), and bilirubin (BR) are individually biosynthesized through the PpIX-heme-CO/Fe2+/BV-BR metabolic pathway, further cooperating with released Fe3+ 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.

Date: 2023
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DOI: 10.1038/s41467-023-37315-0

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