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

Fang, Fang, Wang, Sa, Song, Yueyue, Sun, Meng, Chen, Wen-Cheng, Zhao, Dongxu, Zhang, Jinfeng·2023·Nature Communications
DOI 10.1038/s41467-023-37315-0PMC PMC10039359
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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 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.

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Metadata

Authors
Fang, F., Wang, S., Song, Y., Sun, M., Chen, W.-C., Zhao, D., & Zhang, J.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-03-25
Volume
14
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-023-37315-0
PMC
PMC10039359
Cited by
112
References
1
Language
en
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