Citation: Liping Dong, Jinsong Ding, Lemei Zhu, Yujun Liu, Xiang Gao, Wenhu Zhou. Copper carbonate nanoparticles as an effective biomineralized carrier to load macromolecular drugs for multimodal therapy[J]. Chinese Chemical Letters, ;2023, 34(9): 108192. doi: 10.1016/j.cclet.2023.108192 shu

Copper carbonate nanoparticles as an effective biomineralized carrier to load macromolecular drugs for multimodal therapy

Liping Dong ^a ,
Jinsong Ding ^b ,
Lemei Zhu ^a ,
Yujun Liu ^c ,
Xiang Gao ^{c, *,} ,
Wenhu Zhou ^{a, b, d, *,}

a.
Changsha Medical University, Academician Workstation, Changsha 410219, China
b.
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China
c.
State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Beijing 100850, China
d.
Key Laboratory of Biological Nanotechnology of National Health Commission, Changsha 410000, China

gaoxiang609@163.com

zhouwenhuyaoji@163.com

Received Date: 20 October 2022
Revised Date: 1 February 2023
Accepted Date: 3 February 2023
Available Online: 5 February 2023

Figures(4)

Macromolecular drugs have attracted great interest as biotherapy to cure previously untreatable diseases. For clinical translation, biomacromolecules encounter several common druggability difficulties, such as in vivo instability and poor penetration to cross physiologic barriers, thus requiring sophisticated systems for drug delivery. Inspired by the natural biomineralization via interaction between inorganic ions and biomacromolecules, herein we rationally screened biocompatible transition metals to biomineralize with carbonate for macromolecules loading. Among the metal ions, Cu²⁺ was found to be the best candidate, and its superiority over the widely studied Ca²⁺ minerals was also demonstrated. Capitalized on this finding, copper carbonate nanoparticles were prepared via a simple mixing process to co-load glucose oxidase (GOx) and a HIF-α DNAzyme (DZ), achieving ultra-high loading capacity of 61%. Upon encapsulation into nanoparticles, enzymatic activity of both drugs was passivated to avoid potential side-effects during circulation, while the drugs could be rapidly released within 1 h in response to acidic pH to fully recover their activities. The nanoparticles could accumulate into tumor via intravenous injection, facilitate the cell membrane penetration, and release the payloads of GOx, DZ and Cu²⁺ inside cells to exert a series of anti-tumor effects. GOx caused tumor starvation by catalytic glucose consumption, and the concomitantly generated H₂O₂ byproduct boosted the Cu²⁺-mediated chemodynamic therapy (CDT). Meanwhile, the DZ silenced HIF-α expression to sensitize both starvation therapy and CDT. As a result, a synergistic tumor growth inhibition was achieved. This work provides a simple method to prepare biomineralized nanoparticles, and offers a general approach for macromolecular drugs delivery via Cu²⁺-based biomineralization.
- Metal ions,
- Biomineralization,
- Drug delivery,
- Nanomedicine,
- Tumor therapy
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