Autonomous metal-organic framework nanorobots for active mitochondria-targeted cancer therapy
Abstract
Nanorobotic manipulation to access subcellular organelles remains unmet due to the challenge in achieving intracellular controlled propulsion. Intracellular organelles, such as mitochondria, are an emerging therapeutic target with selective targeting and curative efficacy. We report an autonomous nanorobot capable of active mitochondria-targeted drug delivery, prepared by facilely encapsulating mitochondriotropic doxorubicin-triphenylphosphonium (DOX-TPP) inside zeolitic imidazolate framework-67 (ZIF-67) nanoparticles. The catalytic ZIF-67 body can decompose bioavailable hydrogen peroxide overexpressed inside tumor cells to generate effective intracellular mitochondriotropic movement in the presence of TPP cation. This nanorobot-enhanced targeted drug delivery induces mitochondria-mediated apoptosis and mitochondrial dysregulation to improve the in vitro anticancer effect and suppression of cancer cell metastasis, further verified by in vivo evaluations in the subcutaneous tumor model and orthotopic breast tumor model. This nanorobot unlocks a fresh field of nanorobot operation with intracellular organelle access, thereby introducing the next generation of robotic medical devices with organelle-level resolution for precision therapy.
Additional Information
© 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). This study was supported by Shenzhen Science and Technology Innovation Commission (grant number RCJC20200714114557005). Author contributions: Conceptualization: X.P. and S.T. Methodology: X.P., D.T., D.Z., and S.T. Investigation: X.P., D.T., D.Z., Y.L., Q.C., S.T., F.W., and H.H. Visualization: X.P. and S.T. Supervision: S.T., W.G., and S.W. Writing (original draft): X.P. and S.T. Writing (review and editing): X.P., S.T., H.L., X.Z., W.G., and S.W. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. The authors declare that they have no competing interests.Attached Files
Published - sciadv.adh1736.pdf
Supplemental Material - sciadv.adh1736_movies_s1_to_s7.zip
Supplemental Material - sciadv.adh1736_sm.pdf
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Additional details
- PMCID
- PMC10256165
- Eprint ID
- 121954
- Resolver ID
- CaltechAUTHORS:20230615-129155000.9
- RCJC20200714114557005
- Shenzhen Science and Technology Innovation Commission
- Created
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2023-06-21Created from EPrint's datestamp field
- Updated
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2023-06-21Created from EPrint's last_modified field