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NO-dependent vasodilation and deep tumor penetration for cascade-amplified antitumor performance
Abstract
Nonspecific biodistribution and poor permeability of conventional therapeutic agents in solid tumors severely compromised the antitumor efficacy. Herein, we report a cascade tumor therapeutic nanoplatform consisting of docosahexaenoic acid (DHA) and nicorandil (NI), namely DNP, to specifically produce cytotoxic agents in tumor cells as well as dilating blood vessels to increase the intratumoral oxidative stress levels. The DHA embedded in the membrane could generate reactive oxygen species (ROS) meanwhile NI produced nitric oxide (NO) in response to intracellular glutathione (GSH) in tumors. Notably, the two functional species could further react in situ to form a more tumoricidal reactive nitrogen species (RNS), causing selectively cascade amplification of antitumor performance. In addition, NO-induced vasodilation could consequently result in a series of functions, including hypoxia relief and deep tumor transportation. In general, we anticipate that the DNP could show great potential for tumor-specific treatment by selectively producing RNS precursors in response to the interior environment of tumor cells for hypoxia normalization and tumor inhibition.
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“RPC@M nanozyme | Photocatalytic water splitting lowers interstitial fluid pressure; resveratrol reduces collagen and solid stress | Tumor-bearing mice | Interstitial fluid pressure and solid stress (TIFP and TISP) | CLSM spheroid penetration; penetration depth: 80 μm | — | [52, 53]”
From Overcoming tumor microenvironment barriers: transformable and bioinspired nanomedicine strategies for deep tumor penetration (2026) · cites this paper as [52]
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Cited by
Sorted by citations
Sheng, J., Yuan, W., Zhang, M., Chen, Z., Qi, Y., Zhao, Y., & Zhang, S. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04028-7 · Cited by 35
Metadata
- Authors
- Xu, Q., Chen, G., Chen, G., Wu, H., Yang, Y., Mai, Z., Sun, R., Luan, P., Guo, C., Yu, M., Peng, Z., & Yu, Z.
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2022-07
- Volume
- 347
- Pages
- 389-399
- ISSN
- 0168-3659
- Cited by
- 35
- References
- 2
- Language
- en
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- Xu, Q., Chen, G., Chen, G., Wu, H., Yang, Y., Mai, Z., Sun, R., Luan, P., Guo, C., Yu, M., Peng, Z., & Yu, Z. (2022). NO-dependent vasodilation and deep tumor penetration for cascade-amplified antitumor performance. Journal of Controlled Release. https://doi.org/10.1016/j.jconrel.2022.05.022