The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Tumor Microenvironment ROS/pH Cascade-Responsive Supramolecular Nanoplatform with ROS Regeneration Property for Enhanced Hepatocellular Carcinoma Therapy
Abstract
The low targeted drug delivery efficiency, including poor tumor accumulation and penetration and uncontrolled drug release, leads to the failure of cancer therapy. Herein, a multifunctional supramolecular nanoplatform loading triptolide (TPL/PBAE TK @GA NPs) was fabricated via the host-guest interaction between glycyrrhetinic-acid-modified poly(ethylene glycol)-adamantanecarboxylic acid moiety and reactive oxygen species (ROS)/pH cascade-responsive copolymer poly(β-amino esters)-thioketal (TK)-β-cyclodextrin. TPL/PBAE TK @GA NPs could accumulate in hepatocellular carcinoma (HCC) tissue effectively, mediated by nanoscale advantage and GA' recognition to specific receptors. The elevated concentration of ROS in tumor microenvironment (TME) quickly breaks the TK linkages, causing the detachment of shell (cyclodextrin) CD layer. Then, the accompanying negative-to-positive charge-reversal of NPs was realized via the PBAE moiety protonation under the slightly acidic TME, significantly enhancing the NPs' cellular internalization. Remarkably, the pH-responsive endo/lysosome escape of PBAE core triggered intracellular TPL burst release, promoting the cancer cell apoptosis, autophagy, and intracellular ROS generation, leading to the self-amplification of ROS in TME. Afterward, the ROS positive-feedback loop was generated to further promote size-shrinkage and charge-reversal of NPs. Both in vitro and in vivo tests verified that TPL/PBAE TK @GA NPs produced a satisfactory anti-HCC therapy…
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In the citing paper
“the tumor inhibition rate reached ~ 84.14% for the GA-targeted cascade system versus ~ 70.88% (non-GA nanoparticle control), ~ 64.87% (free drug), and ~ 22.67% (saline).”
From Overcoming tumor microenvironment barriers: transformable and bioinspired nanomedicine strategies for deep tumor penetration (2026) · cites this paper as [98]
In the citing paper
“ROS and pH cascade-responsive supramolecular nanoparticles | H2O2 and low pH | GA-targeted host–guest assembly carrying triptolide | Size decrease from about 181 nm to about 125 nm; zeta potential switches from about − 2.8 mV to about + 15.4 mV; accelerated entry and burst release”
From Overcoming tumor microenvironment barriers: transformable and bioinspired nanomedicine strategies for deep tumor penetration (2026) · cites this paper as [98]
In the citing paper
“tumor inhibition rate: 84.14%”
From Overcoming tumor microenvironment barriers: transformable and bioinspired nanomedicine strategies for deep tumor penetration (2026) · cites this paper as [98]
In the citing paper
“Quantitatively, confocal depth profiling showed that at 100 µm depth the MIP nanocapsules retained ~ 6 × higher fluorescence than the non-imprinted control (CP), whereas CP signals dropped sharply beyond ~ 40–60 µm, indicating more durable deep-layer delivery rather than surface-only accumulation [98].”
From Overcoming tumor microenvironment barriers: transformable and bioinspired nanomedicine strategies for deep tumor penetration (2026) · cites this paper as [98]
In the citing paper
“pH- or ROS-only cascades, such as GA-targeted supramolecular nanoparticles, achieve modest size reduction and charge inversion that suffice for improved penetration and efficacy in hepatocellular carcinoma, but their activation strongly depends on the presence of intense oxidative stress and acidity [98].”
From Overcoming tumor microenvironment barriers: transformable and bioinspired nanomedicine strategies for deep tumor penetration (2026) · cites this paper as [98]
In the citing paper
“ROS/pH cascades detach β-cyclodextrin shells, shrink size (~ 181 to ~ 125 nm), and flip ζ potential (− 2.8 to + 15.4 mV), which accelerates triptolide entry and burst release at depth [98].”
From Overcoming tumor microenvironment barriers: transformable and bioinspired nanomedicine strategies for deep tumor penetration (2026) · cites this paper as [98]
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Diverse Applications of Nanomedicine
Pelaz, B., Alexiou, C., Alvarez-Puebla, R. A., Alves, F., Andrews, A. M., Ashraf, S., Balogh, L. P., Ballerini, L., Bestetti, A., Brendel, C., et al. (2017) · ACS Nano · doi:10.1021/acsnano.6b06040 · Cited by 1,350
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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
- Shi, J., Wang, Y., Wu, Y., Li, J., Fu, C., Li, Y., Xie, X., Fan, X., Hu, Y., Hu, C., & Zhang, J.
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2024-02-05
- Volume
- 16
- Issue
- 6
- Pages
- 7576-7592
- ISSN
- 1944-8244
- 1944-8252
- Cited by
- 22
- References
- 1
- Language
- en
- Licence
- Funders
- Natural Science Foundation of Sichuan Province (2023NSFSC1784, 2023NSFSC1195)
- National Health Commission of the People's Republic of China (ZYYCXTD-D-202209)
- Chengdu Medical College (CYZZD21-02)
- National Natural Science Foundation of China (81973662, 82304731)
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