Two-stage activated nano-truck enhanced specific aggregation and deep delivery for synergistic tumor ablation

Nanoscale
Ziliang ZhengRuiping Zhang

Abstract

Although nanomedicines have shown high performance in tumor theranostics, their anticancer activity is still limited by the drug delivery capacity, especially lack of targeting capability, poor tumor accumulation, and insufficient tumor deep-penetration. To address this challenge, a high biocompatibility nano-truck (BMP NT) with a two-stage delivery mechanism is designed and developed to achieve the precision therapeutic efficacy of cancer. In view of the enhanced permeability retention (EPR) effect, the surface cleavable layer of BMP NTs can be selectively removed by the overexpressed MMP-2 in a tumor-microenvironment to expose the hydrophobic segments for an induced "braking effect" strategy, resulting in a significant increase in tumor accumulation. Once internalized into cancer cells with the overproduced glutathione (GSH) and H2O2, the BMP NTs undergo the second-stage "unloading process" to release Mn2+ ions and ultrasmall Bi2S3@BSA nanoparticles, and the obtained Mn2+ ions can act as a Fenton-like catalyst for continuously catalyzing the endogenous H2O2 into highly toxic hydroxyl radicals (˙OH) for CDT. The GSH depletion will in turn improve the Mn2+-H2O2 reaction, further enhancing CDT efficiency. Meanwhile, the ultrasma...Continue Reading

References

May 11, 2011·Nano Letters·Colin M HesselBrian A Korgel
Jan 20, 2017·Nature·Daniel S Chen, Ira Mellman
Mar 16, 2017·ACS Nano·Beatriz PelazWolfgang J Parak
Feb 20, 2018·Journal of Controlled Release : Official Journal of the Controlled Release Society·Khaled SeidiTahereh Javaheri
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Mar 26, 2019·Advanced Materials·Lian-Hua FuPeng Huang
Jun 15, 2019·Journal of the American Chemical Society·Li-Sen LinXiaoyuan Chen

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Methods Mentioned

BETA
dynamic light scattering
atomic emission spectroscopy
irradiating
transmission electron microscopy
X-ray
Confocal microscopy
Fluorescence

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