Regulation of redox balance using a biocompatible nanoplatform enhances phototherapy efficacy and suppresses tumor metastasis

Jiang, Qunying; Pan, Min; Hu, Jiaying; Sun, Junlin; Fan, Lei; Zou, Zhiqiao; Wei, Jianshuang; Yang, Xiaoquan; Liu, Xiaoqing

doi:10.1039/d0sc04983b

Cited by 47 publications

(31 citation statements)

References 58 publications

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“…When incubating AP with GSH, the absorption peaks at 412 nm decreased with increasing AP concentration, and nearly 50 µM of GSH could be completely eliminated by 20 µg mL −1 of AP dispersion after 12 h (Additional file 1 : Figure S7). This process could be attributed to the Schiff base/Michael addition reaction between GSH and the quinone groups of PDA [ 47 , 48 ]. The optical absorbance of AP/GSH mixtures under different pH values were also recorded (Additional file 1 : Figure S8).…”

Section: Resultsmentioning

confidence: 99%

NIR-II-driven and glutathione depletion-enhanced hypoxia-irrelevant free radical nanogenerator for combined cancer therapy

et al. 2021

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Background Though the combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) appears to be very attractive in cancer treatment, hypoxia and overproduced glutathione (GSH) in the tumor microenvironment (TME) limit their efficacy for further application. Results In this work, a smart hypoxia-irrelevant free radical nanogenerator (AIPH/PDA@CuS/ZIF-8, denoted as APCZ) was synthesized in situ via coating copper sulphide (CuS)-embedded zeolitic imidazolate framework-8 (ZIF-8) on the free radical initiator 2,2′-azobis[2-(2-imidazolin-2-yl)propane]-dihydrochloride (AIPH)-loaded polydopamine (PDA). APCZ showed promising GSH-depleting ability and near-infrared (NIR)-II photothermal performance for combined cancer therapy. Once internalized by 4T1 cells, the outer ZIF-8 was rapidly degraded to trigger the release of CuS nanoparticles (NPs), which could react with local GSH and sequentially hydrogen peroxide (H2O2) to form hydroxyl radical (·OH) for CDT. More importantly, the hyperthermia generated by APCZ upon 1064 nm laser excitation not only permitted NIR-II photothermal therapy (PTT) and promoted CDT, but also triggered the decomposition of AIPH to give toxic alkyl radical (·R) for oxygen-independent PDT. Besides, the PDA together with CuS greatly decreased the GSH level and resulted in significantly enhanced PDT/CDT in both normoxic and hypoxic conditions. The tumors could be completely eradicated after 14 days of treatment due to the prominent therapeutic effects of PTT/PDT/CDT. Additionally, the feasibility of APCZ as a photoacoustic (PA) imaging contrast agent was also demonstrated. Conclusions The novel APCZ could realize the cooperative amplification effect of free radicals-based therapies by NIR-II light excitation and GSH consumption, and act as a contrast agent to improve PA imaging, holding tremendous potential for efficient diagnosis and treatment of deep-seated and hypoxic tumors. Graphic abstract

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Section: Resultsmentioning

confidence: 99%

NIR-II-driven and glutathione depletion-enhanced hypoxia-irrelevant free radical nanogenerator for combined cancer therapy

et al. 2021

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“…In addition, less nanoparticle precipitate was observed when subjected to higher levels of GSH (Figure S8). The dose-dependent manners indicated a progressive erosion of the nanoinhibitor by GSH possibly because GSH could react with the quinone group on the surface of PDA through the Schiff base reaction and Michael addition, , sequentially inducing the crizotinib release. Such a GSH stimulus induced responsive release of crizotinib, as revealed by fluorescence analysis.…”

Section: Resultsmentioning

confidence: 99%

Multiple Blockades of the HGF/Met Signaling Pathway for Metastasis Suppression Using Nanoinhibitors

Shi

Wang

et al. 2021

ACS Appl. Mater. Interfaces

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The hepatocyte growth factor (HGF)/HGF receptor (Met) signaling pathway serves as a potential target for preventing tumor metastasis yet poorly explored. Here, we developed a Met-targeted nanoinhibitor to efficiently suppress metastasis via a multiple blockading HGF/Met signaling pathway. A biocompatible nanovector comprising multiple type of inhibitors enables interrupting extracellular domain dimerization and intracellular domain phosphorylation simultaneously. Such a comprehensive blockade of signaling pathway restrains unregulated tumor cell migration, invasion, and proliferation and thus remarkably suppresses metastasis in an orthotopic breast tumor model. This method provides a safe and effective option for metastasis inhibition via modulation of the cell signaling pathway. To our best knowledge, the strategy of the multiple blockading signaling pathway has not been reported for preventing tumor metastasis.

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“…5 Such photo-based modality holds great potential for disease treatment or diagnosis due to its noninvasiveness, spatiotemporal selectivity, and negligible drug resistance. [6][7][8][9][10][11] However, the traditional "always-on" photo-agents including photosensitizers and photothermal chemicals would inevitably provoke a response or phototoxicity to normal tissues, [12][13][14][15][16][17][18] and are unable to achieve precise imaging or therapy nor advance the clinical translation of the photoagents. [19][20][21] The design of activatable photo-agents offers an innovative approach to nonspecic responses.…”

Section: Introductionmentioning

confidence: 99%

Precision photothermal therapy and photoacoustic imaging by in situ activatable thermoplasmonics

Qing

et al. 2021

Chem. Sci.

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Regulation of redox balance using a biocompatible nanoplatform enhances phototherapy efficacy and suppresses tumor metastasis

Abstract: Many cancer treatments including photodynamic therapy (PDT) utilize reactive oxygen species (ROS) to kill tumor cell. However, elevated antioxidant defense systems in cancer cells give resistance to the therapy involved...

Cited by 47 publications

References 58 publications

NIR-II-driven and glutathione depletion-enhanced hypoxia-irrelevant free radical nanogenerator for combined cancer therapy

NIR-II-driven and glutathione depletion-enhanced hypoxia-irrelevant free radical nanogenerator for combined cancer therapy

Multiple Blockades of the HGF/Met Signaling Pathway for Metastasis Suppression Using Nanoinhibitors

Precision photothermal therapy and photoacoustic imaging by in situ activatable thermoplasmonics

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