Oxygen-boosted biomimetic nanoplatform for synergetic phototherapy/ferroptosis activation and reversal of immune-suppressed tumor microenvironment

He, Zhijing; Zhou, He Ping; Zhang, Yu; Du, Xiyou; Liu, Shangui; Ji, Jianbo; Yang, Xiaoye; Zhai, Guangxi

doi:10.1016/j.biomaterials.2022.121832

Cited by 49 publications

(36 citation statements)

References 69 publications

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“…JC-1 probes are commonly used to stain cells to measure mitochondrial membrane potential. 5,20,37 MCF-7 cells were seeded and cultured in confocal dishes overnight and incubated with (I) PBS, (II) PHPF (200 μg/mL), and (III) PHPF+NIR (200 μg/mL). After 4 h of culture, the cells were incubated with JC-1 (1 μg/mL) for 30 min at 37 °C.…”

Section: ■ Methodsmentioning

confidence: 99%

“…As shown in Figure S16, after treatment with PHPF, the fluorescence of HMOX-1 was enhanced, indicating that hemin can increase the expression of HMOX-1. 19,20 HMOX-1 significantly upregulated by exposure to an 808 nm laser, which was attributed to the photothermal effect promoting cellular uptake of PHPF. In addition, the expression of HMOX-1 protein is related to the content of intracellular Fe 2+ .…”

Section: ■ Introductionmentioning

confidence: 99%

“…Heme oxygenase-1 (HMOX-1) is an enzyme that catalyzes the oxygen-dependent decomposition of hemin into biliverdin, Fe 2+ , and carbon monoxide (CO). Additional hemin can up-regulate HMOX-1 to release more Fe 2+ and a further Fenton reaction to produce •OH. , Notably, the absorption of 808 nm NIR light by PDA nanomotors can effectively a trigger photothermal effect and produce photothermally enhanced ROS, thereby participating in the Fenton reaction process described above. This process leads to the accumulation of LPO and finally leads to the photothermally enhanced ferroptosis effect. − …”

Section: Introductionmentioning

confidence: 99%

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Highly Penetrable Drug-Loaded Nanomotors for Photothermal-Enhanced Ferroptosis Treatment of Tumor

Zhang

Yang

et al. 2023

ACS Appl. Mater. Interfaces

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A kind of drug-loaded nanomotors with deep penetration was developed to improve the therapeutic effect of ferroptosis on tumor. The nanomotors were constructed by co-loading hemin and ferrocene (Fc) on the surface of bowl-shaped polydopamine (PDA) nanoparticles. The near-infrared response of PDA makes the nanomotor have high tumor penetration capability. In vitro experiments show that the nanomotors can exhibit good biocompatibility, high light to heat conversion efficiency, and deep tumor permeability. It is worth noting that under the catalysis of H2O2 overexpressed in the tumor microenvironment, the Fenton-like reagents hemin and Fc loaded on the nanomotors can increase the concentration of toxic •OH. Furthermore, hemin can consume glutathione in tumor cells and trigger the up-regulation of heme oxygenase-1, which can efficiently decompose hemin to Fe2+, thus producing the Fenton reaction and causing a ferroptosis effect. Notably, thanks to the photothermal effect of PDA, it can enhance the generation of reactive oxygen species and thus intervene in the Fenton reaction process, thereby enhancing the ferroptosis effect photothermally. In vivo antitumor results show that the drug-loaded nanomotors with high penetrability showed an effective antitumor therapeutic effect.

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Section: ■ Methodsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Highly Penetrable Drug-Loaded Nanomotors for Photothermal-Enhanced Ferroptosis Treatment of Tumor

Zhang

Yang

et al. 2023

ACS Appl. Mater. Interfaces

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“…In another design, mimetic MP@CH/BSA NPs were developed through the integration of PS Ce6 and hemin into BSA carrier, whose surface was decorated with a matrix metalloproteinase‐2 (MMP‐2) sensitive CD47 inhibitor peptide PEP20, concurrently achieving oxygen self‐supplied PDT, ferroptosis activation, and CD47 blockade therapy. [ 82 ] PEP20 was designed to be cleaved and released from MP@CH/BSA NPs by overexpressed MMP‐2, which relieved tumor immunosuppression by blocking CD47‐SIRP α interaction in TME. Interestingly, it was also found that PEP20 has an additional function that sensitized ferroptosis through enhancing IFN‐ γ production and impairing system Xc − , integrating CD47‐SIRP α blockade and ferroptosis therapy.…”

Section: Recent Design and Application Of Proinflammatory Rcd‐inducin...mentioning

confidence: 99%

Recent Organic Photosensitizer Designs for Evoking Proinflammatory Regulated Cell Death in Antitumor Immunotherapy

Sun

Wang

et al. 2023

Small Methods

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In the past decades, immunotherapy has achieved a series of clinical successes in the field of cancer. However, existing therapeutic options usually show a low immune response to solid tumors caused by immunosuppressive “cold” tumor microenvironment (TME). Several types of proinflammatory regulated cell death (RCD), mainly including ferroptosis and pyroptosis, have been studied recently, which can provide proinflammatory signals and immunogenicity necessary for remodeling TME and activating an antitumor immune response. A variety of chemotherapeutic drugs are proven to be effective in the proinflammatory RCD induction of tumor cells, but several adverse effects and intrinsic drug resistance usually occur in the therapeutic process, greatly hindering their further clinical application. The emerging organic photosensitizer (PS)‐based materials open new possibilities to effectively activate proinflammatory RCD through precise spatiotemporal regulation of intracellular reactive oxygen species‐associated signaling pathways, which can overcome many challenges encountered in current proinflammatory RCD‐mediated immunotherapy. In this review, the recent design strategies of PS probes are detailly summarized and their potential advantages for tumor‐specific proinflammatory RCD induction are discussed. Moreover, the representative examples in cancer immunotherapy are highlighted and future perspectives in this emerging field are proposed.

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“…Compared with Fe II , of which the catalytic activity in Fenton reaction is hampered by the insufficient acidity in tumor cells (optimal pH range 3–4), other transition metal-based nanocatalysts have been reported to possess high Fenton-like reaction rates even at neutral pH. − Thus, to obtain better ferroptosis-activating performance, it is of vital importance to develop ferroptosis inducers based on other transition metals, and other transition metals like copper (Cu), manganese (Mn), molybdenum (Mo), and iridium (Ir) have been proposed to activate ferroptotic-like cell death. To further enhance the therapeutic efficacy, strategies to combine ferroptosis and other cell death patterns have been reported. , For example, in a recent work of our group, we synergized apoptosis and ferroptosis by integrating phototherapy and ferroptosis activation, gaining reinforced anticancer performance against 4T1 cells …”

Section: Introductionmentioning

confidence: 99%

A Vanadium-Based Nanoplatform Synergizing Ferroptotic-like Therapy with Glucose Metabolism Intervention for Enhanced Cancer Cell Death and Antitumor Immunity

Zhang

et al. 2023

ACS Nano

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Ferroptosis activation has been considered a mighty weapon for cancer treatment, and growing attention is being paid to reinforcing tumor cells' sensitivity to ferroptosis. However, the existence of certain ferroptosis resistance mechanisms, especially the abnormal metabolism of tumor cells, has long been underestimated. We propose an enhanced ferroptosis-activating pattern via regulating tumor cells' glycometabolism and construct a nanoplatform named PMVL, which is composed of lonidamine (LND)-loaded tannic acid coordinated vanadium oxides with the camouflage of PD-L1 inhibiting peptide-modified tumor cell membrane. This work reveals that the mixed valence of vanadium (V IV and V V ) in PMVL triggers ferroptosis due to the self-cyclic valence alteration of V, the process of which generates • OH for lipid peroxide accumulation (V IV → V V ) and depletes glutathione (GSH) for glutathione peroxidase (GPX4) deactivation (V V → V IV ). Notably, LND strengthens ferroptosis by dual suppression of glycolysis (decreasing ATP supply) and the pentose phosphate pathway (decreasing NADPH production), causing anabatic GSH consumption. Besides, the inhibited glycolysis generates less intracellular lactic acid and alleviates the acidity of tumor microenvironment, preventing immunosuppressive M2 macrophage polarization. In vitro and in vivo data demonstrate the glycometabolism-intervention-enhanced ferroptosis and boosted immunity activation, potentially providing opportunities and possibilities for synergetic cancer therapy.

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Oxygen-boosted biomimetic nanoplatform for synergetic phototherapy/ferroptosis activation and reversal of immune-suppressed tumor microenvironment

Cited by 49 publications

References 69 publications

Highly Penetrable Drug-Loaded Nanomotors for Photothermal-Enhanced Ferroptosis Treatment of Tumor

Highly Penetrable Drug-Loaded Nanomotors for Photothermal-Enhanced Ferroptosis Treatment of Tumor

Recent Organic Photosensitizer Designs for Evoking Proinflammatory Regulated Cell Death in Antitumor Immunotherapy

A Vanadium-Based Nanoplatform Synergizing Ferroptotic-like Therapy with Glucose Metabolism Intervention for Enhanced Cancer Cell Death and Antitumor Immunity

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