“…For instance, tedious preparation procedures are required to load and deliver catalase, and the rapid deactivation and degradation of the enzyme is still an intractable problem. Nanozymes, by contrast, are much more stable and cost-effective, and can achieved tumor targeting delivery by rational surface modifications [21,22], while the potential toxicities such as metal poisoning strongly restrict their in vivo applications [23,24]. Moreover, it should also consider the effective PS loading to realize co-delivery, thus making the systems even more complicated.…”
Photodynamic therapy (PDT) has emerged as a promising tumor treatment method via light-triggered generation of reactive oxygen species (ROS) to kill tumor cells. However, the efficacy of PDT is usually restricted by several biological limitations, including hypoxia, excess glutathione (GSH) neutralization, as well as tumor resistance. To tackle these issues, herein we developed a new kind of DNA nanozyme to realize enhanced PDT and synergistic tumor ferroptosis. The DNA nanozyme was constructed via rolling circle amplification, which contained repeat AS1411 G quadruplex (G4) units to form multiple G4/hemin DNAzymes with catalase-mimic activity. Both hemin, an iron-containing porphyrin cofactor, and chlorine e6 (Ce6), a photosensitizer, were facilely inserted into G4 structure with high efficiency, achieving in-situ catalytic oxygenation and photodynamic ROS production. Compared to other self-oxygen-supplying tools, such DNA nanozyme is advantageous for high biological stability and compatibility. Moreover, the nanostructure could achieve tumor cells targeting internalization and intranuclear transport of Ce6 by virtue of specific nucleolin binding of AS1411. The nanozyme could catalyze the decomposition of intracellular H 2 O 2 into oxygen for hypoxia relief as evidenced by the suppression of hypoxia-inducible factor-1α (HIF-1α), and moreover, GSH depletion and cell ferroptosis were also achieved for synergistic tumor therapy. Upon intravenous injection, the nanostructure could effectively accumulate into tumor, and impose multi-modal tumor therapy with excellent biocompatibility. Therefore, by integrating the capabilities of O 2 generation and GSH depletion, such DNA nanozyme is a promising nanoplatform for tumor PDT/ferroptosis combination therapy.
“…For instance, tedious preparation procedures are required to load and deliver catalase, and the rapid deactivation and degradation of the enzyme is still an intractable problem. Nanozymes, by contrast, are much more stable and cost-effective, and can achieved tumor targeting delivery by rational surface modifications [21,22], while the potential toxicities such as metal poisoning strongly restrict their in vivo applications [23,24]. Moreover, it should also consider the effective PS loading to realize co-delivery, thus making the systems even more complicated.…”
Photodynamic therapy (PDT) has emerged as a promising tumor treatment method via light-triggered generation of reactive oxygen species (ROS) to kill tumor cells. However, the efficacy of PDT is usually restricted by several biological limitations, including hypoxia, excess glutathione (GSH) neutralization, as well as tumor resistance. To tackle these issues, herein we developed a new kind of DNA nanozyme to realize enhanced PDT and synergistic tumor ferroptosis. The DNA nanozyme was constructed via rolling circle amplification, which contained repeat AS1411 G quadruplex (G4) units to form multiple G4/hemin DNAzymes with catalase-mimic activity. Both hemin, an iron-containing porphyrin cofactor, and chlorine e6 (Ce6), a photosensitizer, were facilely inserted into G4 structure with high efficiency, achieving in-situ catalytic oxygenation and photodynamic ROS production. Compared to other self-oxygen-supplying tools, such DNA nanozyme is advantageous for high biological stability and compatibility. Moreover, the nanostructure could achieve tumor cells targeting internalization and intranuclear transport of Ce6 by virtue of specific nucleolin binding of AS1411. The nanozyme could catalyze the decomposition of intracellular H 2 O 2 into oxygen for hypoxia relief as evidenced by the suppression of hypoxia-inducible factor-1α (HIF-1α), and moreover, GSH depletion and cell ferroptosis were also achieved for synergistic tumor therapy. Upon intravenous injection, the nanostructure could effectively accumulate into tumor, and impose multi-modal tumor therapy with excellent biocompatibility. Therefore, by integrating the capabilities of O 2 generation and GSH depletion, such DNA nanozyme is a promising nanoplatform for tumor PDT/ferroptosis combination therapy.
“…[39]. During this process, endogenous H 2 O 2 is transformed into hydroxyl radicals (• OH), and there is a change in the valence state from ferrous to trivalent iron [40]. Despite iron being a key candidate for CDT of tumors, the targeting effect on occult malignant tumors, such as Oral Squamous Cell Carcinoma, is still insu cient and the impact is limited.…”
Section: M-fnm Boosted Anti-tumor Immunity In Vivomentioning
Background
The induction of pyroptosis holds great promise as a strategy for improving the tumor immune microenvironment. Previous pyroptosis inducers have faced limitations, including drug resistance, toxic side effects, and a lack of targeting capabilities. As a result, there is a growing demand for tumor therapeutic molecules that can overcome these obstacles. With this in mind, the objective of this study is to develop a multifunctional nanospheres that addresses these challenges by enabling high-precision targeting of tumor cells and effective pyroptosis induction.
Results
We prepared a mannose-modified MOF called mannose-doped Fe3O4@NH2-MIL-100, referred to as M-FNM. M-FNM has the ability to enter CAL27 cells through MR-mediated endocytosis, which results in a significant increase in intracellular ROS levels. This increase subsequently triggers endoplasmic reticulum stress (ER stress) and activates the PERK-eIF2α-ATF4-CHOP signaling pathway. CHOP then mediates the downstream cascade of Caspase-1, inducing pyroptosis. In in vivo experiments, M-FNM demonstrates excellent targeting ability and exhibits anti-tumor effects. Additionally, M-FNM reshapes the immune microenvironment by promoting the infiltration of anti-tumor immune cells, primarily T lymphocytes.
Conclusions
M-FNM significantly decreased tumor growth. This novel approach of inducing pyroptosis in tumor cells using M-FNM may offer new avenues for the development of effective immunotherapies for cancer treatment.
“…[16][17][18] However, there is no external stimulation required to initiate the Fenton reaction via CDT, 11,19,20 compared to other cancer therapeutic approaches. 21 Other than the Fenton reaction to produce reactive oxygen species (ROS), [22][23][24] iron-based materials promote ferroptosis-mediated cell death. Ferroptosis is an irondependent form of cell death, which is related to the intracellular iron concentration 25,26 and plays an important role in tumor growth suppression.…”
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