Mesoporous Organosilica-Based Hydrogen Sulfide Nanogenerator for Enhanced Tumor Chemotherapy

Xu, Jian; Zhu, Weichu; Yao, Xiuzhong; Mai, Shuting; Li, Chenzi; Zhang, Minghua; Shu, Dan; Yang, Wuli

doi:10.1021/acsanm.3c01824

Cited by 3 publications

(2 citation statements)

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“…Tetrasulfur bonds can react with GSH to result in the degradation of HMSNs and the consumption of intracellular GSH and simultaneously release H 2 S, which can induce cell apoptosis at high concentration. 60 , 61 In this study, it was proved that HMSN-E could react with GSH to generate H 2 S in vitro. Herein, a WSP-1 (H 2 S probe) was used to detect intracellular generation of H 2 S in HREC.…”

Section: Resultsmentioning

confidence: 74%

“…H 2 S is a gasotransmitter that regulates several pathophysiological processes. 60 , 61 High H 2 S concentrations can induce tumor cell death via various mechanisms, 62 , 63 suggesting that high H 2 S concentrations might exert potential toxicity on normal tissue cells. Therefore, in this study, HMSNs with different tetrasulfur bond contents were prepared and characterized.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the Ocular Safety of Hollow Mesoporous Organosilica Nanoparticles with Different Tetrasulfur Bond Content

Li,

Gao,

et al. 2024

IJN

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Background Drug therapy for eye diseases has been limited by multiple protective mechanisms of the eye, which can be improved using well-designed drug delivery systems. Mesoporous silica nanoparticles (MSNs) had been used in many studies as carriers of therapeutic agents for ocular diseases treatment. However, no studies have focused on ocular biosafety. Considering that MSNs containing tetrasulfur bonds have unique advantages and have drawn increasing attention in drug delivery systems, it is necessary to explore the ocular biosafety of tetrasulfur bonds before their widespread application as ophthalmic drug carriers. Methods In this study, hollow mesoporous silica nanoparticles (HMSNs) with different tetrasulfur bond contents were prepared and characterized. The ocular biosafety of HMSN-E was evaluated in vitro on the three selected ocular cell lines, including corneal epithelial cells, lens epithelial cells and retinal endothelial cells (HREC), and in vivo by using topical eye drops and intravitreal injections. Results In cellular experiments, HMSNs caused obvious S content-dependent cytotoxic effect. HMSNs with the highest tetrasulfur bond content (HMSN-E), showed the highest cytotoxicity among all the HMSNs, and HREC was the most vulnerable cell to HMSN-E. It was shown that HMSN-E could react with intracellular GSH to generate H 2 S and decrease intracellular GSH concentration. Treatment of HREC with HMSN-E increased intracellular ROS, decreased mitochondrial membrane potential, and induced cell cycle arrest at the G1/S checkpoint, finally caused apoptosis and necrosis of HREC. Topical eye drops of HMSN-E could cause corneal damage. The intravitreal injection of HMSN-E could induce inflammation in the vitreum and ganglion cell layers, resulting in vitreous opacities and retinal abnormalities. Conclusion The incorporation of tetrasulfur bonds into HMSN can have toxic effects on ocular tissues. Therefore, when mesoporous silica nanocarriers are designed for ophthalmic pharmaceuticals, the ocular toxicity of the tetrasulfur bonds should be considered.

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Section: Resultsmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Evaluation of the Ocular Safety of Hollow Mesoporous Organosilica Nanoparticles with Different Tetrasulfur Bond Content

Li,

Gao,

et al. 2024

IJN

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Custom‐Design of Multi‐Stimuli‐Responsive Degradable Silica Nanoparticles for Advanced Cancer‐Specific Chemotherapy

Zhang,

Zhou,

Tang

et al. 2024

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Chemotherapy is crucial in oncology for combating malignant tumors but often encounters obatacles such as severe adverse effects, drug resistance, and biocompatibility issues. The advantages of degradable silica nanoparticles in tumor diagnosis and treatment lie in their ability to target drug delivery, minimizing toxicity to normal tissues while enhancing therapeutic efficacy. Moreover, their responsiveness to both endogenous and exogenous stimuli opens up new possibilities for integrating multiple treatment modalities. This review scrutinizes the burgeoning utility of degradable silica nanoparticles in combination with chemotherapy and other treatment modalities. Commencing the elucidation of degradable silica synthesis and degradation mechanisms, emphasis is placed on the responsiveness of these materials to endogenous (e.g., pH, redox reactions, hypoxia, and enzymes) and exogenous stimuli (e.g., light and high‐intensity focused ultrasound). Moreover, this exploration delves into strategies harnessing degradable silica nanoparticles in chemotherapy alone, coupled with radiotherapy, photothermal therapy, photodynamic therapy, gas therapy, immunotherapy, starvation therapy, and chemodynamic therapy, elucidating multimodal synergies. Concluding with an assessment of advances, challenges, and constraints in oncology, despite hurdles, future investigations are anticipated to augment the role of degradable silica in cancer therapy. These insights can serve as a compass for devising more efficacious combined tumor treatment strategies.

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Evaluation of Anticancer Efficacy of D-α-Tocopheryl Polyethylene-Glycol Succinate and Soluplus® Mixed Micelles Loaded with Olaparib and Rapamycin Against Ovarian Cancer

Shin,

Choi,

Yoon

et al. 2024

IJN

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Ovarian cancer has the highest mortality rate and lowest survival rate among female reproductive system malignancies. There are treatment options of surgery and chemotherapy, but both are limited. In this study, we developed and evaluated micelles composed of D-α-tocopheryl polyethylene-glycol (PEG) 1000 succinate (TPGS) and Soluplus ® (SOL) loaded with olaparib (OLA), a poly(ADP-ribose)polymerase (PARP) inhibitor, and rapamycin (RAPA), a mammalian target of rapamycin (mTOR) inhibitor in ovarian cancer. Methods: We prepared micelles containing different molar ratios of OLA and RAPA embedded in different weight ratios of TPGS and SOL (OLA/RAPA-TPGS/SOL) were prepared and physicochemical characterized. Furthermore, we performed in vitro cytotoxicity experiments of OLA, RAPA, and OLA/RAPA-TPGS/SOL. In vivo toxicity and antitumor efficacy assays were also performed to assess the efficacy of the mixed micellar system. Results: OLA/RAPA-TPGS/SOL containing a 4:1 TPGS:SOL weight ratio and a 2:3 OLA:RAPA molar ratio showed synergistic effects and were optimized. The drug encapsulation efficiency of this formulation was >65%, and the physicochemical properties were sustained for 180 days. Moreover, the formulation had a high cell uptake rate and significantly inhibited cell migration (**p < 0.01). In the in vivo toxicity test, no toxicity was observed, with the exception of the high dose group. Furthermore, OLA/RAPA-TPGS/SOL markedly inhibited tumor spheroid and tumor growth in vivo. Conclusion: Compared to the control, OLA/RAPA-TPGS/SOL showed significant tumor inhibition. These findings lay a foundation for the use of TPGS/SOL mixed micelles loaded with OLA and RAPA in the treatment of ovarian cancer.

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Mesoporous Organosilica-Based Hydrogen Sulfide Nanogenerator for Enhanced Tumor Chemotherapy

Cited by 3 publications

References 42 publications

Evaluation of the Ocular Safety of Hollow Mesoporous Organosilica Nanoparticles with Different Tetrasulfur Bond Content

Evaluation of the Ocular Safety of Hollow Mesoporous Organosilica Nanoparticles with Different Tetrasulfur Bond Content

Custom‐Design of Multi‐Stimuli‐Responsive Degradable Silica Nanoparticles for Advanced Cancer‐Specific Chemotherapy

Evaluation of Anticancer Efficacy of D-α-Tocopheryl Polyethylene-Glycol Succinate and Soluplus® Mixed Micelles Loaded with Olaparib and Rapamycin Against Ovarian Cancer

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