Tumor microenvironment-responsive degradable silica nanoparticles: design principles and precision theranostic applications

Zhang, Junjie; Tang, Kaiyuan; Liu, Zilu; Zhang, Zhijing; Duan, Shufan; Wang, Hui; Yang, Hui; Yang, Dongliang; Fan, Wenpei

doi:10.1039/d3nh00388d

Cited by 8 publications

(3 citation statements)

References 166 publications

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“…Nonetheless, our as-prepared trypsin-responsive Arg-MSNs sensitively respond to excess trypsin in injured PACs to accelerate particle degradation and rapidly break down into silica-based carboxylates or amino derivatives. Thereafter, the interaction between the remaining silicon–oxygen bond structure and the adsorbed water molecules will be accelerated to create multiple silanol groups, which further engage in ion exchange reactions to liberate nontoxic silicic acid. , Eventually, these silicic acids would be excreted through urine, thus providing robust assurance for biosafety in vivo .…”

Section: Resultsmentioning

confidence: 99%

“…Thereafter, the interaction between the remaining silicon−oxygen bond structure and the adsorbed water molecules will be accelerated to create multiple silanol groups, which further engage in ion exchange reactions to liberate nontoxic silicic acid. 48,49 Eventually, these silicic acids would be excreted through urine, thus providing robust assurance for biosafety in vivo.…”

Section: Acsmentioning

confidence: 99%

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Biomimetic Trypsin-Responsive Structure-Bridged Mesoporous Organosilica Nanomedicine for Precise Treatment of Acute Pancreatitis

Wang,

Qian,

Wang

et al. 2024

ACS Nano

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Developing strategies to target injured pancreatic acinar cells (PACs) in conjunction with primary pathophysiology-specific pharmacological therapy presents a challenge in the management of acute pancreatitis (AP). We designed and synthesized a trypsin-cleavable organosilica precursor bridged by arginine-based amide bonds, leveraging trypsin's ability to selectively identify guanidino groups on arginine via Asp189 at the active S1 pocket and cleave the carboxy-terminal (C-terminal) amide bond via catalytic triads. The precursors were incorporated into the framework of mesoporous silica nanoparticles (MSNs) for encapsulating the membrane-permeable Ca 2+ chelator BAPTA-AM with a high loading content (∼43.9%). Mesenchymal stem cell membrane coating and surface modification with PAC-targeting ligands endow MSNs with inflammation recruitment and precise PAC-targeting abilities, resulting in the highest distribution at 3 h in the pancreas with 4.7-fold more accumulation than that of naked MSNs. The outcomes transpired as follows: After bioinspired MSNs' skeleton biodegradation by prematurely and massively activated trypsin, BAPTA-AM was on-demand released in injured PACs, thereby effectively eliminating intracellular calcium overload (reduced Ca 2+ level by 81.3%), restoring cellular redox status, blocking inflammatory cascades, and inhibiting cell necrosis by impeding the IκBα/NF-κB/TNF-α/IL-6 and CaMK-II/p-RIP3/p-MLKL/caspase-8,9 signaling pathways. In AP mice, a single dose of the formulation significantly restored pancreatic function (lipase and amylase reduced more by 60%) and improved the survival rate from 50 to 91.6%. The formulation offers a potentially effective strategy for clinical translation in AP treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Acsmentioning

confidence: 99%

Biomimetic Trypsin-Responsive Structure-Bridged Mesoporous Organosilica Nanomedicine for Precise Treatment of Acute Pancreatitis

Wang,

Qian,

Wang

et al. 2024

ACS Nano

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“…Particularly, stimuli-responsive nanoplatforms have been rapidly developed due to their significance in tumor targeting and controllable release . Tumor microenvironments exhibit various distinguishing characteristics, including low pH, enzymes, and a redox environment, which can be harnessed to design stimuli-responsive nanocarriers. , Among them, the abundance of reactive oxygen species (ROS), such as hydrogen peroxide (H 2 O 2 ), is produced as the disproportion of superoxide dismutase in mitochondria . Meanwhile the rapid proliferation of tumor cells and hypoxia in the tumor microenvironment further contribute to heightened H 2 O 2 generation.…”

Section: Introductionmentioning

confidence: 99%

Self-Augmented Reactive Oxygen Species-Responsive Nanoformulation with Efficient Curcumin Delivery for Inhibiting Triple-Negative Breast Cancer Cell Growth and Migration

Li,

Wang,

Jiang

et al. 2024

ACS Appl. Polym. Mater.

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Triple-negative breast cancer (TNBC) remains the second most-life-threatening carcinoma to women worldwide. Compared to conventional chemotherapeutic drugs, natural compounds, especially curcumin (CUR), have been proven to have therapeutical potential in TNBC treatment. To improve the accumulation of CUR at tumor sites, a reactive oxygen species (ROS)-responsive nanocarrier was developed (CUR@Bio/PE-NPs) with CUR entrapment and biotin conjugation, exhibiting a strong affinity for breast cancer cells. CUR@Bio/PE-NPs demonstrated a particle size of 142.9 nm, good stability, and an encapsulation efficiency of 63.67%, while realizing a positive feedback loop of ROS-accelerated CUR release and CUR-induced ROS generation in tumor cells. In vitro studies revealed that CUR@Bio/PE-NPs induced ROS generation effectively and promoted ∼1.30and 1.36-fold cellular uptake of Nile red@Bio/PE-NPs compared to nontargeted nanoparticles in MDA-MB-231 and 4T1 cells, respectively. In addition, CUR@Bio/PE-NPs suppressed their proliferation (IC 50 , MDA-MB-231:3.277 μg/mL, 4T1:5.259 μg/mL) with increased apoptosis and cell cycle arrest while preventing cell-migration and invasion. Importantly, in a 4T1 tumor xenografted mice model, nanoformulation prolonged curcumin accumulation at tumor sites, modulated the tumor immune microenvironment and prevented tumor growth and lung metastases without significant toxicity. In short, the in vitro and in vivo results suggested CUR@Bio/PE-NPs as a promising strategy for TNBC therapy.

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

Zhang,

Zhou,

Tang

et al. 2024

Small

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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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Tumor microenvironment-responsive degradable silica nanoparticles: design principles and precision theranostic applications

Abstract: Silica nanoparticles have emerged as promising candidates in the field of nanomedicine due to their remarkable versatility and customizable properties. However, concerns about their potential toxicity in healthy tissues and...

Cited by 8 publications

References 166 publications

Biomimetic Trypsin-Responsive Structure-Bridged Mesoporous Organosilica Nanomedicine for Precise Treatment of Acute Pancreatitis

Biomimetic Trypsin-Responsive Structure-Bridged Mesoporous Organosilica Nanomedicine for Precise Treatment of Acute Pancreatitis

Self-Augmented Reactive Oxygen Species-Responsive Nanoformulation with Efficient Curcumin Delivery for Inhibiting Triple-Negative Breast Cancer Cell Growth and Migration

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

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