Related Experiment Video
Updated: Feb 4, 2026
Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
pH-responsive ZIF-8@quercetin nanoparticles induce pyroptosis for targeted gastric cancer therapy
Qian Xu1,2,3,4, Xin Jin1,5,2,3,4, Siyi Song6
1Department of General Surgery, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong Province, 250014, China.
Abstract:
Gastric cancer (GC) remains a major global health burden, with limited effective therapies and poor prognosis. Quercetin (Que), a natural flavonoid, exhibits anticancer activity but suffers from poor water solubility, limited oral bioavailability, and rapid metabolic clearance, which severely restrict its clinical translation. These pharmacokinetic limitations necessitate an efficient delivery system capable of stabilizing Que in circulation and enabling tumor-specific release. To address these limitations, a zeolitic imidazolate framework-8 (ZIF-8) was developed based on nanoparticles that encapsulate Que (ZIF-8@Que), enabling high loading efficiency and pH-responsive release. ZIF-8@Que was efficiently internalized by GC cells and localized within lysosomes, where the acidic environment accelerated drug release. This process coincided with marked reactive oxygen species (ROS) generation, leading to mitochondrial membrane depolarization, ATP depletion, and ultrastructural damage. Cellular analyses further revealed features consistent with pyroptotic cell death, including lactate dehydrogenase (LDH) release, increased staining for cleaved caspase-1 and cleaved gasdermin-D (GSDMD), and enhanced TUNEL-positive signals. Compared with free Que or empty ZIF-8, ZIF-8@Que demonstrated stronger inhibition of proliferation, migration, and invasion in vitro, while in vivo studies confirmed preferential tumor accumulation, robust tumor suppression, and minimal systemic toxicity. Collectively, these findings highlight ZIF-8@Que as a safe and effective nanoparticle that integrates drug delivery with ROS-mediated pyroptosis, offering a promising strategy to overcome the limitations of Que monotherapy and advance GC therapy.
Insights
This study developed ZIF-8 nanoparticles to deliver quercetin for gastric cancer therapy. The novel ZIF-8@Que formulation enhances drug delivery, triggers cell death, and shows promising anti-cancer effects with reduced toxicity.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Gastric cancer (GC) presents a significant global health challenge with limited treatment options.
- Quercetin (Que), a natural flavonoid, has anticancer properties but faces poor solubility and bioavailability issues, hindering its clinical use.
- Efficient drug delivery systems are crucial for overcoming quercetin's limitations in cancer therapy.
Purpose of the Study:
- To develop a nanoparticle-based delivery system for quercetin to improve its efficacy in gastric cancer treatment.
- To investigate the mechanism of action of the novel nanoparticle formulation in inducing cancer cell death.
- To evaluate the therapeutic potential and safety of the quercetin-loaded nanoparticles in preclinical models.
Main Methods:
- Zeolitic imidazolate framework-8 (ZIF-8) nanoparticles were synthesized to encapsulate quercetin (ZIF-8@Que).
- The ZIF-8@Que formulation was characterized for loading efficiency and pH-responsive release.
- In vitro studies assessed cellular uptake, reactive oxygen species (ROS) generation, pyroptosis induction, and anti-cancer effects (proliferation, migration, invasion).
- In vivo studies evaluated tumor accumulation, anti-tumor efficacy, and systemic toxicity.
Main Results:
- ZIF-8@Que nanoparticles demonstrated high quercetin loading and pH-responsive release in acidic tumor microenvironments.
- Internalization by GC cells led to lysosomal drug release, enhanced ROS production, mitochondrial dysfunction, and pyroptotic cell death.
- ZIF-8@Que significantly inhibited GC cell proliferation, migration, and invasion in vitro.
- In vivo studies showed preferential tumor accumulation, robust tumor suppression, and minimal systemic toxicity compared to free quercetin.
Conclusions:
- ZIF-8@Que nanoparticles represent a promising strategy for enhancing quercetin's therapeutic efficacy against gastric cancer.
- The formulation effectively overcomes quercetin's pharmacokinetic limitations and induces cancer cell death via ROS-mediated pyroptosis.
- This nanoparticle system offers a safe and effective approach for advancing gastric cancer therapy.
More Related Videos
10:28Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
09:01Magnetic-, Acoustic-, and Optical-Triple-Responsive Microbubbles for Magnetic Hyperthermia and Pothotothermal Combination Cancer Therapy
Published on: May 22, 2020
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
01:22Target Cell Response to Hormones
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
01:16Gastric Motility
Peristaltic Waves and Chyme Formation
Upon food entry, the stomach initiates...
01:51Mechanisms of Retrovirus-induced Cancers
01:16Gastric Emptying