2. Academic Validation
  3. A pH-Responsive Drug-Delivery System Based on Apatinib-Loaded Metal-Organic Frameworks for Ferroptosis-Targeted Synergistic Anti-Tumor Therapy

A pH-Responsive Drug-Delivery System Based on Apatinib-Loaded Metal-Organic Frameworks for Ferroptosis-Targeted Synergistic Anti-Tumor Therapy

  • Int J Nanomedicine. 2024 Sep 4:19:9055-9070. doi: 10.2147/IJN.S477248.
Fengyi Yang # 1 2,  Qiaoyan Dong # 3,  Zhuo Chen # 1 2,  Benjian Gao # 1 2,  Dongning Zheng 1 2,  Rui Wang 1 2,  Shu Qin 1 2,  Fangyi Peng 1 2,  Ming Luo 1 2,  Jin Yang 1 2,  Mengmei Nie 4,  Bo Li 1 2,  Xiaoli Yang 1 2
Affiliations

Affiliations

  • 1 Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People's Republic of China.
  • 2 Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People's Republic of China.
  • 3 Luzhou Senior High School, Luzhou, 646000, People's Republic of China.
  • 4 Department of Urological Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People's Republic of China.
  • # Contributed equally.
PMID: 39246426 DOI: 10.2147/IJN.S477248
Abstract

Purpose: The efficacy of systemic therapy for hepatocellular carcinoma (HCC) is limited mainly by the complex tumor defense mechanism and the severe toxic side-effects of drugs. The efficacy of apatinib (Apa), a key liver Cancer treatment, is unsatisfactory due to inadequate targeting and is accompanied by notable side-effects. Leveraging nanomaterials to enhance its targeting represents a crucial strategy for improving the effectiveness of liver Cancer therapy.

Patients and methods: A metal polyphenol network-coated apatinib-loaded metal-organic framework-based multifunctional drug-delivery system (MIL-100@Apa@MPN) was prepared by using metal-organic frameworks (MOFs) as carriers. The nanoparticles (NPs) were subsequently characterized using techniques such as X-ray diffraction (XRD), transmission electron microscopy (TEM), zeta potential measurements, and particle size analysis. In vitro experiments were conducted to observe the drug release kinetics and cytotoxic effects of MIL-100@Apa@MPN on HepG2 cells. The in vivo anti-tumor efficacy of MIL-100@Apa@MPN was evaluated using the H22 tumor-bearing mouse model.

Results: The formulated MIL-100@Apa@MPN demonstrates remarkable thermal stability and possesses a uniform structure, with measured drug-loading (DL) and encapsulation efficiency (EE) rates of 28.33% and 85.01%, respectively. In vitro studies demonstrated that HepG2 cells efficiently uptake coumarin-6-loaded NPs, and a significant increase in cumulative drug release was observed under lower pH conditions (pH 5.0), leading to the release of approximately 73.72% of Apa. In HepG2 cells, MIL-100@Apa@MPN exhibited more significant antiproliferative activity compared to free Apa. In vivo, MIL-100@Apa@MPN significantly inhibited tumor growth, attenuated side-effects, and enhanced therapeutic effects in H22 tumor-bearing mice compared to Other groups.

Conclusion: We have successfully constructed a MOF delivery system with excellent safety, sustained-release capability, pH-targeting, and improved anti-tumor efficacy, highlighting its potential as a therapeutic approach for the treatment of HCC.

Keywords

apatinib; drug-targeting delivery; ferroptosis therapy; hepatocellular carcinoma; metal-organic frameworks nanoparticles.

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