RGD-modified ZIF-8 nanoparticles as a drug carrier for MR imaging and targeted drug delivery in myocardial infarction

Abstract

Aim: A multifunctional nanoplatform has been developed to enhance the targeting capability and biosafety of drug/siRNA for better diagnosis and treatment of myocardial infarction (MI). Materials & methods: The nanoplatform's chemical properties, biodistribution, cardiac magnetic resonance imaging (MRI) capabilities, therapeutic effects and biocompatibility were investigated. Results: The nanoplatform exhibited MI-targeting properties and pH-sensitivity, allowing for effective cardiac MRI and delivery of drugs to the infarcted myocardium. The GCD/Qt@ZIF-RGD demonstrated potential as a reliable MRI probe for MI diagnosis. Moreover, the GCD/si-SHP1/Qt@ZIF-RGD effectively suppressed SHP-1 expression, increased pro-angiogenesis gene expression and reduced cell apoptosis in HUVECs exposed to hypoxia/reoxygenation. Conclusion: Our newly developed multifunctional drug delivery system shows promise as a nanoplatform for both the diagnosis and treatment of MI.

GRAPHICAL ABSTRACT

Article highlights

• The BSA-RGD-modified ZIF-8 nanoplatform is constructed.

• The nanoplatform encapsulates quercetin and SHP-1 siRNA as the therapeutic agents, and GCD as the MRI contrast agent.

• The nanoplatform is infarct-targeting and pH-sensitive, resulting in efficient drug/siRNA delivery.

• The GCD/si-SHP1/Qt@ZIF-RGD nanoparticles produce efficient gene silencing of SHP-1 in vitro and in vivo.

• The GCD/si-Con/Qt@ZIF-RGD promote angiogenesis and alleviate cell apoptosis on HUVECs under H/R.

• The GCD/si-SHP1/Qt@ZIF-RGD display better performance on promoting angiogenesis and alleviating cell apoptosis on HUVECs under H/R.

• The GCD/Qt@ZIF-RGD can serve as a promising MRI probe for MI imaging.

• The GCD/si-SHP1/Qt@ZIF-RGD nanoparticles show good biocompatibility.

Keywords: :

• carbon dots
• myocardial infarction
• quercetin
• siRNA
• ZIF-8

Author contributions

Y Li: writing – original draft, investigation, formal analysis. M Tuerhan: writing – original draft, investigation. B Li: investigation. S Chen: investigation. Y Wang: funding acquisition. Y Zheng: writing – review & editing, supervision, investigation, funding acquisition, conceptualization.

Financial disclosure

This work was supported by the Scientific Research Common Program of Beijing Municipal Commission of Education (KM202010025028), Capital Medical Innovation Project (CX23YZ06) and Beijing Municipal Colleges and Universities High Level Talents Introduction and Cultivate Project-Beijing Great Wall Scholar Program (CIT&TCD 20180332). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All the animal studies were approved by the Capital Medical University Animal Care and Use Committee (AEEI-2020-116) and complied with the “Guide for the Care and Use of Laboratory Animals” adopted by the National Institutes of Health's Guidance.

Additional information

Funding

This work was supported by the Scientific Research Common Program of Beijing Municipal Commission of Education (KM202010025028), Capital Medical Innovation Project (CX23YZ06) and Beijing Municipal Colleges and Universities High Level Talents Introduction and Cultivate Project-Beijing Great Wall Scholar Program (CIT&TCD 20180332).