pH-responsive Folate-PEG modified ZIF-8 Nanoparticles deliver fisetin to Aquaporin-3 for cervical cancer therapy

Area of Science:

• Nanomedicine
• Oncology
• Biochemistry

Background:

• Conventional cervical cancer treatments have limitations, including severe side effects and high recurrence rates.
• Fisetin (FIS), a natural flavonoid, shows potent anticancer activity but suffers from poor solubility, hindering clinical application.
• Developing effective and biocompatible drug delivery systems is crucial for improving cervical cancer therapy.

Purpose of the Study:

• To engineer a tumor-targeting nanotherapeutic for enhanced cervical cancer treatment.
• To encapsulate fisetin (FIS) into a zeolitic imidazolate framework-8 (ZIF-8) core functionalized with polyethylene glycol-folic acid (PEG-FA).
• To investigate the anticancer mechanisms and therapeutic efficacy of the developed nanotherapeutic both in vitro and in vivo.

Main Methods:

• Synthesis and characterization of PEG-FA@ZIF-8@FIS nanotherapeutic.
• In vitro evaluation of cancer cell proliferation and migration inhibition.
• In vivo assessment of tumor growth suppression and biocompatibility.
• Transcriptomic and lipidomic analyses to elucidate the underlying molecular mechanisms.

Main Results:

• The PEG-FA@ZIF-8@FIS system demonstrated effective suppression of cervical cancer cell proliferation, migration, and tumor growth.
• The nanotherapeutic exhibited excellent biocompatibility in both in vitro and in vivo models.
• Mechanism studies revealed that the nanotherapeutic downregulates aquaporin-3 (AQP3) expression, disrupting tumor lipid metabolism.

Conclusions:

• PEG-FA@ZIF-8@FIS represents a highly biocompatible and effective nanotherapeutic strategy for cervical cancer intervention.
• Targeted delivery of fisetin via ZIF-8 nanoparticles overcomes solubility issues and enhances therapeutic outcomes.
• Inhibition of AQP3 and subsequent metabolic disruption are key mechanisms underlying the observed anticancer effects.