The Synergistic Anticancer Effect of Dual Drug- (CisplatinEpigallocatechin Gallate)‎ Loaded Gelatin Nanoparticles for Lung Cancer Treatment

Abstract EN

Lung cancer has the highest mortality of any cancer worldwide, and cisplatin is a first-line chemotherapeutic agent for lung cancer treatment.

Unfortunately, cisplatin resistance is a common cause of therapeutic failure.

The ability to overcome chemoresistance is crucial to the effective treatment of lung cancer.

Recently, epigallocatechin gallate (EGCG), a type of polyphenol extracted from tea, has been shown to suppress the rapid proliferation of cancer cells, including lung cancer.

We tested whether nanoparticles (NPs) carrying a dual drug load, cisplatin and EGCG, could overcome chemoresistance to cisplatin, by working together to kill lung cancer cells.

Self-assembling gelatin/EGCG nanoparticles (GE) were synthesized, and cisplatin was then incorporated, to construct a dual drug nanomedicine (EGCG/cisplatin-loaded gelatin nanoparticle, named as GE-Pt NP).

The particle size and zeta potential were examined by dynamic light scattering (DLS).

The morphological structure of GE-Pt NPs was observed by transmission electron microscopy (TEM).

In vitro testing was performed using a human lung adenocarcinoma cell line (A549).

A cytotoxicity examination was performed, using a WST-8 cell proliferation assay.

Intracellular cisplatin content was quantified by inductively coupled plasma mass spectrometry (ICP-MS).

In conclusion, we successfully prepared GE-Pt NPs, as spherical structures, approximately 75 nm in diameter, with a positive charge (+19.83±0.25 mV).

The encapsulation rate of cisplatin in GE-Pt was about 63.7%, and the EGCG loading rate was around 89%.

A relatively low concentration of GE-Pt NPs (EGCG 5 μg/mL : cisplatin 2 μg/mL) exhibited significant cytotoxicity, compared to cisplatin alone.

The GE-Pt NPs are freely taken up by cells via endocytosis, raising the intracellular cisplatin concentration to a therapeutic level.

We consider that combination therapy of cisplatin and EGCG in nanoparticles (GE-Pt NPs) may help overcome cisplatin resistance and could effectively be used in the treatment of lung cancer.