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

Abstract

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.

Identification of a novel combination treatment strategy in clear cell renal cell carcinoma stem cells with shikonin and ipilimumab

“…Moreover, merging evidence showed that several phytochemicals such as curcumin, piperine, berbamine, shikonin, genistein as well as the whole extract of some plants are able to kill CSCs (19,20). For instance, epigallocatechin-3-gallate (EGCG) as an active compound in green tea is involved in several ongoing alone or combination clinical trials with cisplatin and oxaliplatin, because of the potential to suppress cancer stemness and tumorigenicity and its ability to improve the efficacy of conventional drugs in several types of cancers including RCC (21)(22)(23). The usage of phytochemicals is likely to be a potential treatment strategy for eradicating cancer through the elimination of CSCs.…”

A graphSAGE discovers synergistic combinations of Gefitinib, paclitaxel, and Icotinib for Lung adenocarcinoma management by targeting human genes and proteins: the RAIN protocol

“…Cisplatin formulations including polymeric nanoparticles, micelles, dendrimers, and liposomes have a greater chance of delivering persistent cisplatin to the growth in reaction to alterations in the tumor's microenvironment. [223][224][225][226][227] Pemetrexed is a small molecule drug that is employed in the therapy of non-squamous non-small cell lung cancer (NSCLC). It is a chemotherapeutic substance that works by inhibiting the enzymes participating in the creation of nucleotides, which are essential for DNA replication and cell division.…”

A technical note on emerging combination approach involved in the onconanotherapeutics

“…Higher cytotoxicity levels were observed in A549 cells at low drug concentrations of cisplatin at 2 μg/mL and EGCG at 5 μg/mL. At last, the researchers concluded that a combination approach of EGCG and cisplatin in NPs would be a promising anticarcinogenic candidate for treatment of lung cancer (Chen et al, 2020 ).…”