Abstract
In recent years, supramolecular nanoparticles consisting of peptides and drugs have been regarded as useful drug delivery systems for tumor therapy. Pemetrexed (PEM) is a multitarget drug that is effective for many cancers, such as non-small cell lung cancer. Here, RGD-conjugated molecular nanoparticles mainly composed of an anticancer drug of PEM (PEM-FFRGD) were prepared to deliver PEM to tumors. The peptide could self-assemble into a nanoparticle structure with diameter of about 20 nm. Moreover, the nanoparticle showed favorable solubility and biocompatibility compared with those of PEM, and the MTT test on A549 and LLC cells showed that the PEM-FFRGD nanoparticles had stronger cytotoxic activity than PEM alone. Most importantly, the nanoparticle could promote tumor apoptosis and decrease mitochondrial energy metabolism in tumors. In vivo studies indicated that PEM-FFRGD nanoparticles had enhanced antitumor efficacy in LLC tumor-bearing mice compared to that of PEM. Our observations suggested that PEM-FFRGD nanoparticles have great practical potential for application in lung cancer therapy.
Highlights
Lung cancer is the main cause of death worldwide, with approximately 1 million cases being recorded each year (Ferlay et al, 2019)
We recently developed a self-assembling peptide (PEMFFRGD) mainly contained PEM, which was capable of forming supramolecular nanoparticles (Figure 1A) and avoiding the non-specific interactions with normal tissues
PEM could kill most cells but exhibited more green fluorescence specific to living cells than PEM-FFRGD. These results indicate that PEM-FFRGD has stronger cytotoxicity against A549 and Lewis lung cancer (LLC) cells, which may be due to the sustained release of PEM from the PEMFFRGD Gel
Summary
Lung cancer is the main cause of death worldwide, with approximately 1 million cases being recorded each year (Ferlay et al, 2019). It was reported that PEM had a therapeutic effect on colorectal tumors and lung cancer (Hanauske et al, 2001; Schaer et al, 2019). It was reported that PEM could hinder translation inhibition upon low glucose in NSCLC, and PEM combined with 2-Deoxy-glucose showed enhanced efficacy in decreasing cell proliferation of Malignant Pleural Mesothelioma (Piecyk et al, 2021). These finds suggest that PEM may have relationship with glucose metabolism. It is necessary to further investigate and improve the antitumor efficiency of PEM
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