Combination Therapy With CD147‐Targeted Nanoparticles Carrying Phenformin Decreases Lung Cancer Growth

Abstract

Lung cancer is one of the most fatal cancers worldwide. Resistance to conventional therapies remains a hindrance to patient treatment. Therefore, the development of more effective anti-cancer therapeutic strategies is imperative. Solid tumors exhibit a hyperglycolytic phenotype, leading to enhanced lactate production; and, consequently, its extrusion to the tumor microenvironment. Previous data reveals that inhibition of CD147, the chaperone of lactate transporters (MCTs), decreases lactate export in lung cancer cells and sensitizes them to phenformin, leading to a drastic decrease in cell growth. In this study, the development of anti-CD147 targeted liposomes (LUVs) carrying phenformin is envisioned, and their efficacy is evaluated to eliminate lung cancer cells. Herein, the therapeutic effect of free phenformin and anti-CD147 antibody, as well as the efficacy of anti-CD147 LUVs carrying phenformin on A549, H292, and PC-9 cell growth, metabolism, and invasion, are evaluated. Data reveals that phenformin decreases 2D and 3D-cancer cell growth and that the anti-CD147 antibody reduces cell invasion. Importantly, anti-CD147 LUVs carrying phenformin are internalized by cancer cells and impaired lung cancer cell growth in vitro and in vivo. Overall, these results provide evidence for the effectiveness of anti-CD147 LUVs carrying phenformin in compromising lung cancer cell aggressiveness.

CD147/Basigin Is Involved in the Development of Malignant Tumors and T-Cell-Mediated Immunological Disorders via Regulation of Glycolysis

“…The usefulness of nanoparticles was reported. The therapeutic effect of nanoparticles carrying the anti-CD147 antibody was demonstrated in lung cancer and hepatocellular carcinoma [76][77][78]. The anti-CD147 antibody was bound to dextran nanoparticles in the trial for lung cancer [76], conjugated to liposomes for hepatoma [77], or to phosphoester polymeric nanoparticles for hepatocellular carcinoma [78].…”

“…The therapeutic effect of nanoparticles carrying the anti-CD147 antibody was demonstrated in lung cancer and hepatocellular carcinoma [76][77][78]. The anti-CD147 antibody was bound to dextran nanoparticles in the trial for lung cancer [76], conjugated to liposomes for hepatoma [77], or to phosphoester polymeric nanoparticles for hepatocellular carcinoma [78]. The possible delivery systems for compounds or antibodies targeting CD147 that will be applied in the future are summarized in Table 1.…”

Enhancing Lung Cancer Care in Portugal: Bridging Gaps for Improved Patient Outcomes

“…A late-stage diagnosis was also linked with worse survival [79]. Two other research groups have tested new therapeutic approaches, namely beta-adrenergic blockade and combination therapies using nanoparticles, to improve the therapeutic options for lung cancer patients [80,81]. Specifically, the first group evaluated the therapeutic effect of beta-blockers during immunotherapy and, although no statistically significant evidence for beta-blockers increasing immunotherapy response has been found, the modulation of the immune system with adrenergic blockage seems promising [80].…”

“…On the other hand, regarding the study on nanoparticles, its results demonstrated that anti-CD147 targeted liposomes (LUVs) carrying phenformin are effective against lung cancer cells, reducing their aggressiveness [81]. ctDNA analysis is another important area under investigation in our country.…”