Multifunctional nanocomposites DDMplusAF inhibit the proliferation and enhance the radiotherapy of breast cancer cells via modulating tumor-promoting factors and metabolic reprogramming

Abstract Background Tumor-promoting factors (TPF) and metabolic reprogramming are hallmarks of cancer cell growth. This study is designed to combine the newly synthesized two nanocomposites DDM (HA-FA-2DG@DCA@MgO) AF (HA-FA-Amygdaline@Fe 2 O 3 ) with fractionated doses radiotherapy (6 Gy-FDR; dose radiotherapy) improve efficiency chemo-radiotherapy against breast lines (BCCs; MCF-7 MDA-MB-231). The physicochemical properties each nanocomposite were confirmed using energy dispersive XRD, FTIR, HR-TEM, SEM. stability Plus was also examined, as well its release selective cellular uptake in response acidic pH. A multiple-MTT assay performed evaluate radiosensitivity BCCs at Gy (single radiotherapy; SDR) 6 Gy-FDR after 24, 48, 72 h. Finally, anti-cancer activity investigated via assessing cycle distribution apoptosis by flow cytometry, biochemical mediators (HIF-1?, TNF-?, IL-10, P53, PPAR-?, PRMT-1), along glycolytic pathway (glucose, HK, PDH, lactate, ATP) signaling effectors (protein expression AKT, AMPK, SIRT-1, TGF-?, PGC-1?, gene ERR-?) determined this study. Results verified over days without nanoparticle aggregation. selectivity data revealed that their amenable pH environment, enhanced towards owing CD44 FR-? receptors-mediated uptake. After 24 h, boosted BCC Gy-FDR. Cell arrest (G2/M pre-G1), induction, modulation TPF effectors, suppression aerobic glycolysis, all DDMPlusAF + Gy’s activity. Conclusions It could be concluded exerted a radiosensitizing efficacy targeted for therapy.