Anti‐Metastatic and Anti‐Angiogenic Activities of Core–Shell SiO₂@LDH Loaded with Etoposide in Non‐Small Cell Lung Cancer

Abstract

Currently, nanoparticles have gained a great attention in the anti‐tumor research area. However, to date, studies on the anti‐metastasis action of core–shell SiO2@LDH (LDH: layered double hydroxide) nanoparticles remain untouched. Two emerging aspects considered are establishing research on the controlling delivery effect of SiO2@LDH combined with anti‐cancer medicine from a new perspective. The fine properties synthetic SiO2@LDH‐VP16 (VP16: etoposide) are practiced to exhibit the nanoparticle's suppression on migration and invasion of non‐small cell lung cancer (NSCLC). Both in vitro and in vivo inspection shows that SiO2@LDH can help VP16 better function as an anti‐metastasis agent. On the other hand, anti‐angiogenic efficiency, co‐localization, as well as western blot are investigated to explain the possible mechanism. A clear mergence of SiO2@LDH‐VP16 and cytomembrane/microtubule may be observed from co‐location images. Results offer evidence that SiO2@LDH‐VP16 plays positions on cytomembrane and microtubules. It efficiently inhibits metastasis on NSCLC by reducing vascularization, and eliciting depression of the PI3K‐AKT and FAK‐Paxillin signaling pathways. SiO2@LDH‐VP16, the overall particle morphology, and function on anti‐metastasis and anti‐angiogenic may be tuned to give new opportunities for novel strategies for cancer therapy.

Classical VEGF, Notch and Ang signalling in cancer angiogenesis, alternative approaches and future directions

“…The AgNPs inhibit the VEGF-induced angiogenesis by blocking the formation of new microvessels through PI3K/AKT pathway inactivation ( 118 ). It has been demonstrated that the anionic clays layered double hydroxides (LDHs), a promising carrier for drug delivery according to their low cytotoxicity and high biocompatibility ( 119 ): their functionalized form with etoposide has showed anti-angiogenic activity in in vitro , ex-vivo and in vivo experimental models, eliciting depression of the PI3K-AKT and FAK-paxillin signaling pathways ( 120 ). Modified solid lipid nanoparticles loaded with paclitaxel were able to markedly reduce the tube formation in vitro and angiogenesis in vivo in glioma models ( 121 ), while, in a chorioallantoic membranes model system, pachymic acid modified multi-walled nanotubes caused a significant inhibition of angiogenesis and tube formation ( 122 ).…”

Application of multifunctional targeting epirubicin liposomes in the treatment of non-small-cell lung cancer

“…Unfortunately, the prognosis of regular chemotherapy is usually unsatisfactory due to a series of situations, including tumor metastasis, vasculogenic mimicry (VM) channels, limited killing of tumor cells, and severe systemic toxicity. 7 VM channels were first found in highly aggressive and metastatic melanoma cells in 1999. 8 Under the condition of hypoxia, tumor cells could directly form VM channels, thus facilitating tumor metastasis without the involvement of endothelial cells.…”

Etoposide Loaded SPION‐PNIPAM Nanoparticles Improve the in vitro Therapeutic Outcome on Metastatic Prostate Cancer Cells via Enhanced Apoptosis

“…[13][14][15][16] There are several studies showing that the anticancer effect of Etoposide is enhanced on different cancer cell lines using a nanoparticle delivery system. [17][18][19][20][21] Due to the hydrophobic nature of the drug PLGA and PCL were often used. For example, 11.8 micron PLGA nanoparticles loaded with Etoposide were evaluated for sustained pulmonary drug delivery.…”