Dataset Information

Bortezomib-Loaded Mesoporous Silica Nanoparticles Selectively Alter Metabolism and Induce Death in Multiple Myeloma Cells.

ABSTRACT: A mesoporous silica-based nanodevice bearing the antineoplastic drug bortezomib (BTZ), whose release is triggered in acidic environment and grafted with folic acid (FOL) as a targeting function (FOL-MSN-BTZ) was tested on folate receptor overexpressing (FR+) multiple myeloma (MM) cells and on FR negative (FR-) normal cells. FOL-MSN-BTZ efficacy studies were conducted by means of growth experiments, TEM, TUNEL assay and Western Blotting analysis (WB). Metabolic investigations were performed to assess cells metabolic response to MSNs treatments. FOL-MSN-BTZ exclusively killed FR+ MM cells, leading to an apoptotic rate that was comparable to that induced by free BTZ, and the effect was accompanied by metabolic dysfunction and oxidative stress. Importantly, FOL-MSN-BTZ treated FR- normal cells did not show any significant sign of injury or metabolic perturbation, while free BTZ was still highly toxic. Notably, the vehicle alone (MSN-FOL) did not affect any biological process in both tested cell models. These data show the striking specificity of FOL-MSN-BTZ toward FR+ tumor cells and the outstanding safety of the MSN-FOL vehicle, paving the way for a future exploitation of FOL-MSN-BTZ in MM target therapy.

SUBMITTER: Nigro A

PROVIDER: S-EPMC7565423 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bortezomib-Loaded Mesoporous Silica Nanoparticles Selectively Alter Metabolism and Induce Death in Multiple Myeloma Cells.

Nigro Alessandra A Frattaruolo Luca L Fava Mariarosa M De Napoli Ilaria I Greco Marianna M Comandè Alessandra A De Santo Marzia M Pellegrino Michele M Ricci Elena E Giordano Francesca F Perrotta Ida I Leggio Antonella A Pasqua Luigi L Sisci Diego D Cappello Anna Rita AR Morelli Catia C

Cancers 20200921 9

A mesoporous silica-based nanodevice bearing the antineoplastic drug bortezomib (BTZ), whose release is triggered in acidic environment and grafted with folic acid (FOL) as a targeting function (FOL-MSN-BTZ) was tested on folate receptor overexpressing (FR+) multiple myeloma (MM) cells and on FR negative (FR-) normal cells. FOL-MSN-BTZ efficacy studies were conducted by means of growth experiments, TEM, TUNEL assay and Western Blotting analysis (WB). Metabolic investigations were performed to as ...[more]

PMID: 32967380

Similar Datasets

Project description:Simple Summary The combination of guanidine carbonate and curcumin-loaded hollow mesoporous silica nanoparticles (GuC-HMSNAP) can be used as a therapeutic and to induce MCF-7 cell death. Due to its biological safety and high drug loading capacity, HMSNAP is becoming an increasingly important nanocarrier for cancer research. The features of drug-loaded nanocarriers are significantly altered particle size, pore size, surface area, and pore volume, confirming that a significant amount of drugs can be loaded in the nanocarriers while simultaneously allowing the maximum amount of drugs to be released from the nanocarriers. Here, guanidine-mediated apoptosis is analysed through western blotting; the results suggest that drug complexes result in downregulation of phosphorylation in Ser471 of Akt, Ser259 of c-Raf, and Ser241 of PDK1, upregulation of phosphorylation in GSK-3β Ser9, cleaved caspases, and cleaved PARP, which then partially induces intrinsic cell death in MCF-7. As a whole, our results demonstrate that GuC-HMNSAP is an efficient nanocarrier for effectively inducing cancer cell death. Abstract The current study focuses on developing a tumour-targeted functionalised nanocarrier that wraps hollow mesoporous silica nanoparticles. The guanidine carbonate and curcumin are immobilised on the surface of 3-aminopropyl-triethoxy silane (APTES)-decorated hollow mesoporous silica nanoparticles (HMSNP), as confirmed through XPS and NMR analysis. XPS analysis demonstrates that the shape of the hysteresis loops is modified and that pore volume and pore diameter are consequently decreased compared to control. Guanidine (85%) and guanidine–curcumin complex (90%) were successfully encapsulated in HMSNAP and showed a 90% effective and sustained release at pH 7.4 for up to 72 h. Acridine orange/ethidium bromide dual staining determined that GuC-HMNSAP induced more late apoptosis and necrosis at 48 and 72 h compared with Gu-HMNSAP-treated cells. Molecular investigation of guanidine-mediated apoptosis was analysed using western blotting. It was found that cleaved caspases, c-PARP, and GSK-3β (Ser9) had increased activity in MCF-7 cells. GuC-HMSNAP increased the activity of phosphorylation of oncogenic proteins such as Akt (Ser473), c-Raf (Ser249), PDK1 (Ser241), PTEN (Ser380), and GSK-3β (Ser9), thus inducing cell death in MCF-7 cells. Altogether, our findings confirm that GuC-HMNSAP induces cell death by precisely associating with tumour-suppressing proteins, which may lead to new therapeutic approaches for breast cancer therapy.

Dataset Information

Bortezomib-Loaded Mesoporous Silica Nanoparticles Selectively Alter Metabolism and Induce Death in Multiple Myeloma Cells.

Publications

Bortezomib-Loaded Mesoporous Silica Nanoparticles Selectively Alter Metabolism and Induce Death in Multiple Myeloma Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets