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Mesoporous silica nanoparticles as a breast-cancer targeting ultrasound contrast agent.

ABSTRACT: Ultrasound (US) is used widely in the context of breast cancer. While it is advantageous for a number of reasons, it has low specificity and requires the use of a contrast agent. Its use as a standalone diagnostic and real-time imaging modality could be achieved by development of a tumor-targeted ultrasound contrast agent (UCA); functionalizing the UCA with a tumor-targeting agent would also allow the targeted administration of anti-cancer drugs at the tumor site. In this article, clinical US techniques are used to show that mesoporous silica nanoparticles (MSNs), functionalized with the monoclonal antibody Herceptin(®), can be used as an effective UCA by increasing US image contrast. Furthermore, in vitro assays show the successful localization and binding of the MSN-Herceptin conjugate to HER2+ cancer cells, resulting in tumor-specific cytotoxicity. These results demonstrate the potential of MSNs as a stable, biocompatible, and effective therapeutic and diagnostic ("theranostic") agent for US-based breast cancer imaging, diagnosis, and treatment.

SUBMITTER: Milgroom A

PROVIDER: S-EPMC4687408 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Mesoporous silica nanoparticles as a breast-cancer targeting ultrasound contrast agent.

Milgroom Andrew A Intrator Miranda M Madhavan Krishna K Mazzaro Luciano L Shandas Robin R Liu Bolin B Park Daewon D

Colloids and surfaces. B, Biointerfaces 20131101

Ultrasound (US) is used widely in the context of breast cancer. While it is advantageous for a number of reasons, it has low specificity and requires the use of a contrast agent. Its use as a standalone diagnostic and real-time imaging modality could be achieved by development of a tumor-targeted ultrasound contrast agent (UCA); functionalizing the UCA with a tumor-targeting agent would also allow the targeted administration of anti-cancer drugs at the tumor site. In this article, clinical US te ...[more]

PMID: 24269054

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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

Mesoporous silica nanoparticles as a breast-cancer targeting ultrasound contrast agent.

Publications

Mesoporous silica nanoparticles as a breast-cancer targeting ultrasound contrast agent.

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