Publication Details

Title :

Preparation of iron oxide mesoporous magnetic microparticles as novel multidrug carriers for synergistic anticancer therapy and deep tumor penetration

Journal:

Scientific Reports

Impact Factor:

4.011

Authors:

El-Boubbou K1,2, Ali R3, Al-Zahrani H3, Trivilegio T3, Alanazi AH4, Khan AL4, Boudjelal M3, AlKushi A5.

Affiliations:

1 Department of Basic Sciences, College of Science & Health Professions (COSHP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, 11481, Saudi Arabia. elboubboukh@ngha.med.sa.

2 King Abdullah International Medical Research Center (KAIMRC), King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, 11426, Saudi Arabia. elboubboukh@ngha.med.sa.

3 King Abdullah International Medical Research Center (KAIMRC), King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, 11426, Saudi Arabia.

4 Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, 11426, Saudi Arabia.

5Department of Basic Sciences, College of Science & Health Professions (COSHP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, 11481, Saudi Arabia.

Year of Publication:

2019

DOI:

10.1038/s41598-019-46007-z.

Abstract:

The preparation of mesoporous iron oxides with controllable physiochemical properties for effective therapeutic drug delivery remains a formidable challenge. Herein, iron oxide mesoporous magnetic microparticles (IO-MMMs) were prepared by a modified reverse hard-templating approach using, for the first time, acid-prepared mesoporous spheres (APMS) as the hard silica template. The obtained mesostructures exhibited remarkably high surface area and large pore volumes (SBET = 240 m2/g and Vpore = 0.55 cm3/g), controllable average sizes, generally uniform morphologies, and excellent biocompatibilities, allowing them to achieve optimal drug release in cancer cells and tumor tissues. IO-MMM carriers were able to co-load high amounts of hydrophilic chemotherapeutic drugs (Dox or Daun) and/or hydrophobic hormonal anticancer drugs (Tam), and release them sustainably in a pH-dependent manner, utilizing the fluorescence of Daun to real-time trace the intracellular drug distribution, and employing Daun/Tam to treat cancer by combined chemo/hormonal therapy. Cytotoxicity assays against different types of cancerous cells showed that the combinatory Daun/Tam@IO-MMM formulation significantly reduced the viability of metastatic MCF7 and KAIMRC1 breast as well as HCT8 colorectal cancer cells, with the least potency towards non-cancerous normal primary cells (up to 10-fold). Electron, flow, and live confocal microscopy imaging confirmed that the loaded vehicles were successfully and differentially uptaken by the different tested cells, gradually releasing their payloads, and causing apoptotic cell death. Importantly, compared to free drugs, Daun/Tam@IO-MMMs displayed enhanced drug accumulation in patient breast primary tumor tissues, deeply penetrating into the tumor region and killing the tumor cells inside. The designed carriers described here, thus, constitute a novel promising magnetic mesoporous smart system that entraps different kinds of drugs and release them in a controlled manner for combinatorial chemo/hormonal cancer theranostics. This multifactorial platform may open new avenues in cancer therapy as efficient synergistic antitumor system through overcoming limitations of conventional cancer therapy.