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Biocompatible, Multi-Mode, Fluorescent, T 2 MRI Contrast Magnetoelectric-Silica Nanoparticles (MagSiNs), for On-Demand Doxorubicin Delivery to Metastatic Cancer Cells

Title: Biocompatible, Multi-Mode, Fluorescent, T 2 MRI Contrast Magnetoelectric-Silica Nanoparticles (MagSiNs), for On-Demand Doxorubicin Delivery to Metastatic Cancer Cells
Authors: Margo Waters; Juliane Hopf; Emma Tam; Stephanie Wallace; Jordan Chang; Zach Bennett; Hadrian Aquino; Ryan K. Roeder; Paul Helquist; M. Sharon Stack; Prakash D. Nallathamby
Source: Pharmaceuticals, Vol 15, Iss 1216, p 1216 (2022)
Publisher Information: MDPI AG
Publication Year: 2022
Collection: Directory of Open Access Journals: DOAJ Articles
Subject Terms: magnetoelectric; T 2 -contrast; fluorescent nanoparticle; cobalt ferrite; silica shell; ON-Demand drug delivery; Medicine; Pharmacy and materia medica; RS1-441
Description: There is a need to improve current cancer treatment regimens to reduce systemic toxicity, to positively impact the quality-of-life post-treatment. We hypothesized the negation of off-target toxicity of anthracyclines (e.g., Doxorubicin) by delivering Doxorubicin on magneto-electric silica nanoparticles (Dox-MagSiNs) to cancer cells. Dox-MagSiNs were completely biocompatible with all cell types and are therapeutically inert till the release of Doxorubicin from the MagSiNs at the cancer cells location. The MagSiNs themselves are comprised of biocompatible components with a magnetostrictive cobalt ferrite core (4–6 nm) surrounded by a piezoelectric fused silica shell of 1.5 nm to 2 nm thickness. The MagSiNs possess T 2 -MRI contrast properties on par with RESOVIST™ due to their cobalt ferrite core. Additionally, the silica shell surrounding the core was volume loaded with green or red fluorophores to fluorescently track the MagSiNs in vitro. This makes the MagSiNs a suitable candidate for trackable, drug nanocarriers. We used metastatic triple-negative breast cancer cells (MDAMB231), ovarian cancer cells (A2780), and prostate cancer cells (PC3) as our model cancer cell lines. Human umbilical vein endothelial cells (HUVEC) were used as control cell lines to represent blood-vessel cells that suffer from the systemic toxicity of Doxorubicin. In the presence of an external magnetic field that is 300× times lower than an MRI field, we successfully nanoporated the cancer cells, then triggered the release of 500 nM of doxorubicin from Dox-MagSiNs to successfully kill >50% PC3, >50% A2780 cells, and killed 125% more MDAMB231 cells than free Dox.HCl. In control HUVECs, the Dox-MagSiNs did not nanoporate into the HUVECS and did not exhibited any cytotoxicity at all when there was no triggered release of Dox.HCl. Currently, the major advantages of our approach are, (i) the MagSiNs are biocompatible in vitro and in vivo; (ii) the label-free nanoporation of Dox-MagSiNs into cancer cells and not the model blood vessel cell ...
Document Type: article in journal/newspaper
Language: English
Relation: https://www.mdpi.com/1424-8247/15/10/1216; https://doaj.org/toc/1424-8247; https://doaj.org/article/314d60697caa4724923b8eaafa7c2f51
DOI: 10.3390/ph15101216
Availability: https://doi.org/10.3390/ph15101216; https://doaj.org/article/314d60697caa4724923b8eaafa7c2f51
Accession Number: edsbas.81FED716
Database: BASE