Improving anti-cancer drug delivery performance of magnetic mesoporous silica nanocarriers for more efficient colorectal cancer therapy

Abstract

Background Improving anti-cancer drug delivery performance can be achieved through designing smart and targeted drug delivery systems (DDSs). For this aim, it is important to evaluate overexpressed biomarkers in the tumor microenvironment (TME) for optimizing DDSs. Materials and methods Herein, we designed a novel DDS based on magnetic mesoporous silica core–shell nanoparticles (SPION@MSNs) in which release of doxorubicin (DOX) at the physiologic pH was blocked with gold gatekeepers. In this platform, we conjugated heterofunctional polyethylene glycol (PEG) onto the outer surface of nanocarriers to increase their biocompatibility. At the final stage, an epithelial cell adhesion molecule (EpCAM) aptamer as an active targeting moiety was covalently attached (Apt-PEG-Au@NPs-DOX) for selective drug delivery to colorectal cancer (CRC) cells. The physicochemical properties of non-targeted and targeted nanocarriers were fully characterized. The anti-cancer activity, cellular internalization, and then the cell death mechanism of prepared nanocarriers were determined and compared in vitro. Finally, tumor inhibitory effects, biodistribution and possible side effects of the nanocarriers were evaluated in immunocompromised C57BL/6 mice bearing human HT-29 tumors. Results Nanocarriers were successfully synthesized with a mean final size diameter of 58.22 ± 8.54 nm. Higher cytotoxicity and cellular uptake of targeted nanocarriers were shown in the EpCAM-positive HT-29 cells as compared to the EpCAM-negative CHO cells, indicating the efficacy of aptamer as a targeting agent. In vivo results in a humanized mouse model showed that targeted nanocarriers could effectively increase DOX accumulation in the tumor site, inhibit tumor growth, and reduce the adverse side effects. Conclusion These results suggest that corporation of a magnetic core, gold gatekeeper, PEG and aptamer can strongly improve drug delivery performance and provide a theranostic DDS for efficient CRC therapy. Graphic abstract

Anti‐CD63‐Oligonucleotide Functionalized Magnetic Beads for the Rapid Isolation of Small Extracellular Vesicles and Detection of EpCAM and HER2 Membrane Receptors using DARPin Probes

“…Our investigation of MCF7 and MDA‐MB‐231 cells revealed significantly lower EpCAM protein expression in the membrane of MDA‐MB‐231 cells (Figure S1) confirming the lack of EpCAM protein in the membrane of sEVs isolated from this cell line. Low expression of EpCAM by human MDA‐MB‐231 cells and hamster CHO cells was also reported previously by others confirming our results [39,40,41] …”

“…Low expression of EpCAM by human MDA-MB-231 cells and hamster CHO cells was also reported previously by others confirming our results. [39,40,41] Figure 3a shows a 1000-fold increase in fluorescence above background upon binding of OligoCy5 to streptavidin-conjugated MB. Flow cytometry binding of anti-EpCAM DARPin to MCF7 sEVs and Plasma sEVs revealed a 10-fold increase in fluorescence above background.…”

Using magnetic mesoporous silica nanoparticles armed with EpCAM aptamer as an efficient platform for specific delivery of 5-fluorouracil to colorectal cancer cells

“…The release profile of 5-FU from Au-NPs@5-FU comprises two fast and slow phases, as illustrated in Figure 4F, which is consistent with many other studies (Babaei et al, 2017;Iranpour et al, 2021b). Encapsulation of 5-FU within porous silica was intended to prolong the residence time of the drug inside the body and thereby to improve the cellular uptake of the drug by cancer cells.…”

“…Then, 5 ml of icecold fresh 0.1 M NaBH 4 was added to the solution while vigorously rousing. The solution turned pink immediately after adding NaBH 4 , demonstrating the formation of gold nanoparticles (Iranpour et al, 2021b). In the next step, 1 ml of prepared gold NPs were added to 2 mg/ml of previous step products and stirred for 24 h at room temperature.…”

Immunotherapy-based novel nanoparticles in the treatment of gastrointestinal cancer: Trends and challenges

“…Furthermore, due to their simple production process and high drug loading efficiency, polymersomes are also considered candidate nanoparticles for clinical translation[ 35 - 37 ]. There are also many kinds of novel nanoparticles, such as gold nanoparticles, manganese dioxide nanoparticles, upconversion nanoparticles (UCNPs), metal organic framework nanoparticles and mesoporous silica nanoparticles (MSNPs), which can also play important roles in different diseases or cancers through their own characteristics[ 38 - 42 ]. Here, among the GICs, we focus on GC, HCC, CRC and pancreatic cancer and summarize the application trends of immunotherapy-based novel nanoparticles in these cancers as well as the challenges and opportunities in the future.…”