EpCAM aptamer-functionalized polydopamine-coated mesoporous silica nanoparticles loaded with DM1 for targeted therapy in colorectal cancer

Abstract

DM1, a maytansine derivative, is a highly potential cytotoxic agent but with severe side effects; therefore, its application in clinical cancer therapy is limited. Here, in order to mitigate this intrinsic drawback of DM1, we developed mesoporous silica nanoparticles (MSNs) loaded with DM1 and surface-decorated with hydrochloride dopamine (PDA), polyethylene glycol (PEG), and epithelial cell adhesion molecule (EpCAM) aptamer (APt) for the targeted treatment of colorectal cancer (CRC). In this system, the PDA coating could be used as pH-sensitive gatekeepers to control the release of DM1 from MSNs in response to the pH stimulus and EpCAM APt-guided active targeting enables the increased delivery of DM1 to CRC as well as a reduction in toxicity and side effects by minimizing the exposure of normal tissues to DM1. Results demonstrated that DM1 inhibited the formation of microtubules and induced apoptosis in tumor cells via caspase signaling. In comparison with the control groups, the MSNs-DM1@PDA-PEG-APt bioconjugates exhibited increased binding ability and much higher cytotoxicity to the CRC SW480 cell line. Furthermore, in vivo assays confirmed the advantages of such a strategy. These findings suggested that MSNs-DM1@PDA-PEG-APt could represent a promising therapeutic platform for EpCAM-positive CRC.

Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models

“…EpCAM (CD326), a 40 kDa transmembrane glycoprotein, is overexpressed in many solid tumors, while it shows variable but generally low levels in the normal epithelium. For example, high expression of EpCAM was detected in 97.7% patients with colorectal adenocarcinoma [ 15 ]. Overexpression of EpCAM results in highly upregulated oncogene expression and promotes cell proliferation [ 16 ].…”

Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: an update

“…to SW480 [75] and DOX to SW620 colorectal cell lines [76], respectively, employing a DNA-based aptamer. Other recent examples with aptamers targeting common receptors such as mucin 1 glycoprotein [77] or CD105 [78], could be also found in the literature.…”

Mesoporous Silica Nanoparticles for Targeting Subcellular Organelles

“…Similarly, aptamers show specificity comparable to that of antibodies, albeit being non-immunogenic and easy to produce. For instance, they can be employed to functionalize the surface of MSNs for targeting the EpCAM (EpCAM aptamer) [ 37 , 38 , 39 ] and MUC1 (MUC1 aptamer) [ 40 , 41 ] proteins or the nucleolin receptor (AS1411 aptamer) [ 42 , 43 , 44 ], among others.…”