Single peptide ligand-functionalized uniform hollow mesoporous silica nanoparticles achieving dual-targeting drug delivery to tumor cells and angiogenic blood vessel cells

Abstract

Background The purpose of this study was to construct hollow mesoporous silica nanoparticles (HMSN) decorated with tLyp-1 peptide (tHMSN) for dual-targeting drug delivery to tumor cells and angiogenic blood vessel cells. Methods HMSN were synthesized de novo using a novel cationic surfactant-assisted selective etching strategy and were then modified with tLyp-1. Multiple methods, including transmission electron microscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, bicinchoninic acid assay, and nitrogen adsorption and desorption isotherms, were used to characterize the tHMSN. Doxorubicin were chosen as the model cargo, and the uptake of doxorubicin-loaded tHMSN into MDA-MB-231 cells and human umbilical vein endothelial cells (HUVECs), as models of tumor cells and tumor neovascular endothelial cells, respectively, were observed and detected by confocal laser scanning microscopy and flow cytometry. An in vitro pharmacodynamic study and a study of the mechanism via which the nanoparticles were endocytosed were also performed. Results HMSN with a highly uniform size and well oriented mesopores were synthesized. After tHMSN were characterized, enhanced uptake of the cargo carried by tHMSN into MDA-MB-231 cells and HUVECs compared with that of their unmodified counterparts was validated by confocal laser scanning microscopy and flow cytometry at the qualitative and quantitative levels, respectively. Further, the pharmacodynamic study suggested that, compared with their unmodified counterparts, doxorubicin-loaded tHMSN had an enhanced inhibitory effect on MDA-MB-231 cells and HUVECs in vitro. Finally, a preliminary study on the mechanism by which the nanoparticles were endocytosed indicated that the clathrin-mediated endocytosis pathway has a primary role in the transport of tHMSN into the cytoplasm. Conclusion tHMSN might serve as an effective active targeting nanocarrier strategy for anti-mammary cancer drug delivery.

Time and cell‐dependent effects of endocytosis inhibitors on the internalization of biomolecule markers and nanomaterials

“…(Iversen et al, ; Johnston et al, ) To date, the standard experiments have involved the screening of cells with drug delivery nanoparticles (NPs) in the presence of endocytosis inhibitors to assess the pathways of NP internalization and trafficking. (Li et al, ; Liu et al, ; Quan et al, ) Typical inhibitor studies involve their addition to cell culture media followed by addition of labelled NPs for short periods of 1–2 hrs before obtaining a readout from, most often, flow cytometry or microscopy.…”

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

“…Besides general low-specific peptides, there have been reported other sequences with high specificity towards receptors unique to certain cell lines. This are the cases of the Interleukin targeting peptide IL-13 (VDKLLLHLKKLFREGQFNRNFESIIICRDRTC), which has been employed to target gliomas in mice [57]; the CDX (FKESWREARGTRIERG) peptide with affinity for the nicotine-acetylcholine receptors present in brain [58]; the NAPAmide (Ac-NIe-Asp-His-d-Phe-Arg-Trp-Gly-Lys-NH 2 ), an analog of the α-melanocyte stimulating hormone with great specificity towards malignant melanomas [59]; the Bld-1 (CSNRDARRC) peptide against cancerous bladder cell lines [60]; the cyclic A6 (CKPSSPPEECW) peptide able to achieve pore gating and target breast cell lines [61] and the tLyp-1 peptide (CGNKRTRGC) able to address neurophilin receptor present in many endothelial cells [62]. All those targeting peptides are summarized on Table 1.…”

Advances in mesoporous silica-based nanocarriers for co-delivery and combination therapy against cancer

“…Although this may induce tumor invasion and metastasis due to nutrient outage, a proper combination with cellular proapoptotic substances could effectively decrease its aggressiveness. to enhance penetration into tumor parenchyma and arrest tumor development (Entry 3, Table 1) [38].…”