Carrier-free highly drug-loaded biomimetic nanosuspensions encapsulated by cancer cell membrane based on homology and active targeting for the treatment of glioma

Abstract

Nanosuspensions, as a new drug delivery system for insoluble drugs, are only composed of a drug and a small amount of stabilizer, which is dispersed in an aqueous solution with high drug-loading, small particle size, high dispersion, and large specific surface area. It can significantly improve the dissolution, bioavailability, and efficacy of insoluble drugs. In this study, paclitaxel nanosuspensions ((PTX)NS) were prepared by an ultrasonic precipitation method, with the characteristics of simple preparation and easy repetition. With the help of a homologous targeting mechanism, a kind of glioma C6 cancer cell membrane (CCM)-coated (PTX)NS was developed and modified with D WSW peptide to obtain D WSW-CCM-(PTX)NS with the functions of BBB penetration and tumor targeting. The results showed that the cancer cell membrane could effectively camouflage the nanosuspensions so that it was not cleared by the immune system and could cross the blood-brain-barrier (BBB) and selectively target tumor tissues. Cell uptake experiments and in vivo imaging confirmed that the uptake of D WSW-CCM-(PTX)NS by tumor cells and the distribution in intracranial gliomas increased. Cytotoxicity test and in vivo anti-glioma studies showed that D WSW-CCM-(PTX)NS could significantly inhibit the growth of glioma cells and significantly prolong the survival time of glioma-bearing mice. Finally, the cancer cell membrane coating endowed the nanosuspensions with the biological properties of homologous adhesion and immune escape. This study provides an integrated solution for improving the targeting of nanosuspensions and demonstrates the encouraging potential of biomimetic nanosuspensions applicable to tumor therapy.

Uptake of oxidative stress-mediated extracellular vesicles by vascular endothelial cells under low magnitude shear stress

“…The biodistribution and uptake of nanoparticles by cells can determine their therapeutic efficacy and toxicity in vivo [ [46] , [47] , [48] ] . In previous reports, the interaction of synthetic nanoparticles with cells and their distribution in the blood circulation system were well investigated in vitro cell experiments and some animal models [ 49 , 50 ].…”

Hybrid membrane-coated nanosuspensions for multi-modal anti-glioma therapy via drug and antigen delivery

“…An intracranial glioma-bearing mouse model was established according to previously described procedures [ 46 ]. After anesthetizing C6 cells with chloral hydrate (4%, w/v%), 2 μL of the cells at a density of 2 × 10 6 were injected into the right striatum (1.8 mm lateral, 1 mm longitudinal, and 4 mm depth) of ICR mice.…”

Novel brain-targeted nanomicelles for anti-glioma therapy mediated by the ApoE-enriched protein corona in vivo

“…To synthesize the Aβ-CN-modified targeted carrier, the Aβ-CN peptide with an additional cysteine in its N-terminus was coupled to the terminal mal groups of Mal-PEG 2000 –PLA 1300 using the Michael addition reaction, as described in the previous section [ 29 – 31 ]. First, Mal-PEG 2000 –PLA 1300 was mixed with an aqueous solution of Aβ-CN to form a suspension.…”

“…Two days later, the apical culture medium was replaced and HUVECs were incubated with free Cou-6, Cou-6/PMs, Cou-6/Aβ-CN-PMs, and rhApoE/Cou-6/Aβ-CN-PMs for 3 h. After incubation, the C6 cells in the lower chamber were washed with cold PBS thrice and fixed with 4% paraformaldehyde for 15 min. The C6 cell nuclei were then stained with DAPI, and the BBTB penetration and targeting ability of Aβ-CN-PMs were analyzed using CLSM [ 3 , 29 , 36 ]. For quantitative analysis, the fluorescence intensity of the C6 cells was determined through flow cytometry using the same experimental steps as described above in “ Cellular uptake assays ” section.…”