Cancer‐Cell‐Derived Hybrid Vesicles from MCF‐7 and HeLa Cells for Dual‐Homotypic Targeting of Anticancer Drugs

Abstract

Here, as a proof of concept, hybrid vesicles (VEs) are developed from two types of cancer cells, MCF-7 and HeLa, for the dual targeting of the anticancer drug doxorubicin (Dox) to cancer cells via homotypic interactions. Hybrid VEs with a size of 181.8 ± 28.2 nm and surface charge of −27.8 ± 1.9 mV are successfully prepared by the fusion of MCF-7 and HeLa VEs, as demonstrated by the fluorescence resonance energy transfer assay. The hybrid VEs exhibit enhanced intracellular uptake both in MCF-7 and HeLa cells. Dox-encapsulated hybrid VEs (Dox-hybrid VEs) also exhibit promising anticancer and antiproliferative activities against MCF-7/multidrug-resistant cells and HeLa cells. In addition, compared to free Dox, the Dox-hybrid VEs exhibit low intracellular uptake and reduced cytotoxicity for RAW264.7 cells. Thus, hybrid VEs with dual-targeting activity toward two types of cancer cells may be useful for the specific targeting of anticancer drugs for improved anticancer effects with reduced nonspecific toxicity.

Interaction of Near-Infrared (NIR)-Light Responsive Probes with Lipid Membranes: A Combined Simulation and Experimental Study

“…Moreover, the CBF loading reached 202 µg of CBF per mg of RBC-membrane-derived vesicles and an encapsulation efficiency of 17%. These values are in accordance with the data available in the literature for RBC membrane-derived vesicles prepared with a similar methodology [ 71 , 72 , 73 ]. As shown in Figure 8 , the membrane leakage in the presence of IR780 and IR820 was followed over time and for different concentrations of each NIR molecule.…”

Current Strategies for Cancer Cell-Derived Extracellular Vesicles for Cancer Therapy

“…The main strategies for CEVs generation have been summarized in four categories, including irradiated CEVs, advanced materials-combined CEVs, chemotherapeutic drug-loaded CEVs, and genetically engineered CEVs (Table 1). Along with the increasing challenges and The engulfing process of drugs is conducted via the incubation of cancers cells with drugs so as to release drug-loaded CEVs (21-23, 25, 51) Co-extrusion of the mixture of CEVs and drugs was performed after the centifugation and incubation of the mixture at 4 o C (19) The CEVs and drugs were incubated in saponin at 37 o C (65) the Freeze-thaw cycles was performed after the stirring process of CEVs and drugs (62) The CEVs were incubated with drugs at 22 o C or 37 o C in the solution of drugs (67) The drugs-loaded CEVs containing supernatants were received a and repeated and sequential utracentrifugation (21-23, 25, 51) The excess drugs was removed by filtering through an Amicon Ultra-15 100 kDa filter (19) The extral drugs and saponin were remove with Nanosep device (65) The mixtures of drugs-CEVs were filter through protein concentrators(MicroSep Centrifugal Devices 10k) at 2,000x g for 10 min (62) Repeated utracentrifugation (67) (up to 170,000 g for 120 min)…”

“…As the EVs are processed and generated, CEVs are released and packed with chemotherapeutic drugs in the supernatant of cancer cells (21-23, 25, 51, 64). In other studies, the drug-loaded CEVs were mainly prepared in two steps: the first step involved the isolation of CEVs, and the second step involved drug loading (19,26,(65)(66)(67). The first step of isolation was conducted mainly via the traditional ultracentrifugation.…”

Cell Membrane-Derived Vesicle: A Novel Vehicle for Cancer Immunotherapy

“…Another important rationale for employing cancer cell vesicles as antitumor drug vehicles is homotypic targeting, which is probably through surface adhesion molecules such as N-cadherin and galectin-3 ( 28 , 29 ). In a tumor self-targeting study, researchers prepared four kinds of cell membrane-encapsulated magnetic nanoparticles derived from different tumor cell lines.…”

“…Fused or hybridized cellular vesicles can be produced by breaking up, mixing and then co-extruding through polycarbonate porous membranes. A large number of works have investigated the fusion of two or even more types of cell membrane vesicles to achieve multi-functionality ( 10 , 14 , 29 , 59 ).…”