In Situ Gelation-Induced Death of Cancer Cells Based on Proteinosomes

Abstract

Hydrogels are an excellent type of material that can be utilized as a platform for cell culture. However, when a bulky hydrogel forms on the inside of cancer cells, the result would be different. In this study, we demonstrate a method for in situ gelation inside cancer cells that can efficiently induce cell death. Glutathione-responsive proteinosomes with good biocompatibility were prepared as carriers for sodium alginate to be endocytosed by cancer cells, where the chelation between sodium alginate and free calcium ions in the culture medium occurs during the diffusion process. The uptake of the hydrogel-loaded proteinosomes into the cancer cells, and then the triggered release of hydrogel with concomitant aggregation, was well-confirmed by monitoring the change of the Young's modulus of the cells based on AFM force measurements. Accordingly, when a large amount of hydrogel formed in cells, the cell viability would be inhibited by ∼90% by MTT assay at a concentration of 5.0 μM of hydrogel-loaded proteinosomes after 48 h incubation, which clearly proves the feasibility of the demonstrated method for killing cancer cells. Although more details regarding the mechanism of cell death should be conducted in the near future, such a demonstrated method of in situ gelation inside cells provides another choice for killing cancer cells.

Artificial Organelles with Orthogonal‐Responsive Membranes for Protocell Systems: Probing the Intrinsic and Sequential Docking and Diffusion of Cargo into Two Coexisting Avidin–Polymersomes

“…[19,30] Especially, the fluidity as well as multiple and different responsiveness of polymeric or lipidic membranes in cell mimics is responsible for the success in the construction of hierarchical and communicating cell compartments, [24] as well as for other membrane characteristics in diverse cell mimics without and with membrane proteins and protocells for exchanging cargo (macro)molecules. [26,29,[31][32][33][34][35][36][37][38][39][40] In eukaryotic cells, the pH value within organelles is different and partially outlines a gradient behavior (e.g., pH 7.2 for nucleus, pH range from 6.0 to 6.7 for Golgi network, and pH 4.7 for lysosome). [41] Thus, pH-responsive vesicles, [29,[42][43][44][45][46][47][48][49] used as cell mimics, are able to tune the release of cargo [42,43,[45][46][47] and the switch off and on enzymatic reactions.…”

“…[ 19,30 ] Especially, the fluidity as well as multiple and different responsiveness of polymeric or lipidic membranes in cell mimics is responsible for the success in the construction of hierarchical and communicating cell compartments, [ 24 ] as well as for other membrane characteristics in diverse cell mimics without and with membrane proteins and protocells for exchanging cargo (macro)molecules. [ 26,29,31–40 ]…”

Chemical-mediated translocation in protocell-based microactuators

“…Ultra-small proteinosomes (mean size, 2.4 μm) were prepared by sonication according to previous work. 56 In brief, proteinosomes were prepared by mixing 30 μL of an aqueous solution (pH=8.5 Na2CO3/NaHCO3 buffer containing 15 mg/mL BSA-NH2/PNIPAAm, 5, 15 or 25 mg/mL urease) and 2 mg NHS-PEG16-NHS (protein-polymer membrane crosslinker) with 2-ethyl-1-hexanol (0.5 mL) and emulsifying the mixture by sonication for 3-5 min. After 48 hours, the sedimented crosslinked proteinosomes were transferred to water by continuous washing three times with 70% ethanol/water followed by pure water.…”

Engineered borate ester conjugated protein-polymer nanoconjugates for pH-responsive drug delivery

“…proteinosome [24][25][26], and molecularly targeted nanoparticles [27,28]. Besides, they could be used to construct drug carriers, targeted-drug delivery and nanodrugs [29][30][31].…”