scholarly journals Modeling Transmembrane Transport through Cell Membrane Wounds Created by Acoustic Cavitation

2008 ◽  
Vol 95 (9) ◽  
pp. 4124-4138 ◽  
Author(s):  
Vladimir Zarnitsyn ◽  
Christina A. Rostad ◽  
Mark R. Prausnitz
2021 ◽  
Author(s):  
Meng-meng Li ◽  
Ya Zhu ◽  
Mi Yang ◽  
Min Zheng ◽  
Haitao Ran ◽  
...  

Abstract Background: Necroptosis has emerged as a therapeutic target for stimulating antitumor immune responses in dying tumor cells. However, its suppressed expression of receptor-interacting protein kinase 3 (RIPK3), a key enzyme in necrosis in most cancer cells, limits the clinical translation to exploiting necroptosis.Design: We fabricated a multifunctional phase-transition nanoparticles platform by constructing Lip-ICG-PFP-cRGD, utilizing liposome and indocyanine green (ICG) as the shell and perfluoropentane (PFP) as the core. The platform system represented the combination of sonodynamic therapy (SDT) and immunotherapy for cancer treatment by inducing necroptosis and disrupting the cell membrane through the acoustic cavitation effect mediated by ultrasound. In addition to their inherent contrasting ability under photoacoustic imaging, our liposomes may also be used as an ultrasound imaging probe after being irradiated with low-intensity focused ultrasound (LIFU).Results: We demonstrate that nanoparticles can trigger necroptosis in ovarian cancer cells, which ruptures cell membrane by acoustic cavitation effect. When exposed to LIFU, the nanoparticles effectively facilitate the release of damage-associated molecular patterns by inducing burst-mediated cell-membrane decomposition. Moreover, the PFP phase change caused RIPK3/MLKL-independent necroptosis by acoustic cavitation effect, resulting in the release of biologically active DAMPs (CRT and HMGB1) to facilitate antitumor immunity. Therefore, necroptosis-inducible nanoparticles remarkably enhance antitumor immunity by activating CD8+ cytotoxic T cells and maturing dendritic cells in vitro. Conclusion: We have successfully synthesized Lip-ICG-PFP-cRGD nanoparticles, which can achieve SDT and provoke necroptosis by bubble-mediated cell membrane rupture. The innovative nanoparticle causes immunogenic cell death in cancer cells via RIPK3-independent necroptosis, which is a promising enhancer for cancer immunotherapy.


2012 ◽  
Vol 157 (1) ◽  
pp. 103-111 ◽  
Author(s):  
Y. Zhou ◽  
K. Yang ◽  
J. Cui ◽  
J.Y. Ye ◽  
C.X. Deng

2021 ◽  
Author(s):  
Meng-meng Li ◽  
Ya Zhu ◽  
Mi Yang ◽  
Yang Cao ◽  
Haitao Ran ◽  
...  

Abstract Background: Necroptosis has emerged as a therapeutic target for stimulating antitumor immune responses in dying tumor cells. However, its suppressed expression of receptor-interacting protein kinase 3 (RIPK3), a key enzyme in necrosis in most cancer cells, limits the clinical translation to exploiting necroptosis.Design: We fabricated a multifunctional phase-transition nanoparticles platform by constructing Lip-ICG-PFP-cRGD, utilizing liposome and indocyanine green (ICG) as the shell and perfluoropentane (PFP) as the core. The platform system represented the combination of sonodynamic therapy (SDT) and immunotherapy for cancer treatment by inducing necroptosis and disrupting the cell membrane through the acoustic cavitation effect mediated by ultrasound. In addition to their inherent contrasting ability under photoacoustic imaging, our liposomes may also be used as an ultrasound imaging probe after being irradiated with low-intensity focused ultrasound (LIFU).Results: We demonstrate that nanoparticles can trigger necroptosis in ovarian cancer cells, which ruptures cell membrane by acoustic cavitation effect. When exposed to LIFU, the nanoparticles effectively facilitate the release of damage-associated molecular patterns by inducing burst-mediated cell-membrane decomposition. Moreover, the PFP phase change caused RIPK3/MLKL-independent necroptosis by acoustic cavitation effect, resulting in the release of biologically active DAMPs (CRT and HMGB1) to facilitate antitumor immunity. Therefore, necroptosis-inducible nanoparticles remarkably enhance antitumor immunity by activating CD8+ cytotoxic T cells and maturing dendritic cells in vitro. Conclusion: We have successfully synthesized Lip-ICG-PFP-cRGD nanoparticles, which can achieve SDT and provoke necroptosis by bubble-mediated cell membrane rupture. The innovative nanoparticle causes immunogenic cell death in cancer cells via RIPK3-independent necroptosis, which is a promising enhancer for cancer immunotherapy.


Membranes ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 891
Author(s):  
Xinwei Gao ◽  
Yanfeng Liu ◽  
Jia Zhang ◽  
Luwei Wang ◽  
Yong Guo ◽  
...  

Although conventional fluorescence intensity imaging can be used to qualitatively study the drug toxicity of nanodrug carrier systems at the single-cell level, it has limitations for studying nanodrug transport across membranes. Fluorescence correlation spectroscopy (FCS) can provide quantitative information on nanodrug concentration and diffusion in a small area of the cell membrane; thus, it is an ideal tool for studying drug transport across the membrane. In this paper, the FCS method was used to measure the diffusion coefficients and concentrations of carbon dots (CDs), doxorubicin (DOX) and CDs-DOX composites in living cells (COS7 and U2OS) for the first time. The drug concentration and diffusion coefficient in living cells determined by FCS measurements indicated that the CDs-DOX composite distinctively improved the transmembrane efficiency and rate of drug molecules, in accordance with the conclusions drawn from the fluorescence imaging results. Furthermore, the effects of pH values and ATP concentrations on drug transport across the membrane were also studied. Compared with free DOX under acidic conditions, the CDs-DOX complex has higher cellular uptake and better transmembrane efficacy in U2OS cells. Additionally, high concentrations of ATP will cause negative changes in cell membrane permeability, which will hinder the transmembrane transport of CDs and DOX and delay the rapid diffusion of CDs-DOX. The results of this study show that the FCS method can be utilized as a powerful tool for studying the expansion and transport of nanodrugs in living cells, and might provide a new drug exploitation strategy for cancer treatment in vivo.


Author(s):  
M. Ashraf ◽  
L. Landa ◽  
L. Nimmo ◽  
C. M. Bloor

Following coronary artery occlusion, the myocardial cells lose intracellular enzymes that appear in the serum 3 hrs later. By this time the cells in the ischemic zone have already undergone irreversible changes, and the cell membrane permeability is variably altered in the ischemic cells. At certain stages or intervals the cell membrane changes, allowing release of cytoplasmic enzymes. To correlate the changes in cell membrane permeability with the enzyme release, we used colloidal lanthanum (La+++) as a histological permeability marker in the isolated perfused hearts. The hearts removed from sprague-Dawley rats were perfused with standard Krebs-Henseleit medium gassed with 95% O2 + 5% CO2. The hypoxic medium contained mannitol instead of dextrose and was bubbled with 95% N2 + 5% CO2. The final osmolarity of the medium was 295 M osmol, pH 7. 4.


Author(s):  
J. J. Paulin

Movement in epimastigote and trypomastigote stages of trypanosomes is accomplished by planar sinusoidal beating of the anteriorly directed flagellum and associated undulating membrane. The flagellum emerges from a bottle-shaped depression, the flagellar pocket, opening on the lateral surface of the cell. The limiting cell membrane envelopes not only the body of the trypanosome but is continuous with and insheathes the flagellar axoneme forming the undulating membrane. In some species a paraxial rod parallels the axoneme from its point of emergence at the flagellar pocket and is an integral component of the undulating membrane. A portion of the flagellum may extend beyond the anterior apex of the cell as a free flagellum; the length is variable in different species of trypanosomes.


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