Cryogenic transmission electron microscopy of recombinant tuberculosis vaccine antigen with anionic liposomes reveals formation of flattened liposomes

Fox, Christopher B.; Mulligan, Sean K.; Sung, Joyce; Dowling, Quinton M.; Fung, Han Wai Millie; Vedvick, Thomas S.; Coler, Rhea N.

doi:10.2147/ijn.s56582

Cited by 29 publications

(14 citation statements)

References 27 publications

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“…18 ). The thickness of these liposomal membranes was estimated at about 5 nm, which was in accordance with the bilayer thickness of liposomes reported in the previously worked liposomes 31 , 32 . Next, we investigated the pH-responsive cleavage of DA groups from ICG/L-G2R-DA by measuring the pH-dependent change of zeta potential of samples.…”

Section: Resultssupporting

confidence: 91%

Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery

et al. 2021

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The mitochondrion is an important sub-cellular organelle responsible for the cellular energetic source and processes. Owing to its unique sensitivity to heat and reactive oxygen species, the mitochondrion is an appropriate target for photothermal and photodynamic treatment for cancer. However, targeted delivery of therapeutics to mitochondria remains a great challenge due to their location in the sub-cellular compartment and complexity of the intracellular environment. Herein, we report a class of the mitochondrion-targeted liposomal delivery platform consisting of a guanidinium-based dendritic peptide moiety mimicking mitochondrion protein transmembrane signaling to exert mitochondrion-targeted delivery with pH sensitive and charge-reversible functions to enhance tumor accumulation and cell penetration. Compared to the current triphenylphosphonium (TPP)-based mitochondrion targeting system, this dendritic lipopeptide (DLP) liposomal delivery platform exhibits about 3.7-fold higher mitochondrion-targeted delivery efficacy. Complete tumor eradication is demonstrated in mice bearing 4T1 mammary tumors after combined photothermal and photodynamic therapies delivered by the reported DLP platform.

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Section: Resultssupporting

confidence: 91%

Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery

et al. 2021

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“…The results detected by DLS and fl-NTA showed that the addition of P188 did not change the size distribution of liposomes ( Table S6 and 7 ). TEM results showed that after P188 was added to liposomes and incubated for 2 h (37°C), discontinuous segments appeared on the lipid bilayer, indicating the heterogeneity of the liposomal membrane 50 ( Figure 6C ). FRET technology was employed to investigate the structural stability of liposomes.…”

Section: Resultsmentioning

confidence: 99%

Surfactant Assisted Rapid-Release Liposomal Strategies Enhance the Antitumor Efficiency of Bufalin Derivative and Reduce Cardiotoxicity

Gao¹,

Zhang²,

He³

et al. 2021

IJN

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Background: BF211, a derivative of bufalin (BF), shows significantly improved solubility and potent antitumor efficiency compared to BF. Unfortunately, the unwanted toxicity such as cardiotoxicity caused by unspecific distribution has hindered its clinical use. Methods: PEGylated BF211 liposomes (BF211@Lipo) were designed and optimizely prepared based on the pre-prescription research. In vitro and in vivo cardiotoxicity was evaluated. In vivo pharmacokinetics and biodistribution of BF211@Lipo were investigated. In vivo antitumor activity and toxicity were evaluated in HepG2 cell xenograft models. The rapid-release triggered by Poloxamer 188 (P188) was assessed in vitro and in vivo. Results: The optimized BF211@Lipo displayed a spherical morphology with a size of (164.6 ± 10.3) nm and a high encapsulation efficiency of (93.24 ± 2.15) %. The in vivo concentration-time curves of BF211 loaded in liposomes showed a prolonged half-life in plasma and increased tumor accumulation. No obvious abnormality in electrocardiograms was observed in guinea pigs even at 9 mg/kg. Moreover, to improve the efficient release of BF211@Lipo, a surfactant-assisted rapid-release strategy was developed, and the releasepromoting mechanism was revealed by the fluorescence resonance energy transfer (FRET) and fluorescence nanoparticle tracking analysis (fl-NTA) technology. Sequential injection of BF211@Lipo and P188 could ignite the "cold" liposomes locally in tumor regions, facilitating the burst release of BF211 and enhancing the therapeutic index. Conclusion: Our progressive efforts that begin with preparation technology and dosage regimen enable BF211 to like a drug, providing a promising nano platform to deliver the cardiac glycosides and alleviate the side effects by decreasing unspecific biodistribution.

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“…The NLs suspension (4 µl) was put on a clean grid, blotted away the excess (if any) with the help of filter paper and vitrified instantly by dipping into liquid ethane. The grid was stored in liquid nitrogen till shifting under the electron microscope (Tecnai Polora, version 4.6 FEI Tecnai G2, Eindhoven, Netherlands) which was operated at 300 kV equipped with an FEI Eagle 4 K × 4 K charge-coupled device (CCD) camera for capturing the images (Fox et al., 2014 ).…”

Section: Methodsmentioning

confidence: 99%

Lipid-based nanocarrier efficiently delivers highly water soluble drug across the blood–brain barrier into brain

et al. 2018

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Delivering highly water soluble drugs across blood–brain barrier (BBB) is a crucial challenge for the formulation scientists. A successful therapeutic intervention by developing a suitable drug delivery system may revolutionize treatment across BBB. Efforts were given here to unravel the capability of a newly developed fatty acid combination (stearic acid:oleic acid:palmitic acid = 8.08:4.13:1) (ML) as fundamental component of nanocarrier to deliver highly water soluble zidovudine (AZT) as a model drug into brain across BBB. A comparison was made with an experimentally developed standard phospholipid-based nanocarrier containing AZT. Both the formulations had nanosize spherical unilamellar vesicular structure with highly negative zeta potential along with sustained drug release profiles. Gamma scintigraphic images showed both the radiolabeled formulations successfully crossed BBB, but longer retention in brain was observed for ML-based formulation (MGF) as compared to soya lecithin (SL)-based drug carrier (SYF). Plasma and brain pharmacokinetic data showed less clearance, prolonged residence time, more bioavailability and sustained release of AZT from MGF in rats compared to those data of the rats treated with SYF/AZT suspension. Thus, ML may be utilized to successfully develop drug nanocarrier to deliver drug into brain across BBB, in a sustained manner for a prolong period of time and may provide an effective therapeutic strategy for many diseases of brain. Further, many anti-HIV drugs cannot cross BBB sufficiently. Hence, the developed formulation may be a suitable option to carry those drugs into brain for better therapeutic management of HIV.

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Cryogenic transmission electron microscopy of recombinant tuberculosis vaccine antigen with anionic liposomes reveals formation of flattened liposomes

Cited by 29 publications

References 27 publications

Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery

Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery

Surfactant Assisted Rapid-Release Liposomal Strategies Enhance the Antitumor Efficiency of Bufalin Derivative and Reduce Cardiotoxicity

Lipid-based nanocarrier efficiently delivers highly water soluble drug across the blood–brain barrier into brain

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