The Effect of Surface Charges on the Cellular Uptake of Liposomes Investigated by Live Cell Imaging

Kang, Ji Hee; Jang, Woo Young; Ko, Young Tag

doi:10.1007/s11095-017-2097-3

Cited by 87 publications

(61 citation statements)

References 39 publications

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“…The presence of a positive charge on the liposomal surface incorporates a greater capacity to be internalized due to their potential interaction with the negatively charged cell membrane [59]. In a recent study by Kang et al, it was reported that cationic liposomes exhibited higher uptake due to their potential electrostatic interaction with cells [60]. The results of our cellular uptake studies were in agreement with these findings.…”

Section: Discussionsupporting

confidence: 91%

Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment

et al. 2020

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Non-small cell lung cancer (NSCLC) is a global disorder, treatment options for which remain limited with resistance development by cancer cells and off-target events being major roadblocks for current therapies. The discovery of new drug molecules remains time-consuming, expensive, and prone to failure in safety/efficacy studies. Drug repurposing (i.e., investigating FDA-approved drug molecules for use against new indications) provides an opportunity to shorten the drug development cycle. In this project, we propose to repurpose pirfenidone (PFD), an anti-fibrotic drug, for NSCLC treatment by encapsulation in a cationic liposomal carrier. Liposomal formulations were optimized and evaluated for their physicochemical properties, in-vitro aerosol deposition behavior, cellular internalization capability, and therapeutic potential against NSCLC cell lines in-vitro and ex-vivo. Anti-cancer activity of PFD-loaded liposomes and molecular mechanistic efficacy was determined through colony formation (1.5- to 2-fold reduction in colony growth compared to PFD treatment in H4006, A549 cell lines, respectively), cell migration, apoptosis and angiogenesis assays. Ex-vivo studies using 3D tumor spheroid models revealed superior efficacy of PFD-loaded liposomes against NSCLC, as compared to plain PFD. Hence, the potential of inhalable liposome-loaded pirfenidone in NSCLC treatment has been established in-vitro and ex-vivo, where further studies are required to determine their efficacy through in vivo preclinical studies followed by clinical studies.

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Section: Discussionsupporting

confidence: 91%

Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment

et al. 2020

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“…Although in the present work the endocytic mechanisms were not investigated, we speculate that the difference in the extent of internalisation between the free prodrug and the pH-sensitive liposomes could rely on the involvement of distinct uptake modalities and/or kinetics of intracellular processing. There is compelling evidence showing that liposome/nanoparticle uptake is influenced by a multitude of parameters, including nanocarrier size 52,54 , surface charge 55,56 and hydrophobicity 56,57 , lipid composition 58,59 , shape 53,56 and cell type 53,54 .…”

Section: Discussionmentioning

confidence: 99%

Intracellular Activation of a Prostate Specific Antigen-Cleavable Doxorubicin Prodrug: A Key Feature Toward Prodrug-Nanomedicine Design

et al. 2019

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was in phase I clinical trials for patients with metastatic castration-resistant prostate cancer (mCRPC). It consists of doxorubicin (Dox) conjugated to a prostate specific antigen (PSA)-cleavable peptide that can be selectively activated by secreted PSA at the tumor site. However, despite the initial promising results, further clinical testing with Dox-PSA was halted due to toxicity concerns emerging from non-PSA-specific cleavage, following systemic administration.In the present study, we have reported, for the first time, the intracellular activation of Dox-PSA, where Dox nuclear uptake was specific to C4-2B (PSA-expressing) cells, which agreed with the cytotoxicity studies. This finding was confirmed by encapsulating Dox-PSA prodrug into pH-sensitive liposomes to enable prodrug intracellular release, followed by its enzymatic activation. Interestingly, our results demonstrated that Dox-PSA loaded into pH-responsive nanoparticles exhibited cytotoxicity comparable to free prodrug in C4-2B monolayers, with superior activity in tumor spheroids, due to deeper penetration within tumor spheroids. Our approach could open the doors for novel Dox-PSA nanomedicines with higher safety and efficacy to treat advanced and metastatic prostate cancer.

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“…The zeta potential was 16.6 ± 1.7 mV before the addition of heparin and decreased to 11.8 ± 1.4 mV after heparin electrostatic bonding. The fact that the charge remained positive, making this a cationic liposome, is an advantage, because these are preferably endocytosed by targeted cells as they are more attracted by the negatively charged cell membrane, improving the cellular concentration of the molecule of interest [20,21].…”

Section: Resultsmentioning

confidence: 99%

Heparin-Coated Liposomes Improve Antiplasmodial Activity and Reduce the Toxicity of Poupartone B

Ledoux

Mamede

Palazzo

et al. 2020

Planta Medica International Open

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Poupartone B is an alkyl cyclohexenone derivative isolated from Poupartia borbonica. This compound demonstrated promising antimalarial activity (IC50 < 1 µg/mL), however, it was not devoid of toxicity. Thus, to reduce the adverse side effects of this natural bioactive molecule, a delivery strategy involving a nanostructure was formulated. Additionally, poupartone B-loaded liposomes were coated with heparin, a glycosaminoglycan that is known to target proteins on the surface of Plasmodium falciparum-infected red blood cells. The quantification of the compound in the formulation was performed by HPLC-DAD, while heparin was quantitated by 1H NMR spectroscopy. The liposomes’ antiplasmodial activity was tested on artemisinin-resistant P. falciparum isolate, and toxicity was evaluated on human HeLa cells and zebrafish embryos. Throughout this research, the formulation demonstrated higher antiplasmodial activities against both P. falciparum strains and a significant decrease of in vitro toxicity. The formulation improved the selectivity index 2 times in vitro and proved to be 3 times less toxic than the compound alone in the zebrafish embryo acute toxicity test. Hence, the use of this strategy to deliver natural products in Plasmodium-infected cells, particularly those with a narrow therapeutic margin, is proposed.

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The Effect of Surface Charges on the Cellular Uptake of Liposomes Investigated by Live Cell Imaging

Abstract: This study provides a better understanding on the cellular uptake mechanisms of the liposomes, which could contribute significantly to development of liposome-based drug delivery systems.

Cited by 87 publications

References 39 publications

Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment

Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment

Intracellular Activation of a Prostate Specific Antigen-Cleavable Doxorubicin Prodrug: A Key Feature Toward Prodrug-Nanomedicine Design

Heparin-Coated Liposomes Improve Antiplasmodial Activity and Reduce the Toxicity of Poupartone B

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