Chloroquine: a brand-new scenario for an old drug

Eftekhari, Reza Baradaran; Maghsoudnia, Niloufar; Dorkoosh, Farid Abedin

doi:10.1080/17425247.2020.1716729

Cited by 15 publications

(11 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Less than 20% of protein remained after 16 h in cells treated with 4GE11-mCherry-SC. To demonstrate that this rapid degradation was occurring in the lysosome, cells were treated with chloroquine (CQ), a weak base that prevents lysosomal acidification and, in turn, inhibits protein degradation by pH-specific enzymes . Following CQ treatment, cells were incubated with 4GE11-mCherry-SC and internalized protein was measured at 0 and 16 h post incubation.…”

Section: Resultsmentioning

confidence: 99%

“…To demonstrate that this rapid degradation was occurring in the lysosome, cells were treated with chloroquine (CQ), a weak base that prevents lysosomal acidification and, in turn, inhibits protein degradation by pHspecific enzymes. 63 Following CQ treatment, cells were incubated with 4GE11-mCherry-SC and internalized protein was measured at 0 and 16 h post incubation. From fluorescence microscopy, high levels of 4GE11-mCherry-SC remained in cells pretreated with CQ after 16 h (Figure S11).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Incorporation of Endosomolytic Peptides with Varying Disruption Mechanisms into EGFR-Targeted Protein Conjugates: The Effect on Intracellular Protein Delivery and EGFR Specificity in Breast Cancer Cells

Lieser

Chen

et al. 2022

Mol. Pharmaceutics

View full text Add to dashboard Cite

Intracellular delivery of protein therapeutics remains a significant challenge limiting the majority of clinically available protein drugs to extracellular targets. Strategies to deliver proteins to subcellular compartments have traditionally relied on cellpenetrating peptides, which can drive enhanced internalization but exhibit unreliable activity and are rarely able to target specific cells, leading to off-target effects. Moreover, few design rules exist regarding the relative efficacy of various endosomal escape strategies in proteins. Accordingly, we developed a simple fusion modification approach to incorporate endosomolytic peptides onto epidermal growth factor receptor (EGFR)-targeted protein conjugates and performed a systematic comparison of the endosomal escape efficacy, mechanism of action, and capacity to maintain EGFR-targeting specificity of conjugates modified with four different endosomolytic sequences of varying modes of action (Aurein 1.2, GALA, HA2, and L17E). Use of the recently developed Gal8-YFP assay indicated that the fusion of each endosomolytic peptide led to enhanced endosomal disruption. Additionally, the incorporation of each endosomolytic peptide increased the half-life of the internalized protein and lowered lysosomal colocalization, further supporting the membrane-disruptive capacity. Despite this, only EGFR-targeted conjugates modified with Aurein 1.2 or GALA maintained EGFR specificity. These results thus demonstrated that the choice of endosomal escape moiety can substantially affect targeting capability, cytotoxicity, and bioactivity and provided important new insights into endosomolytic peptide selection for the design of targeted protein delivery systems.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Incorporation of Endosomolytic Peptides with Varying Disruption Mechanisms into EGFR-Targeted Protein Conjugates: The Effect on Intracellular Protein Delivery and EGFR Specificity in Breast Cancer Cells

Lieser

Chen

et al. 2022

Mol. Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…Results clearly showed that the presence of chloroquine was necessary to achieve high transfection levels and, in addition, formulations with this component were well tolerated by the cells as indicated by the healthy cellular appearance along 7 days in cells exposed to formulations 1 and 2. Generally, chloroquine is considered to be cytotoxic at concentrations superior to 100 µM, while it has been reported to enhance endosomal escape of polymeric nanoparticles at a concentration of 75 µM [82]. However, in this work cells were exposed to a concentration of chloroquine of 24.23 µM, which was enough to enhance endosomal escape and far away from the cytotoxic concentration.…”

Section: Discussionmentioning

confidence: 86%

Correlation between Biophysical Properties of Niosomes Elaborated with Chloroquine and Different Tensioactives and Their Transfection Efficiency

et al. 2021

View full text Add to dashboard Cite

Lipid nanocarriers, such as niosomes, are considered attractive candidates for non-viral gene delivery due to their suitable biocompatibility and high versatility. In this work, we studied the influence of incorporating chloroquine in niosomes biophysical performance, as well as the effect of non-ionic surfactant composition and protocol of incorporation in their biophysical performance. An exhaustive comparative evaluation of three niosome formulations differing in these parameters was performed, which included the analysis of their thermal stability, rheological behavior, mean particle size, dispersity, zeta potential, morphology, membrane packing capacity, affinity to bind DNA, ability to release and protect the genetic material, buffering capacity and ability to escape from artificially synthesized lysosomes. Finally, in vitro biological studies were, also, performed in order to determine the compatibility of the formulations with biological systems, their transfection efficiency and transgene expression. Results revealed that the incorporation of chloroquine in niosome formulations improved their biophysical properties and the transfection efficiency, while the substitution of one of the non-ionic surfactants and the phase of addition resulted in less biophysical variations. Of note, the present work provides several biophysical parameters and characterization strategies that could be used as gold standard for gene therapy nanosystems evaluation.

show abstract

“…In this work, we have prepared small-sized and less polydispersed primaquine phosphate loaded PLGA nanoparticles by using nanoprecipitation method. The in vitro drug release of the nanoparticle formulation was investigated using the dialysis bag method and the release behavior was analyzed using various kinetic models such as a zero-order model, first-order model, Higuchi model, Hixson-Crowell model, and Korsmeyer-Peppas model [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and in vitro drug release of primaquine phosphate loaded PLGA nanoparticles

et al. 2021

View full text Add to dashboard Cite

Plasmodium falciparum is one of the most common resistant Plasmodium species responsible for high rates of morbidity and mortality in malaria patients. Clinical guidelines for the management of Plasmodium falciparum include the use of a dose of primaquine phosphate resulting intolerable side effects. Therefore, the aim of this work was to formulate primaquine phosphate-loaded PLGA nanoparticles by using a nanoprecipitation method in order to increase its bioavailability to minimize drug intake. This leads to reduced toxicity and better therapeutic efficacy of the drug. The synthesized nanoparticles were characterized by using dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transformed infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (XRD). TEM analysis revealed the presence of smooth spherical-shaped nanoparticles. The drug DLS analysis confirmed the presence of negatively charged nanoparticles with particle size in the range of 100-400 nm. The drug release study was performed to analyses different kinetic models like zero-order model, first-order model, Higuchi model, Hixson-Crowell model, and Korsmeyer-Peppas model.

show abstract

Chloroquine: a brand-new scenario for an old drug

Cited by 15 publications

References 31 publications

Incorporation of Endosomolytic Peptides with Varying Disruption Mechanisms into EGFR-Targeted Protein Conjugates: The Effect on Intracellular Protein Delivery and EGFR Specificity in Breast Cancer Cells

Incorporation of Endosomolytic Peptides with Varying Disruption Mechanisms into EGFR-Targeted Protein Conjugates: The Effect on Intracellular Protein Delivery and EGFR Specificity in Breast Cancer Cells

Correlation between Biophysical Properties of Niosomes Elaborated with Chloroquine and Different Tensioactives and Their Transfection Efficiency

Synthesis and in vitro drug release of primaquine phosphate loaded PLGA nanoparticles

Contact Info

Product

Resources

About