Acidic pH-Responsive siRNA Conjugate for Reversible Carrier Stability and Accelerated Endosomal Escape with Reduced IFNα-Associated Immune Response

2013 ◽  
Vol 125 (24) ◽  
pp. 6338-6341 ◽  
Author(s):  
Hiroyasu Takemoto ◽  
Kanjiro Miyata ◽  
Shota Hattori ◽  
Takehiko Ishii ◽  
Tomoya Suma ◽  
...  
Keyword(s):  
Immune Response ◽  
Endosomal Escape ◽  
Acidic Ph ◽  
Ph Responsive

Acidic pH-Responsive siRNA Conjugate for Reversible Carrier Stability and Accelerated Endosomal Escape with Reduced IFNα-Associated Immune Response

2013 ◽  
Vol 52 (24) ◽  
pp. 6218-6221 ◽  
Author(s):  
Hiroyasu Takemoto ◽  
Kanjiro Miyata ◽  
Shota Hattori ◽  
Takehiko Ishii ◽  
Tomoya Suma ◽  
...  
Keyword(s):  
Immune Response ◽  
Endosomal Escape ◽  
Acidic Ph ◽  
Ph Responsive

Acidic pH-responsive changes of DNA structure and surface dynamics as probed with ultrasensitive Raman spectroscopy

2021 ◽  
Vol 258 ◽  
pp. 119866
Author(s):  
Cristina M. Muntean ◽  
Nicoleta E. Dina ◽  
Ioan Bratu ◽  
Carmen Tripon ◽  
Sorina Niţu (Năstase) ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Dna Structure ◽  
Acidic Ph ◽  
Surface Dynamics ◽  
Ph Responsive

pH-responsive cationic liposome for endosomal escape mediated drug delivery

2020 ◽  
Vol 188 ◽  
pp. 110804 ◽  
Author(s):  
Sagar Rayamajhi ◽  
Jessica Marchitto ◽  
Tuyen Duong Thanh Nguyen ◽  
Ramesh Marasini ◽  
Christian Celia ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cationic Liposome ◽  
Endosomal Escape ◽  
Ph Responsive

A versatile pH-responsive platform for intracellular protein delivery using calcium phosphate nanoparticles

2015 ◽  
Vol 3 (47) ◽  
pp. 9115-9121 ◽  
Author(s):  
Bingru Zeng ◽  
Hongdong Shi ◽  
Yangzhong Liu
Keyword(s):  
Calcium Phosphate ◽  
Protein Delivery ◽  
Intracellular Delivery ◽  
Endosomal Escape ◽  
Ph Responsive ◽  
Intracellular Protein ◽  
Calcium Phosphate Nanoparticles ◽  
Intracellular Protein Delivery

A highly biocompatible nanoplatform for the intracellular delivery of different proteins, exhibiting pH-responsive release and efficient endosomal escape.

scholarly journals Multivalent dendritic polyglycerolamine with arginine and histidine end groups for efficient siRNA transfection

2015 ◽  
Vol 11 ◽  
pp. 763-772 ◽  
Author(s):  
Fatemeh Sheikhi Mehrabadi ◽  
Hanxiang Zeng ◽  
Mark Johnson ◽  
Cathleen Schlesener ◽  
Zhibin Guan ◽  
...  
Keyword(s):  
Amino Acid ◽  
Transfection Efficiency ◽  
Endosomal Escape ◽  
Primary Amines ◽  
Ph Responsive ◽  
3T3 Cells ◽  
Sirna Transfection ◽  
Efficient Delivery ◽  
End Groups ◽  
Nih 3T3

The success of siRNA-based therapeutics highly depends on a safe and efficient delivery of siRNA into the cytosol. In this study, we post-modified the primary amines on dendritic polyglycerolamine (dPG-NH2) with different ratios of two relevant amino acids, namely, arginine (Arg) and histidine (His). To investigate the effects from introducing Arg and His to dPG, the resulting polyplexes of amino acid functionalized dPG-NH2s (AAdPGs)/siRNA were evaluated regarding cytotoxicity, transfection efficiency, and cellular uptake. Among AAdPGs, an optimal vector with (1:3) Arg to His ratio, showed efficient siRNA transfection with minimal cytotoxicity (cell viability ≥ 90%) in NIH 3T3 cells line. We also demonstrated that the cytotoxicity of dPG-NH2 decreased as a result of amino acid functionalization. While the incorporation of both cationic (Arg) and pH-responsive residues (His) are important for safe and efficient siRNA transfection, this study indicates that AAdPGs containing higher degrees of His display lower cytotoxicity and more efficient endosomal escape.

scholarly journals PAC1, a pH-Regulatory Gene from Fusarium verticillioides

2003 ◽  
Vol 69 (9) ◽  
pp. 5222-5227 ◽  
Author(s):  
Joseph E. Flaherty ◽  
Anna Maria Pirttilä ◽  
Burton H. Bluhm ◽  
Charles P. Woloshuk
Keyword(s):  
Fusarium Verticillioides ◽  
Regulatory Gene ◽  
Synthetic Medium ◽  
Transcriptional Regulators ◽  
Acidic Ph ◽  
Alkaline Ph ◽  
Wild Type ◽  
Ph Responsive ◽  
Alkaline Conditions ◽  
Maize Kernels

ABSTRACT Fumonisins are a group of mycotoxins that contaminate maize and cause leukoencephalomalacia in equine, pulmonary edema in swine, and promote cancer in mice. Fumonisin biosynthesis in Fusarium verticillioides is repressed by nitrogen and alkaline pH. We cloned a PACC-like gene (PAC1) from F. verticillioides. PACC genes encode the major transcriptional regulators of several pH-responsive pathways in other filamentous fungi. In Northern blot analyses, a PAC1 probe hybridized to a 2.2-kb transcript present in F. verticillioides grown at alkaline pH. A mutant of F. verticillioides with a disrupted PAC1 gene had severely impaired growth at alkaline pH. The mutant produced more fumonisin than the wild type when grown on maize kernels and in a synthetic medium buffered at an acidic pH, 4.5. The mutant, but not the wild type, also produced fumonisin B1 when mycelia were resuspended in medium buffered at an alkaline pH, 8.4. Transcription of FUM1, a gene involved in fumonisin biosynthesis, was correlated with fumonisin production. We conclude that PAC1 is required for growth at alkaline pH and that Pac1 may have a role as a repressor of fumonisin biosynthesis under alkaline conditions.

Tumoral acidic pH-responsive MPEG-poly(β-amino ester) polymeric micelles for cancer targeting therapy

2010 ◽  
Vol 144 (2) ◽  
pp. 259-266 ◽  
Author(s):  
Kyung Hyun Min ◽  
Jong-Ho Kim ◽  
Sang Mun Bae ◽  
Hyeri Shin ◽  
Min Sang Kim ◽  
...  
Keyword(s):  
Polymeric Micelles ◽  
Cancer Targeting ◽  
Acidic Ph ◽  
Amino Ester ◽  
Ph Responsive ◽  
Targeting Therapy

scholarly journals Cytosolic protein delivery using pH-responsive, charge-reversible lipid nanoparticles

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yusuke Hirai ◽  
Hisaaki Hirose ◽  
Miki Imanishi ◽  
Tomohiro Asai ◽  
Shiroh Futaki
Keyword(s):  
Protein Delivery ◽  
Electrostatic Interactions ◽  
Fluorescent Protein ◽  
Lipid Nanoparticles ◽  
Endosomal Escape ◽  
Ph Responsive ◽  
Cargo Proteins ◽  
Green Fluorescent ◽  
Intracellular Protein Delivery ◽  
Endosomal Release

AbstractAlthough proteins have attractive features as biopharmaceuticals, the difficulty in delivering them into the cell interior limits their applicability. Lipid nanoparticles (LNPs) are a promising class of delivery vehicles. When designing a protein delivery system based on LNPs, the major challenges include: (i) formulation of LNPs with defined particle sizes and dispersity, (ii) efficient encapsulation of cargo proteins into LNPs, and (iii) effective cellular uptake and endosomal release into the cytosol. Dioleoylglycerophosphate-diethylenediamine (DOP-DEDA) is a pH-responsive, charge-reversible lipid. The aim of this study was to evaluate the applicability of DOP-DEDA-based LNPs for intracellular protein delivery. Considering the importance of electrostatic interactions in protein encapsulation into LNPs, a negatively charged green fluorescent protein (GFP) analog was successfully encapsulated into DOP-DEDA-based LNPs to yield diameters and polydispersity index of < 200 nm and < 0.2, respectively. Moreover, ~ 80% of the cargo proteins was encapsulated into the LNPs. Cytosolic distribution of fluorescent signals of the protein was observed for up to ~ 90% cells treated with the LNPs, indicating the facilitated endocytic uptake and endosomal escape of the cargo attained using the LNP system.

scholarly journals Dendritic Cell-Targeted pH-Responsive Extracellular Vesicles for Anticancer Vaccination

Pharmaceutics ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 54 ◽  
Author(s):  
Hyuk Lee ◽  
Hongsuk Park ◽  
Hyeong Yu ◽  
Kun Na ◽  
Kyung Oh ◽  
...  
Keyword(s):  
T Cells ◽  
Extracellular Vesicles ◽  
Cd8 T Cells ◽  
Lipid A ◽  
Endosomal Escape ◽  
Dependent Manner ◽  
Ph Responsive ◽  
Mucin 1 ◽  
Monophosphoryl Lipid A ◽  
Anticancer Vaccine

Immunotherapy can potentially treat cancers on a patient-dependent manner. Most of the efforts expended on anticancer vaccination parallel the efforts expended on prototypical immunization in infectious diseases. In this study, we designed and synthesized pH-responsive extracellular vesicles (EVs) coupled with hyaluronic acid (HA), 3-(diethylamino)propylamine (DEAP), monophosphoryl lipid A (MPLA), and mucin 1 peptide (MUC1), referred to as HDEA@EVAT. HDEA@EVAT potentiated the differentiation and maturation of monocytes into dendritic cells (DCs) and the priming of CD8+ T-cells for cancer therapy. MPLA and HA enabled HDEA@EVAT to interact with the toll-like receptor 4 and the CD44 receptor on DCs, followed by endosomal escape, owing to the protonation of pH-sensitive DEAP on the EV in conjunction with MUC1 release. The MUC1 was then processed and presented to DCs to activate CD8+ T-cells for additional anticancer-related immune reactions. Our findings support the anticancer vaccine activity by which HDEA@EVAT expedites the interaction between DCs and CD8+ T-cells by inducing DC-targeted maturation and by presenting the cancer-associated peptide MUC1.

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