Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery

Author(s):  
John Hendershot ◽  
Adam E. Smith ◽  
Thomas A. Werfel

AMB Express ◽  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Bo Hu ◽  
Feng Gao ◽  
Chunbao Li ◽  
Boqing Zhang ◽  
Mingyang An ◽  
...  




2015 ◽  
Vol 220 ◽  
pp. 529-544 ◽  
Author(s):  
HongYan Zhu ◽  
ShengYu Zhang ◽  
Yong Ling ◽  
GuoLiang Meng ◽  
Yu Yang ◽  
...  


2008 ◽  
Vol 130 (11) ◽  
pp. 3272-3273 ◽  
Author(s):  
Martin Meyer ◽  
Alexander Philipp ◽  
Reza Oskuee ◽  
Claudia Schmidt ◽  
Ernst Wagner


2020 ◽  
Vol 2 (7) ◽  
pp. 2499-2503
Author(s):  
Marcel Klein-Hitpaß ◽  
Jan-Erik Ostwaldt ◽  
Carsten Schmuck ◽  
Michael Giese


Pharmaceutics ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 89 ◽  
Author(s):  
Md. Karim ◽  
Jayalaxmi Shetty ◽  
Rowshan Islam ◽  
Ahsanul Kaiser ◽  
Athirah Bakhtiar ◽  
...  

Inorganic nanoparticles hold great potential in the area of precision medicine, particularly for treating cancer owing to their unique physicochemical properties, biocompatibility and improved pharmacokinetics properties compared to their organic counterparts. Here we introduce strontium sulfite nanoparticles as new pH-responsive inorganic nanocarriers for efficient transport of siRNAs into breast cancer cells. We employed the simplest nanoprecipitation method to generate the strontium sulfite nanoparticles (SSNs) and demonstrated the dramatic roles of NaCl and d-glucose in particle growth stabilization in order to produce even smaller nanosize particles (Na-Glc-SSN) with high affinity towards negatively charged siRNA, enabling it to efficiently enter the cancer cells. Moreover, the nanoparticles were found to be degraded with a small drop in pH, suggesting their potential capability to undergo rapid dissolution at endosomal pH so as to release the payload. While these particles were found to be nontoxic to the cells, they showed higher potency in facilitating cancer cell death through intracellular delivery and release of oncogene-specific siRNAs targeting ros1 and egfr1 mRNA transcripts, than the strontium sulfite particles prepared in absence of NaCl and d-glucose, as confirmed by growth inhibition assay. The mouse plasma binding analysis by Q-TOF LC-MS/MS demonstrated less protein binding to smaller particles of Na-Glc-SSNs. The biodistribution studies of the particles after 4 h of treatment showed Na-Glc-SSNs had less off-target distribution than SSNs, and after 24 h, all siRNAs were cleared from all major organs except the tumors. ROS1 siRNA with its potential therapeutic role in treating 4T1-induced breast tumor was selected for subsequent in vivo tumor regression study, revealing that ROS1 siRNA-loaded SSNs exerted more significant anti-tumor effects than Na-Glc-SSNs carrying the same siRNA following intravenous administration, without any systemic toxicity. Thus, strontium sulfite emerged as a powerful siRNA delivery tool with potential applications in cancer gene therapy.



2019 ◽  
Vol 569 ◽  
pp. 118606 ◽  
Author(s):  
Mariko Sako ◽  
Furan Song ◽  
Ayaka Okamoto ◽  
Hiroyuki Koide ◽  
Takehisa Dewa ◽  
...  
Keyword(s):  


ACS Omega ◽  
2019 ◽  
Vol 4 (16) ◽  
pp. 16756-16767 ◽  
Author(s):  
Evan B. Glass ◽  
Shirin Masjedi ◽  
Stephanie O. Dudzinski ◽  
Andrew J. Wilson ◽  
Craig L. Duvall ◽  
...  


ACS Nano ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 187-197 ◽  
Author(s):  
Dominic W. Malcolm ◽  
Jomy J. Varghese ◽  
Janet E. Sorrells ◽  
Catherine E. Ovitt ◽  
Danielle S. W. Benoit


Author(s):  
Charu Tyagi

Gelatin-eudragit L100 nanoparticles of wet size range 170-563nm were prepared by two step dissolvation method and the effect of different concentrations of eudragit L100 and emulsifying agent - sodium lauryl sulphate (SLS) - on the particle size were studied. Synthesized nanoparticles were characterized by attenuated total reflectance-fourier transform infrared spectroscopy (ATRFTIR) and the mean size distribution. Insulin loading was done at a pH 7.4 and the in vitro insulin release studies of nanoparticles were carried out by simulating gastrointestinal tract condition which showed the minimal insulin release at pH 2.5 (20% in 90min) while appreciable release (40% in first 30min) at pH of 7.4. This pH responsive release pattern of the synthesized nanoparticles confers on the insulin protection from proteolytic degradation in acidic environment of stomach and upper intestinal part while enhancing bioavailability in the later part of intestine.



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