scholarly journals Improved In Vivo Delivery of Small RNA Based on the Calcium Phosphate Method

2021 ◽  
Vol 11 (11) ◽  
pp. 1160
Author(s):  
Xin Wu ◽  
Yuhki Yokoyama ◽  
Hidekazu Takahashi ◽  
Shihori Kouda ◽  
Hiroyuki Yamamoto ◽  
...  
Keyword(s):  
Small Rna ◽  
Liver Toxicity ◽  
Carbonate Apatite ◽  
Mouse Tumors ◽  
Tumor Delivery ◽  
Nanoparticle System ◽  
Ultrasonic Pulverization ◽  
Therapeutic Model ◽  
In Vivo Delivery

In the past few years, we have demonstrated the efficacy of a nanoparticle system, super carbonate apatite (sCA), for the in vivo delivery of siRNA/miRNA. Intravenous injection of sCA loaded with small RNAs results in safe, high tumor delivery in mouse models. To further improve the efficiency of tumor delivery and avoid liver toxicity, we successfully developed an inorganic nanoparticle device (iNaD) via high-frequency ultrasonic pulverization combined with PEG blending during the production of sCA. Compared to sCA loaded with 24 μg of miRNA, systemic administration of iNaD loaded with 0.75 μg of miRNA demonstrated similar delivery efficiency to mouse tumors with little accumulation in the liver. In the mouse therapeutic model, iNaD loaded with 3 μg of the tumor suppressor small RNA MIRTX resulted in an improved anti-tumor effect compared to sCA loaded with 24 μg. Our findings on the bio-distribution and therapeutic effect of iNaD provide new perspectives for future nanomedicine engineering.

scholarly journals Controlling DNA–nanoparticle serum interactions

2016 ◽  
Vol 113 (48) ◽  
pp. 13600-13605 ◽  
Author(s):  
Kyryl Zagorovsky ◽  
Leo Y. T. Chou ◽  
Warren C. W. Chan
Keyword(s):  
Contrast Agents ◽  
General Framework ◽  
Dye Molecules ◽  
Serum Stability ◽  
Nanoparticle Surface ◽  
Degradation Rates ◽  
Nanoparticle System ◽  
Dna Density ◽  
In Vivo Delivery

Understanding the interaction of molecularly assembled nanoparticles with physiological fluids is critical to their use for in vivo delivery of drugs and contrast agents. Here, we systematically investigated the factors and mechanisms that govern the degradation of DNA on the nanoparticle surface in serum. We discovered that a higher DNA density, shorter oligonucleotides, and thicker PEG layer increased protection of DNA against serum degradation. Oligonucleotides on the surface of nanoparticles were highly resistant to DNase I endonucleases, and degradation was carried out exclusively by protein-mediated exonuclease cleavage and full-strand desorption. These results enabled the programming of the degradation rates of the DNA-assembled nanoparticle system from 0.1 to 0.7 h−1and the engineering of superstructures that can release two different preloaded dye molecules with distinct kinetics and half-lives ranging from 3.3 to 9.8 h. This study provides a general framework for investigating the serum stability of DNA-containing nanostructures. The results advance our understanding of engineering principles for designing nanoparticle assemblies with controlled in vivo behavior and present a strategy for storage and multistage release of drugs and contrast agents that can facilitate the diagnosis and treatment of cancer and other diseases.

scholarly journals Defect structures of sodium and chloride co-substituted hydroxyapatite and its osseointegration capacity

2021 ◽  
Vol 56 (9) ◽  
pp. 5493-5508
Author(s):  
Dong Su Yoo ◽  
Jung Sang Cho ◽  
Yong-Chae Chung ◽  
Sang-Hoon Rhee
Keyword(s):  
Binding Energies ◽  
Dissolution Behavior ◽  
Total System ◽  
Carbonate Apatite ◽  
In Vivo Test ◽  
Co Substitution ◽  
Constituent Elements ◽  
Low Crystalline ◽  
Charged Point

AbstractA defect structure and osseointegration capacity of sodium and chloride co-substituted hydroxyapatite (NaClAp) were newly studied. The NaClAp was prepared by reacting H3PO4 and Ca(OH)2 with NaNO3 and NH4Cl followed by sintering; pure hydroxyapatite (HAp) was synthesized as a control. After sintering, the co-substitution of Ca and OH with Na and Cl, respectively, produced charged point defects at Ca and PO4 sites. Also, OH molecules partially adopted a head-on structure. The calculated total system energy of NaClAp was higher, whereas the binding energies between each constituent elements and system were lower than those of HAp. These results suggest that NaClAp was less stable than HAp, due to the formation of various defects by co-substitution of Na and Cl. Indeed, NaClAp exhibited higher dissolution behavior in simulated body fluid (SBF) compared with HAp. Accordingly, this increased the capability to produce low crystalline hydroxyl carbonate apatite, likely due to the increasing degree of apatite supersaturation in SBF. Besides, the NaClAp granules showed noticeable improvements in osseointegration capacity four weeks after in vivo test compared with HAp. Collectively, these results imply that the defects made by multiple ion substitutions are useful to increase osseointegration capacity of hydroxyapatite.

scholarly journals Adapting decarbonylation chemistry for the development of prodrugs capable of in-vivo delivery of carbon monoxide utilizing sweeteners as carrier molecules

2021 ◽  
Author(s):  
Ladie Kimberly De La Cruz ◽  
Xiaoxiao Yang ◽  
Anna Menshikh ◽  
Maya Brewer ◽  
Wen Lu ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Animal Models ◽  
Therapeutic Agent ◽  
Organ Injury ◽  
Signaling Molecule ◽  
In Vivo Delivery ◽  
Co Gas

Carbon monoxide as an endogenous signaling molecule exhibits pharmacological efficacy in various animal models of organ injury. To address the difficulty in using CO gas as a therapeutic agent for...

scholarly journals In Vitro and In Vivo Multispectral Photoacoustic Imaging for the Evaluation of Chromophore Concentration

Sensors ◽  
2021 ◽  
Vol 21 (10) ◽  
pp. 3366
Author(s):  
Aneline Dolet ◽  
Rita Ammanouil ◽  
Virginie Petrilli ◽  
Cédric Richard ◽  
Piero Tortoli ◽  
...  
Keyword(s):  
Remote Sensing ◽  
Photoacoustic Imaging ◽  
Hyperspectral Remote Sensing ◽  
Reference Spectrum ◽  
In Vivo Experiments ◽  
Mouse Tumors ◽  
Chromophore Concentration ◽  
Saturation Rate

Multispectral photoacoustic imaging is a powerful noninvasive medical imaging technique that provides access to functional information. In this study, a set of methods is proposed and validated, with experimental multispectral photoacoustic images used to estimate the concentration of chromophores. The unmixing techniques used in this paper consist of two steps: (1) automatic extraction of the reference spectrum of each pure chromophore; and (2) abundance calculation of each pure chromophore from the estimated reference spectra. The compared strategies bring positivity and sum-to-one constraints, from the hyperspectral remote sensing field to multispectral photoacoustic, to evaluate chromophore concentration. Particularly, the study extracts the endmembers and compares the algorithms from the hyperspectral remote sensing domain and a dedicated algorithm for segmentation of multispectral photoacoustic data to this end. First, these strategies are tested with dilution and mixing of chromophores on colored 4% agar phantom data. Then, some preliminary in vivo experiments are performed. These consist of estimations of the oxygen saturation rate (sO2) in mouse tumors. This article proposes then a proof-of-concept of the interest to bring hyperspectral remote sensing algorithms to multispectral photoacoustic imaging for the estimation of chromophore concentration.

PEGylated Carbon Nanocapsule: A Universal Reactor and Carrier for In Vivo Delivery of Hydrophobic and Hydrophilic Nanoparticles

2015 ◽  
Vol 8 (1) ◽  
pp. 350-362 ◽  
Author(s):  
Amritha Rammohan ◽  
Gargi Mishra ◽  
Binapani Mahaling ◽  
Lokesh Tayal ◽  
Ahana Mukhopadhyay ◽  
...  
Keyword(s):  
In Vivo Delivery
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