Encapsulation of RNA by negatively charged human serum albumin via physical interactions

Wen, Hao; Yin, Yudan; Huang, Chao; Pan, Wei; Liang, Dehai

doi:10.1007/s11426-016-0094-8

Cited by 16 publications

(14 citation statements)

References 33 publications

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“…It may be noted that albumin and A-cRGD are negatively charged biopolymers and hence show poor interaction with the negatively charged siRNA (anionic phosphate side chain), which creates a repulsive environment for the encapsulation of anionic siRNA molecules. The poor biopolymer albumin–siRNA interaction can be ascribed to be the prime reason for poor siRNA encapsulation efficiency in the case of conventional albumin nanoplex, siANp. , The higher siRNA encapsulation in cases of DTsiANp and DTsiANp-cRGD can be ascribed to the adaption of a systematic dendrimer templated approach for siRNA encapsulation. It may be noted that the net anionic albumin/A-cRGD undergoes an effective interaction with the systematically designed cationic d :siR complex as compared to the anionic siRNA alone.…”

Section: Discussionmentioning

confidence: 99%

Cyclo-RGD Truncated Polymeric Nanoconstruct with Dendrimeric Templates for Targeted HDAC4 Gene Silencing in a Diabetic Nephropathy Mouse Model

et al. 2020

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Diabetic nephropathy (DN), a chronic progressive kidney disease, is a significant complication of diabetes mellitus. Dysregulation of the histone deacetylases (HDACs) gene has been implicated in the pathogenesis of DN. Hence, the HDAC-inhibitors have emerged as a critical class of therapeutic agents in DN; however, the currently available HDAC4-inhibitors are mostly nonselective in nature as well as inhibit multiple HDACs. RNA interference of HDAC4 (HDAC4 siRNA) has shown immense promise, but the clinical translation has been impeded due to lack of a targeted, specific, and in vivo applicable delivery modality. In the present investigation, we examined Cyclo(RGDfC) (cRGD) truncated polymeric nanoplex with dendrimeric templates for targeted HDAC4 Gene Silencing. The developed nanoplex exhibited enhanced encapsulation of siRNA and offered superior protection against serum RNase nucleases degradation. The nanoplex was tested on podocytes (in vitro), wherein it showed selective binding to the αvβ3 integrin receptor, active cellular uptake, and significant in vitro gene silencing. The in vivo experiments showed remarkable suppression of the HDAC4 and inhibition in the progression of renal fibrosis in the Streptozotocin (STZ) induced DN C57BL/6 mice model. Histopathological and toxicological studies revealed nonsignificant abnormality/toxicity with the nanoplex. Conclusively, nanoplex was found as a promising tactic for targeted therapy of podocytes and could be extended for other kidney-related ailments.

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Section: Discussionmentioning

confidence: 99%

Cyclo-RGD Truncated Polymeric Nanoconstruct with Dendrimeric Templates for Targeted HDAC4 Gene Silencing in a Diabetic Nephropathy Mouse Model

et al. 2020

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“…It may be noted that the conventional albumin-based siRNA delivery vector was found insufficient, incapable of encapsulating as well as effective homing of siRNA payload in the cytosolic compartment. This can be ascribed to the mismatch in their physiochemical attributes, wherein both being negatively charged 27 . At the same time, conventional albumin siRNA vector lacks the capability to avoid premature siRNA release in blood as well as mediate endo/lysosomal escape in the cellular compartment leading to its substantially reduced efficacy 22 .…”

Section: Discussionmentioning

confidence: 99%

“…However, the inherent architectural configuration of albumin is not adequate to guarantee a complete escape of the nanovector from the endo-lysosomal compartment as well as protect the loaded siRNA therapeutics from the harsh endo-lysosomal environment. Further, the anionic carboxylic side chain of albumin imparts limitation towards the encapsulation of anionic siRNA molecules (due to the existence of anionic phosphate side chain in siRNA architect) 26,27 .…”

Section: Introductionmentioning

confidence: 99%

Method and its Composition for encapsulation, stabilization, and delivery of siRNA in Anionic polymeric nanoplex: An In vitro- In vivo Assessment

Raval

Jogi

Gondaliya

et al. 2019

Sci Rep

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Small interfering RNA (siRNA) are synthetic RNA duplex designed to specifically knockdown the abnormal gene to treat a disease at cellular and molecular levels. In spite of their high potency, specificity, and therapeutic potential, the full-fledged utility of siRNA is predominantly limited to in vitro set-up. Till date, Onpattro is the only USFDA approved siRNA therapeutics available in the clinic. The lack of a reliable in vivo siRNA delivery carrier remains a foremost obstacle towards the clinical translation of siRNA therapeutics. To address the obstacles associated with siRNA delivery, we tested a dendrimer-templated polymeric approach involving a USFDA approved carrier (albumin) for in vitro as well as in vivo delivery of siRNA. The developed approach is simple in application, enhances the serum stability, avoids in vivo RNase-degradation and mediates cytosolic delivery of siRNA following the endosomal escape process. The successful in vitro and in vivo delivery of siRNA, as well as targeted gene knockdown potential, was demonstrated by HDAC4 inhibition in vitro diabetic nephropathy (DN) podocyte model as well as in vivo DN C57BL/6 mice model. The developed approach has been tested using HDAC4 siRNA as a model therapeutics, while the application can also be extended to other gene therapeutics including micro RNA (miRNA), plasmids oligonucleotides, etc.

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“…The data showed that HSA nanoparticles loaded with ONs were stable and had a narrow distribution of about 110 nm in diameter. Experiments with cells demonstrated that the empty nanocarriers showed high cellular uptake and no toxicity to Hela cells [ 91 ].…”

Section: Drug Delivery Systems For Onsmentioning

confidence: 99%

“…The load capacity, degradation rate and release kinetics of gelatin nanoparticles are adjustable, but natural gelatin nanoparticles are not useful as siRNA carriers [ 90 ]. However, it is easy to introduce specific ligands into gelatin nanoparticles [ 91 ] for targeting specific organs [ 89 ]. Gelatin can be easily modified with a number of functional groups and has shown low cytotoxicity and antigenicity.…”

Section: Drug Delivery Systems For Onsmentioning

confidence: 99%

Enhancing the Therapeutic Delivery of Oligonucleotides by Chemical Modification and Nanoparticle Encapsulation

Sun

Zhao

et al. 2017

Molecules

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Oligonucleotide (ON) drugs, including small interfering RNA (siRNA), microRNA (miRNA) and antisense oligonucleotides, are promising therapeutic agents. However, their low membrane permeability and sensitivity to nucleases present challenges to in vivo delivery. Chemical modifications of the ON offer a potential solution to improve the stability and efficacy of ON drugs. Combined with nanoparticle encapsulation, delivery at the site of action and gene silencing activity of chemically modified ON drugs can be further enhanced. In the present review, several types of ON drugs, selection of chemical modification, and nanoparticle-based delivery systems to deliver these ON drugs are discussed.

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Encapsulation of RNA by negatively charged human serum albumin via physical interactions

Cited by 16 publications

References 33 publications

Cyclo-RGD Truncated Polymeric Nanoconstruct with Dendrimeric Templates for Targeted HDAC4 Gene Silencing in a Diabetic Nephropathy Mouse Model

Cyclo-RGD Truncated Polymeric Nanoconstruct with Dendrimeric Templates for Targeted HDAC4 Gene Silencing in a Diabetic Nephropathy Mouse Model

Method and its Composition for encapsulation, stabilization, and delivery of siRNA in Anionic polymeric nanoplex: An In vitro- In vivo Assessment

Enhancing the Therapeutic Delivery of Oligonucleotides by Chemical Modification and Nanoparticle Encapsulation

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