Enhanced nuclear gene delivery via integrating and streamlining intracellular pathway

Qi, Lian-Yu; Wang, Yi; Hu, Li-Fan; Zhao, Pu-Song; Yu, Hao-Yuan; Liu, Xing; Gao, Xiangdong; Cao, Qing-Ri; Jiang, Hu‐Lin

doi:10.1016/j.jconrel.2021.11.046

Cited by 14 publications

(8 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results showed that the introduction of extracted mitochondria changed the multiple pathways mediated endocytosis of Lipo@Cy5-mRNA to the macropinocytosis of ML@Cy5-mRNA (Supplementary Fig. 4e), which was bene cial for increasing the cellular uptake of genes by decreasing endosomal degradation 33,34 . More importantly, we detected Parkin protein expression and found that the cells treated with MLPers expressed more Parkin protein than those of the other groups.…”

Section: Resultsmentioning

confidence: 99%

Suppression of mitochondrial heterogeneity via engineered mitochondria for reversion of mitochondrial disease-related phenotypes

Wang

Liu

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Mitochondrial heterogeneity above the biochemical threshold (~50% damaged mitochondria load) induces the symptom manifest of multiple mitochondrial diseases without effective treatment. However, current mitochondria-targeted therapies related to mitochondrial heterogeneity regulation have yielded unsatisfactory clinical incomes due to the risk of damaged mitochondria carryover and the imbalance of mitochondrial homeostasis. Here, we show that engineered mitochondria (Mitochondria-Lipo@mParkin, MLPers) constructed by adhesion of mitophagy-mediated liposomes to the surface of exogenous mitochondria can supply healthy mitochondria via exogenous mitochondria and both remove damaged mitochondria via enhanced mitophagy. MLPers decrease the high level of mitochondrial heterogeneity to less than 30% which is obviously lower than their biochemical threshold, and lead to the reversion of disease-related phenotypes in two mouse models of tricky mitochondrial diseases (Leber’s hereditary optic neuropathy and idiopathic pulmonary fibrosis). The surface adhesion-engineered mitochondria are powerful tools for maintaining homeostasis of mitochondrial pool and offer a translational approach for pan-mitochondrial disease therapies.

show abstract

Section: Resultsmentioning

confidence: 99%

Suppression of mitochondrial heterogeneity via engineered mitochondria for reversion of mitochondrial disease-related phenotypes

Wang

Liu

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Indeed, it is known that the disulfide chemical bond (S-S) is sensitive to reducing environments. When molecules containing this bond are close to reducing species, they undergo cleavage [ 207 ]. On the other hand, GO offers a large surface area that is capable of assembling numerous molecules containing disulfide groups and that respond to the tumor environment for controlled payload release.…”

Section: Controlled Release Strategiesmentioning

confidence: 99%

“…Such a system was used to load and transport pDNA, as it can form electrostatic interactions with the positively charged amine groups of the polymer chains. The ability to release the gene via disulfide bond degradation once internalized into tumor cells was preliminarily verified by incubation in DTT (i.e., a small molecule antioxidant) in order to simulate the intracellular reducing environment [ 207 ]. The results showed that after treatment in DTT, the disulfide bonds between the polymer chains and GO were broken, resulting in the release of pDNA.…”

Section: Controlled Release Strategiesmentioning

confidence: 99%

“…Other studies in the literature have exploited this mechanism to control the payload release, but most of them have focused on drug transport [ 186 , 208 ] or have used different nanoparticles [ 207 , 209 ]. Nevertheless, there is evidence that once the GO is functionalized by molecules containing disulfide bonds, oligonucleotide chains can also be loaded onto such systems.…”

Section: Controlled Release Strategiesmentioning

confidence: 99%

See 1 more Smart Citation

Characteristics of Graphene Oxide for Gene Transfection and Controlled Release in Breast Cancer Cells

Grilli

Gohari

Zou

2022

IJMS

View full text Add to dashboard Cite

Functionalized graphene oxide (GO) nanoparticles are being increasingly employed for designing modern drug delivery systems because of their high degree of functionalization, high surface area with exceptional loading capacity, and tunable dimensions. With intelligent controlled release and gene silencing capability, GO is an effective nanocarrier that permits the targeted delivery of small drug molecules, antibodies, nucleic acids, and peptides to the liquid or solid tumor sites. However, the toxicity and biocompatibility of GO-based formulations should be evaluated, as these nanomaterials may introduce aggregations or may accumulate in normal tissues while targeting tumors or malignant cells. These side effects may potentially be impacted by the dosage, exposure time, flake size, shape, functional groups, and surface charges. In this review, the strategies to deliver the nucleic acid via the functionalization of GO flakes are summarized to describe the specific targeting of liquid and solid breast tumors. In addition, we describe the current approaches aimed at optimizing the controlled release towards a reduction in GO accumulation in non-specific tissues in terms of the cytotoxicity while maximizing the drug efficacy. Finally, the challenges and future research perspectives are briefly discussed.

show abstract

“…The passive methods for naked gene transfer have the advantages of having no external energy supply and simple equipment, but the vector, especially the virus vector, has limitations and safety defects. For example, retroviruses with viral vectors have the potential risks of replication ability, insertion mutation, and activation of oncogenes; adenoviruses have the side effects and potential risks of causing immune responses [ 5 ]. However, the application of viral vectors is greatly limited due to limited DNA loading, difficult vector assembly, low efficiency of in vivo introduction, and high costs.…”

Section: Introductionmentioning

confidence: 99%

A Microfluidic System of Gene Transfer by Ultrasound

et al. 2022

View full text Add to dashboard Cite

Ultrasonic gene transfer has advantages beyond other cell transfer techniques because ultrasound does not directly act on cells, but rather pushes the gene fragments around the cells into cells through an acoustic hole effect. Most examples reported were carried out in macro volumes with conventional ultrasonic equipment. In the present study, a MEMS focused ultrasonic transducer based on piezoelectric thin film with flexible substrate was integrated with microchannels to form a microfluidic system of gene transfer. The core part of the system is a bowl-shaped curved piezoelectric film structure that functions to focus ultrasonic waves automatically. Therefore, the low input voltage and power can obtain the sound pressure exceeding the cavitation threshold in the local area of the microchannel in order to reduce the damage to cells. The feasibility of the system is demonstrated by finite element simulation and an integrated system of MEMS ultrasonic devices and microchannels are developed to successfully carry out the ultrasonic gene transfection experiments for HeLa cells. The results show that having more ultrasonic transducers leads a higher transfection rate. The system is of great significance to the development of single-cell biochip platforms for early cancer diagnosis and assessment of cancer treatment.

show abstract

Enhanced nuclear gene delivery via integrating and streamlining intracellular pathway

Cited by 14 publications

References 42 publications

Suppression of mitochondrial heterogeneity via engineered mitochondria for reversion of mitochondrial disease-related phenotypes

Suppression of mitochondrial heterogeneity via engineered mitochondria for reversion of mitochondrial disease-related phenotypes

Characteristics of Graphene Oxide for Gene Transfection and Controlled Release in Breast Cancer Cells

A Microfluidic System of Gene Transfer by Ultrasound

Contact Info

Product

Resources

About