Nanotechnology-enabled gene delivery for cancer and other genetic diseases

Jiang, Tong; Gonzalez, Karina Marie; Cordova, Leyla Estrella; Lu, Jianqin

doi:10.1080/17425247.2023.2200246

Cited by 10 publications

(2 citation statements)

References 175 publications

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“…The human reticuloendothelial system, including the liver and spleen, can quickly identify and remove exogenous substances in the blood, ingest nanomaterials and accumulate the particles in the spleen and liver [18,20]. Kidney filtration also poses new challenges to the application of nanomaterials [22]. For instance, systemically administered nucleic acid drugs are easily excreted by the kidneys through glomerular filtration and Penetration is the key process for nanomaterials to cross the circulatory system to reach the target tissue for biological distribution [24].…”

Section: The Clinical Demand Development and Delivery Challenges Of N...mentioning

confidence: 99%

Research Progress on Nanomaterials for Tissue Engineering in Oral Diseases

Jiang,

Su,

et al. 2023

JFB

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Due to their superior antibacterial properties, biocompatibility and high conductivity, nanomaterials have shown a broad prospect in the biomedical field and have been widely used in the prevention and treatment of oral diseases. Also due to their small particle sizes and biodegradability, nanomaterials can provide solutions for tissue engineering, especially for oral tissue rehabilitation and regeneration. At present, research on nanomaterials in the field of dentistry focuses on the biological effects of various types of nanomaterials on different oral diseases and tissue engineering applications. In the current review, we have summarized the biological effects of nanoparticles on oral diseases, their potential action mechanisms and influencing factors. We have focused on the opportunities and challenges to various nanomaterial therapy strategies, with specific emphasis on overcoming the challenges through the development of biocompatible and smart nanomaterials. This review will provide references for potential clinical applications of novel nanomaterials in the field of oral medicine for the prevention, diagnosis and treatment of oral diseases.

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Section: The Clinical Demand Development and Delivery Challenges Of N...mentioning

confidence: 99%

Research Progress on Nanomaterials for Tissue Engineering in Oral Diseases

Jiang,

Su,

et al. 2023

JFB

Self Cite

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“…Cationic charges have been primarily used to stabilize the DNA through charge interaction in order to protect the plasmid DNA being delivered, even though the charge interaction with cell surface proteins was correlated to cell toxicity. [37][38][39][40] Recently, research has drifted away from large pDNA towards the use of siRNA and mRNA for their small size, high expression, and ability to knock down or lead to protein expression respectively without having to enter the nucleus; however, they also suffer from easy degradation during formulation and after administration, making their use difficult. While a drawback for pDNA was the requirement of nuclear localization it is recently being reconsidered.…”

Section: Introductionmentioning

confidence: 99%

Strategies for Improved pDNA Loading and Protection Using Cationic and Neutral LNPs with Industrial Scalability Potential Using Microfluidic Technology

Ottonelli,

Adani,

Bighinati

et al. 2024

IJN

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Purpose In recent years, microfluidic technologies have become mainstream in producing gene therapy nanomedicines (NMeds) following the Covid-19 vaccine; however, extensive optimizations are needed for each NMed type and genetic material. This article strives to improve LNPs for pDNA loading, protection, and delivery, while minimizing toxicity. Methods The microfluidic technique was optimized to form cationic or neutral LNPs to load pDNA. Classical “post-formulation” DNA addition vs “pre” addition in the aqueous phase were compared. All formulations were characterized (size, homogeneity, zeta potential, morphology, weight yield, and stability), then tested for loading efficiency, nuclease protection, toxicity, and cell uptake. Results Optimized LNPs formulated with DPPC: Chol:DOTAP 1:1:0.1 molar ratio and 10 µg of DOPE-Rhod, had a size of 160 nm and good homogeneity. The chemico-physical characteristics of cationic LNPs worsened when adding 15 µg/mL of pDNA with the “post” method, while maintaining their characteristics up to 100 µg/mL of pDNA with the “pre” addition remaining stable for 30 days. Interestingly, neutral LNPs formulated with the same method loaded up to 50% of the DNA. Both particles could protect the DNA from nucleases even after one month of storage, and low cell toxicity was found up to 40 µg/mL LNPs. Cell uptake occurred within 2 hours for both formulations with the DNA intact in the cytoplasm, outside of the lysosomes. Conclusion In this study, the upcoming microfluidic technique was applied to two strategies to generate pDNA-LNPs. Cationic LNPs could load 10x the amount of DNA as the classical approach, while neutral LNPs, which also loaded and protected DNA, showed lower toxicity and good DNA protection. This is a big step forward at minimizing doses and toxicity of LNP-based gene therapy.

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