Application of Non-Viral Vectors in Drug Delivery and Gene Therapy

Ren, Shuaikai; Wang, Mengjie; Wang, Chunxin; Wang, Yan; Sun, Changjiao; Zeng, Zhanghua; Cui, Haixin; Zhao, Xiang

doi:10.3390/polym13193307

Cited by 24 publications

(14 citation statements)

References 296 publications

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“…To achieve site-specific delivery of the drug, targeting ligands such as immunoglobulins and their fragments are frequently attached to the liposomal surface for targeted delivery without affecting their integrity. To deliver non-viral vectors to endothelial surface receptors, immunoliposomes have been developed [ 196 ]. Non-viral systems such as cell-penetrating peptides can be considered as a feasible option to overcome the low membrane permeability of these charged macromolecules [ 197 ].…”

Section: Nanocarriers In Ocular Drug Deliverymentioning

confidence: 99%

Lipid Nanoparticles as a Promising Drug Delivery Carrier for Topical Ocular Therapy—An Overview on Recent Advances

et al. 2022

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Due to complicated anatomical and physical properties, targeted drug delivery to ocular tissues continues to be a key challenge for formulation scientists. Various attempts are currently being made to improve the in vivo performance of therapeutic molecules by encapsulating them in various nanocarrier systems or devices and administering them via invasive/non-invasive or minimally invasive drug administration methods. Biocompatible and biodegradable lipid nanoparticles have emerged as a potential alternative to conventional ocular drug delivery systems to overcome various ocular barriers. Lipid-based nanocarrier systems led to major technological advancements and therapeutic advantages during the last few decades of ocular therapy, such as high precorneal residence time, sustained drug release profile, minimum dosing frequency, decreased drug toxicity, targeted site delivery, and, therefore, an improvement in ocular bioavailability. In addition, such formulations can be given as fine dispersion in patient-friendly droppable preparation without causing blurred vision and ocular sensitivity reactions. The unique advantages of lipid nanoparticles, namely, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, and liposomes in intraocular targeted administration of various therapeutic drugs are extensively discussed. Ongoing and completed clinical trials of various liposome-based formulations and various characterization techniques designed for nanoemulsion in ocular delivery are tabulated. This review also describes diverse solid lipid nanoparticle preparation methods, procedures, advantages, and limitations. Functionalization approaches to overcome the drawbacks of lipid nanoparticles, as well as the exploration of new functional additives with the potential to improve the penetration of macromolecular pharmaceuticals, would quickly progress the challenging field of ocular drug delivery systems.

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Section: Nanocarriers In Ocular Drug Deliverymentioning

confidence: 99%

Lipid Nanoparticles as a Promising Drug Delivery Carrier for Topical Ocular Therapy—An Overview on Recent Advances

et al. 2022

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“…To date, more than 900,000 articles on the topic of gene therapy can be retrieved from the Web of Science; meanwhile, only around 3,180 gene therapy clinical trials have been approved, ongoing or completed worldwide, and 56.4% of these are in phase I 1 . Suitable vectors prevent naked nucleic acids introduced into the body from ubiquitous nucleases and renal elimination, and facilitate the process of targeted delivery and efficient internalization ( Ren et al, 2021 ). Nonviral carriers, especially nanoparticles, have demonstrated tremendous potential in the targeted delivery of genetic material in treating hereditary transthyretin amyloidosis, pancreatic cancer, and other diseases with lower immunogenicity, with larger loading capacity, and being free from unexpected gene integration when compared to viral vectors ( Ohno et al, 2013 ; Kamerkar et al, 2017 ; Adams et al, 2018 ; Yan et al, 2019 ; Cheng et al, 2020 ; Li et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Trends and Hotspots in Nanoparticles for the Targeted Delivery of Nucleic Acids: A Ten-Year Bibliometric Study

Huang

Zhan

et al. 2022

Front. Pharmacol.

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Nanoparticles for the gene therapy field have seen remarkable progress over the last 10 years; however, low delivery efficiency and other reasons impede the clinical translation of nanocarriers. Therefore, a summary of hotspots and trends in this field is needed to promote further research development. In this research, from 2011 to 2021, 1,221 full records and cited references of Web of Science–indexed manuscripts regarding nanoparticle-targeted delivery systems have been analyzed by CiteSpace, VOSviewer, and MapEquation. In these software, keywords co-occurrence networks, alluvial diagram, co-citation networks, and structural variation analysis were carried out to emphasize the scientific community’s focus on nanomedicine of targeted delivering of nucleic acids. Keywords such as transfection efficiency, tumor cell, membrane antigen, and siRNA delivery were highlighted in the density map from VOSviewer. In addition, an alluvial flow diagram was constructed to detect changes in concepts. In the co-citation network, cluster 1 (exosomes) and cluster 17 (genome editing) were new research fields, and the efforts in modifying nanoparticles were revealed in the structural variation analysis. Aptamer and SELEX (systematic evolution of ligands by exponential enrichment) represented a helpful system in targeted delivery. These results indicated that the transfection efficiency of nanocarriers required continuous improvements. With the approval of several nucleic acid drugs, a new content of nanoparticle carriers is to introduce gene-editing technology, especially CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR–associated protein 9). In addition, exosomes have great potential as targeted nanoparticles. By mapping the knowledge domains of nanomedicine in targeted delivering of nucleic acids, this study analyzed the intellectual structure of this domain in the recent 10 years, highlighting classical modifications on nanoparticles and estimating future trends for researchers and decision-makers interested in this field.

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“…The recurrence rate of high-grade gliomas (WHO grade III-IV) is as high as 95% within 2 years after initial resection ( Xiong et al, 2019 ). Drug or gene delivery vehicles commonly used to treat cancers, such as glioma include liposomes, nanoparticles, ionic polymers, microcapsules, and micropores ( Ren et al, 2021 ). However, the clinical therapeutic value of these vectors is limited by factors, such as low drug or gene load, poor stability, and low targeting efficiency ( Vikulina et al, 2019 ; Stephen et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

The inhibitory effect of human umbilical cord mesenchymal stem cells expressing anti-HAAH scFv-sTRAIL fusion protein on glioma

Xue

Wang

et al. 2022

Front. Bioeng. Biotechnol.

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Glioma is the most common malignant intracranial tumor with low 5-year survival rate. In this study, we constructed a plasmid expressing anti-HAAH single-chain antibody and sTRAIL fusion protein (scFv-sTRAIL), and explored the effects of the double gene modified human umbilical cord mesenchyreal stem cells (hucMSCs) on the growth of glioma in vitro and in vivo. The isolated hucMSCs were identified by detecting the adipogenic differentiation ability and the osteogenic differentiation ability. The phenotypes of hucMSCs were determined by the flow cytometry. The hucMSCs were infected with lentivirus expression scFv-sTRAIL fusion protein. The expression of sTRAIL in hucMSCs were detected by immunofluorescence staining, western blot and ELISA. The tropism of hucMSCs toward U87G cells was assessed by transwell assay. The inhibitory effect of hucMSCs on U87G cells were explored by CCK8 and apoptosis assay. The xenograft tumor was established by subcutaneously injection of U87G cells into the back of mice. The hucMSCs were injected via tail veins. The inhibitory effect of hucMSCs on glioma in vivo was assessed by TUNEL assay. The hucMSCs migrated into the xenograft tumor were revealed by detecting the green fluorescent. The results showed that the scFv-sTRAIL expression did not affect the phenotypes of hucMSCs. The scFv-sTRAIL expression promoted the tropism of hucMSCs toward U87G cells, enhanced the inhibitory effect and tumor killing effect of hucMSCs on U87G cells. The in vivo study showed that hucMSCs expressing scFv-sTRAIL demonstrated significantly higher inhibitory effect and tumor killing effect than hucMSCs expressing sTRAIL. The green fluorescence intensity in the mice injected with hucMSCs expressing scFv-sTRAIL was significantly higher than that injected with hucMSCs expressing sTRAIL. These data suggested that the scFv conferred the targeting effect of hucMSCs tropism towards the xenograft tumor. In conclusion, the hucMSCs expressing scFv-sTRAIL fusion protein gained the capability to target and kill gliomas cells in vitro and in vivo. These findings shed light on a potential therapy for glioma treatment.

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Application of Non-Viral Vectors in Drug Delivery and Gene Therapy

Cited by 24 publications

References 296 publications

Lipid Nanoparticles as a Promising Drug Delivery Carrier for Topical Ocular Therapy—An Overview on Recent Advances

Lipid Nanoparticles as a Promising Drug Delivery Carrier for Topical Ocular Therapy—An Overview on Recent Advances

Trends and Hotspots in Nanoparticles for the Targeted Delivery of Nucleic Acids: A Ten-Year Bibliometric Study

The inhibitory effect of human umbilical cord mesenchymal stem cells expressing anti-HAAH scFv-sTRAIL fusion protein on glioma

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