Protein liposomes-mediated targeted acetylcholinesterase gene delivery for effective liver cancer therapy

Abstract Background Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. Proteolipid integrated with tumor-targeting potential of functional protein and excellent gene delivery performance has shown potential for targeted gene therapy. Results Herein, we prepared transferrin-modified liposomes (Tf-PL) for the targeted delivery of acetylcholinesterase (AChE) therapeutic gene to liver cancer. We found that the derived Tf-PL/AChE liposomes exhibited much higher transfection efficiency than the commercial product Lipo 2000 and shown premium targeting efficacy to liver cancer SMMC-7721 cells in vitro. In vivo, the Tf-PL/AChE could effectively target liver cancer, and significantly inhibit the growth of liver cancer xenografts grafted in nude mice by subcutaneous administration. Conclusions This study proposed a transferrin-modified proteolipid-mediated gene delivery strategy for targeted liver cancer treatment, which has a promising potential for precise personalized cancer therapy.

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Protein Liposomes-Mediated Targeted Acetylcholinesterase Gene Delivery for Effective Liver Cancer Therapy

10.21203/rs.3.rs-45975/v3 ◽

2021 ◽

Author(s):

Kai Wang ◽

Fusheng Shang ◽

Dagui Chen ◽

Tieliu Cao ◽

Xiaowei Wang ◽

...

Keyword(s):

Gene Therapy ◽

Cancer Therapy ◽

Gene Delivery ◽

Liver Cancer ◽

Targeted Delivery ◽

Tumor Targeting ◽

Transfection Efficiency ◽

Subcutaneous Administration ◽

Viral Gene ◽

Functional Protein

Abstract Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. Proteolipid integrated with tumor-targeting potential of functional protein and excellent gene delivery performance has shown potential for targeted gene therapy.Results: Herein, we prepared transferrin-modified liposomes (Tf-PL) for the targeted delivery of acetylcholinesterase (AChE) therapeutic gene to liver cancer. We found that the derived Tf-PL/AChE liposomes exhibited much higher transfection efficiency than the commercial product Lipo 2000 and shown premium targeting efficacy to liver cancer SMMC-7721 cells in vitro. In vivo, the Tf-PL/AChE could effectively target liver cancer, and significantly inhibit the growth of liver cancer xenografts grafted in nude mice by subcutaneous administration. Conclusion: This study proposed a transferrin-modified proteolipid-mediated gene delivery strategy for targeted liver cancer treatment, which has a promising potential for precise personalized cancer therapy.

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Targeted Protein Liposomes-Mediated AChE Gene Therapy for Effective Liver Cancer Treatment

10.21203/rs.3.rs-45975/v2 ◽

2020 ◽

Author(s):

Kai Wang ◽

Fusheng Shang ◽

Dagui Chen ◽

Tieliu Cao ◽

Xiaowei Wang ◽

...

Keyword(s):

Gene Therapy ◽

Cancer Therapy ◽

Gene Delivery ◽

Liver Cancer ◽

Cancer Treatment ◽

Targeted Delivery ◽

Tumor Targeting ◽

Transfection Efficiency ◽

Subcutaneous Administration ◽

Viral Gene

Abstract Background: Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. Proteolipid integrated with tumor-targeting potential of functional protein and excellent gene delivery performance has shown potential for targeted gene therapy.Results: Herein, we prepared transferrin-modified liposomes (Tf-PL) for the targeted delivery of acetylcholinesterase (AChE) therapeutic gene to liver cancer. We found that the derived Tf-PL/AChE liposomes exhibited much higher transfection efficiency than the commercial product Lipo 2000 and shown premium targeting efficacy to liver cancer SMMC-7721 cells in vitro. In vivo, the Tf-PL/AChE could effectively target liver cancer, and significantly inhibit the growth of liver cancer xenografts grafted in nude mice by subcutaneous administration. Conclusion: This study proposed a transferrin-modified proteolipid-mediated gene delivery strategy for targeted liver cancer treatment, which has a promising potential for precise personalized cancer therapy.

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Long-Circulating Polymeric Nanovectors for Tumor-Selective Gene Delivery

Technology in Cancer Research & Treatment ◽

10.1177/153303460500400605 ◽

2005 ◽

Vol 4 (6) ◽

pp. 615-625 ◽

Cited By ~ 71

Author(s):

Sushma Kommareddy ◽

Sandip B. Tiwari ◽

Mansoor M. Amiji

Keyword(s):

Gene Therapy ◽

Gene Delivery ◽

Viral Vectors ◽

High Efficiency ◽

Transfection Efficiency ◽

The United States ◽

Medical Intervention ◽

Hydrophilic Polymers ◽

Circulation Time ◽

Viral Gene

Significant advances in the understanding of the genetic abnormalities that lead to the development, progression, and metastasis of neoplastic diseases has raised the promise of gene therapy as an approach to medical intervention. Most of the clinical protocols that have been approved in the United States for gene therapy have used the viral vectors because of the high efficiency of gene transfer. Conventional means of gene delivery using viral vectors, however, has undesirable side effects such as insertion of mutational viral gene into the host genome and development of replication competent viruses. Among non-viral gene delivery methods, polymeric nanoparticles are increasingly becoming popular as vectors of choice. The major limitation of these nanoparticles is poor transfection efficiency at the target site after systemic administration due to uptake by the cells of reticuloendothelial system (RES). In order to reduce the uptake by the cells of the RES and improve blood circulation time, these nanoparticles are coated with hydrophilic polymers such as poly(ethylene glycol) (PEG). This article reviews the use of such hydrophilic polymers employed for improving the circulation time of the nanocarriers. The mechanism of polymer coating and factors affecting the circulation time of these nanocarriers will be discussed. In addition to the long circulating property, modifications to improve the target specificity of the particles and the limitations of steric protection will be analyzed.

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Non-viral Gene Therapy for Osteoarthritis

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2020.618399 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ilona Uzieliene ◽

Ursule Kalvaityte ◽

Eiva Bernotiene ◽

Ali Mobasheri

Keyword(s):

Gene Therapy ◽

Gene Delivery ◽

Articular Chondrocytes ◽

Transfection Efficiency ◽

Viral Gene ◽

Synovial Joint ◽

Advantages And Disadvantages ◽

Viral Gene Therapy ◽

Viral Gene Delivery ◽

Significant Effort

Strategies for delivering nucleic acids into damaged and diseased tissues have been divided into two major areas: viral and non-viral gene therapy. In this mini-review article we discuss the application of gene therapy for the treatment of osteoarthritis (OA), one of the most common forms of arthritis. We focus primarily on non-viral gene therapy and cell therapy. We briefly discuss the advantages and disadvantages of viral and non-viral gene therapy and review the nucleic acid transfer systems that have been used for gene delivery into articular chondrocytes in cartilage from the synovial joint. Although viral gene delivery has been more popular due to its reported efficiency, significant effort has gone into enhancing the transfection efficiency of non-viral delivery, making non-viral approaches promising tools for further application in basic, translational and clinical studies on OA. Non-viral gene delivery technologies have the potential to transform the future development of disease-modifying therapeutics for OA and related osteoarticular disorders. However, further research is needed to optimize transfection efficiency, longevity and duration of gene expression.

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Targeted Protein Liposomes-Mediated AChE Gene Therapy for Effective Liver Cancer Treatment

10.21203/rs.3.rs-45975/v1 ◽

2020 ◽

Author(s):

Kai Wang ◽

Fusheng Shang ◽

Dagui Chen ◽

Jianpeng Jiao ◽

Tieliu Cao ◽

...

Keyword(s):

Gene Therapy ◽

Liver Cancer ◽

Nude Mice ◽

Transfection Efficiency ◽

Tumor Therapy ◽

Viral Gene ◽

Therapeutic Gene ◽

Vector Systems

Abstract The development of highly efficient non-viral gene vector systems has very important application value in the field of cancer therapy. The high protein content of proteolipids allows for high biocompatibility, low immunogenicity, and surface modification of proteins to confer more targeted drug/gene function. For the first time, this study selected transferrin, which has hepatocellular carcinoma cell targeting function, with a liposome backbone material to construct transferrin liposome (Tf-PL), and load acetylcholinesterase (AChE) therapeutic gene for in vitro and in vivo functions evaluation. The results showed that the Tf-PL transfection efficiency was higher than that of commercial Lipo 2000, low cytotoxicity and targeted ability to liver cancer SMMC-7721 cells. After tail vein injection, Tf-PL/AChE can effectively target to liver cancer, significantly inhibiting the growth of liver cancer xenografts in nude mice, prolonging the survival time of tumor-bearing nude mice, and also does not cause significant systemic toxicities. Our study provides a strategy for proteolipids targeting the transferrin receptor to carry therapeutic gene therapy for tumors. This method has strong tumor affinity and can provide an effective vector selection for precise tumor therapy.

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Polymeric Nanoparticles in Gene Therapy: New Avenues of Design and Optimization for Delivery Applications

Polymers ◽

10.3390/polym11040745 ◽

2019 ◽

Vol 11 (4) ◽

pp. 745 ◽

Cited By ~ 41

Author(s):

Raj Rai ◽

Saniya Alwani ◽

Ildiko Badea

Keyword(s):

Gene Therapy ◽

Gene Delivery ◽

Targeted Delivery ◽

Polymeric Nanoparticles ◽

Genetic Material ◽

Delivery Systems ◽

Viral Gene ◽

Cationic Polymers ◽

Natural Polymers ◽

Viral Gene Delivery

The field of polymeric nanoparticles is quickly expanding and playing a pivotal role in a wide spectrum of areas ranging from electronics, photonics, conducting materials, and sensors to medicine, pollution control, and environmental technology. Among the applications of polymers in medicine, gene therapy has emerged as one of the most advanced, with the capability to tackle disorders from the modern era. However, there are several barriers associated with the delivery of genes in the living system that need to be mitigated by polymer engineering. One of the most crucial challenges is the effectiveness of the delivery vehicle or vector. In last few decades, non-viral delivery systems have gained attention because of their low toxicity, potential for targeted delivery, long-term stability, lack of immunogenicity, and relatively low production cost. In 1987, Felgner et al. used the cationic lipid based non-viral gene delivery system for the very first time. This breakthrough opened the opportunity for other non-viral vectors, such as polymers. Cationic polymers have emerged as promising candidates for non-viral gene delivery systems because of their facile synthesis and flexible properties. These polymers can be conjugated with genetic material via electrostatic attraction at physiological pH, thereby facilitating gene delivery. Many factors influence the gene transfection efficiency of cationic polymers, including their structure, molecular weight, and surface charge. Outstanding representatives of polymers that have emerged over the last decade to be used in gene therapy are synthetic polymers such as poly(l-lysine), poly(l-ornithine), linear and branched polyethyleneimine, diethylaminoethyl-dextran, poly(amidoamine) dendrimers, and poly(dimethylaminoethyl methacrylate). Natural polymers, such as chitosan, dextran, gelatin, pullulan, and synthetic analogs, with sophisticated features like guanidinylated bio-reducible polymers were also explored. This review outlines the introduction of polymers in medicine, discusses the methods of polymer synthesis, addressing top down and bottom up techniques. Evaluation of functionalization strategies for therapeutic and formulation stability are also highlighted. The overview of the properties, challenges, and functionalization approaches and, finally, the applications of the polymeric delivery systems in gene therapy marks this review as a unique one-stop summary of developments in this field.

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Zn-promoted gene transfection efficiency for non-viral vectors: a mechanism study

New Journal of Chemistry ◽

10.1039/d1nj02115j ◽

2021 ◽

Author(s):

Xiao-Qi Yu ◽

Rui-Mo Zhao ◽

Yu Guo ◽

Hui-Zhen Yang ◽

Ji Zhang

Keyword(s):

Gene Therapy ◽

Nucleic Acid ◽

Gene Delivery ◽

Viral Vectors ◽

Transfection Efficiency ◽

Gene Transfection ◽

Viral Gene ◽

Mechanism Study ◽

High Affinity ◽

Gene Vectors

The development of cationic non-viral gene vectors that may overcome the obstacles in gene delivery is of great significance to gene therapy. Metallic complexes with high affinity to nucleic acid...

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Pegylated immuno-lipopolyplexes: A novel non-viral gene delivery system for liver cancer therapy

Journal of Controlled Release ◽

10.1016/j.jconrel.2010.02.005 ◽

2010 ◽

Vol 144 (1) ◽

pp. 75-81 ◽

Cited By ~ 35

Author(s):

Yurong Hu ◽

Kun Li ◽

Lei Wang ◽

Shasha Yin ◽

Zhenzhong Zhang ◽

...

Keyword(s):

Cancer Therapy ◽

Gene Delivery ◽

Liver Cancer ◽

Delivery System ◽

Viral Gene ◽

Gene Delivery System ◽

Viral Gene Delivery

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Stepwise Development of Biomimetic Chimeric Peptides for Gene Delivery

Protein and Peptide Letters ◽

10.2174/0929866527666200206153328 ◽

2020 ◽

Vol 27 (8) ◽

pp. 698-710

Author(s):

Roya Cheraghi ◽

Mahboobeh Nazari ◽

Mohsen Alipour ◽

Saman Hosseinkhani

Keyword(s):

Gene Delivery ◽

Targeted Delivery ◽

Viral Vectors ◽

Large Scale ◽

Transfection Efficiency ◽

Cationic Lipids ◽

Target Cells ◽

Scale Production ◽

Stepwise Development ◽

Chimeric Peptides

Gene-based therapy largely relies on the vector type that allows a selective and efficient transfection into the target cells with maximum efficacy and minimal toxicity. Although, genes delivered utilizing modified viruses transfect efficiently and precisely, these vectors can cause severe immunological responses and are potentially carcinogenic. A promising method of overcoming this limitation is the use of non-viral vectors, including cationic lipids, polymers, dendrimers, and peptides, which offer potential routes for compacting DNA for targeted delivery. Although non-viral vectors exhibit reduced transfection efficiency compared to their viral counterpart, their superior biocompatibility, non-immunogenicity and potential for large-scale production make them increasingly attractive for modern therapy. There has been a great deal of interest in the development of biomimetic chimeric peptides. Biomimetic chimeric peptides contain different motifs for gene translocation into the nucleus of the desired cells. They have motifs for gene targeting into the desired cell, condense DNA into nanosize particles, translocate the gene into the nucleus and enhance the release of the particle into the cytoplasm. These carriers were developed in recent years. This review highlights the stepwise development of the biomimetic chimeric peptides currently being used in gene delivery.

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