High-Effective Gene Delivery Based on Cyclodextrins Multivalent Assembly in Target Cancer Cells

Author(s):  
Yao-Hua Liu ◽  
Yu Liu

Nucleic acids condensation and controlled release remain significant challenges of gene therapy in chemical biology and nanotechnology fields. In this work, we have reported a polysaccharide supramolecular assembly constructed by...

2020 ◽  
Vol 20 (11) ◽  
pp. 821-830
Author(s):  
Prasad Pofali ◽  
Adrita Mondal ◽  
Vaishali Londhe

Background: Current gene therapy vectors such as viral, non-viral, and bacterial vectors, which are used for cancer treatment, but there are certain safety concerns and stability issues of these conventional vectors. Exosomes are the vesicles of size 40-100 nm secreted from multivesicular bodies into the extracellular environment by most of the cell types in-vivo and in-vitro. As a natural nanocarrier, exosomes are immunologically inert, biocompatible, and can cross biological barriers like the blood-brain barrier, intestinal barrier, and placental barrier. Objective: This review focusses on the role of exosome as a carrier to efficiently deliver a gene for cancer treatment and diagnosis. The methods for loading of nucleic acids onto the exosomes, advantages of exosomes as a smart intercellular shuttle for gene delivery and therapeutic applications as a gene delivery vector for siRNA, miRNA and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and also the limitations of exosomes as a gene carrier are all reviewed in this article. Methods: Mostly, electroporation and chemical transfection are used to prepare gene loaded exosomes. Results: Exosome-mediated delivery is highly promising and advantageous in comparison to the current delivery methods for systemic gene therapy. Targeted exosomes, loaded with therapeutic nucleic acids, can efficiently promote the reduction of tumor proliferation without any adverse effects. Conclusion: In the near future, exosomes can become an efficient gene carrier for delivery and a biomarker for the diagnosis and treatment of cancer.


Nanoscale ◽  
2020 ◽  
Vol 12 (18) ◽  
pp. 10189-10195 ◽  
Author(s):  
Xin Zhao ◽  
Dongyang Tang ◽  
Ying Wu ◽  
Shaoqing Chen ◽  
Cheng Wang

The artifical cell system for the gene therapy of cancer might be a promising approach for the reversal of neoplastic progress of cancer cells.


2021 ◽  
Author(s):  
Moataz Dowaidar

Nucleic acid-based therapeutics such as siRNA and miRNA employ the silencing capabilities of the RNAi mechanism to affect the expression of one gene or several genes in target cells. Nucleic acid-based therapies enable accurate, targeted administration and overcoming drug resistance in diverse cancer cells. Several studies have shown that they can be utilized alongside pharmacological therapy to increase the efficacy of existing therapies. In addition, nucleic acid-based therapies have the potential to widen the spectrum of druggable targets for a range of diseases and emerge as a novel therapeutic technique for treating a number of diseases that are today untreatable. Nucleic acids are dependent on their effective distribution to target cells, which need correct complexation and encapsulation in a delivery mechanism. Although nucleic acids exist in a variety of forms and sizes, their physical and chemical commonality allow them to be loaded into a wide range of delivery vehicles. The primary biomaterials used to encapsulate genetic components were cationic lipids and polymers. Furthermore, the experiments focused particularly on effective transfection in target cells.Recent breakthroughs in NP-based RNA therapeutics have spurred a flood of clinical research, facing many challenges. In vivo, pharmacokinetics of different RNA-based medications must be researched to establish the viability and therapeutic potential of nucleic acid-based therapeutics. The U.S. Food and Drug Administration recently authorized many NP-based gene therapy. In 2019, Novartis authorized Zolgensma (onasemnogene abeparvovec-xioi) to treat spinal muscle atrophy. The first clinical research employing siRNA began in 2004 and is considered a milestone in nucleic acid-based drug development. Thirty clinical investigations have subsequently been completed. In 2018, the US FDA cleared Onpattro (Patisiran, Alnylam Pharmaceuticals) for the treatment of polyneuropathy caused by transthyretin amyloidosis.Several new generations of nucleic acid compositions employing polymer nanoparticles or liposomes are presently undergoing clinical testing. If allowed, the debut of nucleic acid-based treatments would represent a watershed event in immunotherapy. Advances in the design and development of biocompatible nanomaterials would allow us to overcome the above-mentioned problems and so show the potential to deliver nucleic acids in the treatment of a number of illnesses.


2020 ◽  
Vol 21 (21) ◽  
pp. 7867
Author(s):  
Effrosyni Tsafa ◽  
Kaoutar Bentayebi ◽  
Supachai Topanurak ◽  
Teerapong Yata ◽  
Justyna Przystal ◽  
...  

Merging targeted systemic gene delivery and systemic chemotherapy against cancer, chemovirotherapy, has the potential to improve chemotherapy and gene therapy treatments and overcome cancer resistance. We introduced a bacteriophage (phage) vector, named human adeno-associated virus (AAV)/phage or AAVP, for the systemic targeting of therapeutic genes to cancer. The vector was designed as a hybrid between a recombinant adeno-associated virus genome (rAAV) and a filamentous phage capsid. To achieve tumor targeting, we displayed on the phage capsid the double-cyclic CDCRGDCFC (RGD4C) ligand that binds the alpha-V/beta-3 (αvβ3) integrin receptor. Here, we investigated a combination of doxorubicin chemotherapeutic drug and targeted gene delivery by the RGD4C/AAVP vector. Firstly, we showed that doxorubicin boosts transgene expression from the RGD4C/AAVP in two-dimensional (2D) cell cultures and three-dimensional (3D) tumor spheres established from human and murine cancer cells, while preserving selective gene delivery by RGD4C/AAVP. Next, we confirmed that doxorubicin does not increase vector attachment to cancer cells nor vector cell entry. In contrast, doxorubicin may alter the intracellular trafficking of the vector by facilitating nuclear accumulation of the RGD4C/AAVP genome through destabilization of the nuclear membrane. Finally, a combination of doxorubicin and RGD4C/AAVP-targeted suicide gene therapy exerts a synergistic effect to destroy human and murine tumor cells in 2D and 3D tumor sphere settings.


2016 ◽  
Vol 14 (28) ◽  
pp. 6857-6870 ◽  
Author(s):  
Mallikarjun Gosangi ◽  
Thasneem Yoosuf Mujahid ◽  
Vijaya Gopal ◽  
Srilakshmi V. Patri

Gene therapy, a promising strategy for the delivery of therapeutic nucleic acids, is greatly dependent on the development of efficient vectors.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 920
Author(s):  
Pavel A. Puchkov ◽  
Michael A. Maslov

Gene therapy requires an effective and safe delivery vehicle for nucleic acids. In the case of non-viral vehicles, including cationic liposomes, the structure of compounds composing them determines the efficiency a lot. Currently, cationic amphiphiles are the most frequently used compounds in liposomal formulations. In their structure, which is a combination of hydrophobic and cationic domains and includes spacer groups, each component contributes to the resulting delivery efficiency. This review focuses on polycationic and disulfide amphiphiles as prospective cationic amphiphiles for gene therapy and includes a discussion of the mutual influence of structural components.


2016 ◽  
Vol 33 (5) ◽  
pp. 648-654 ◽  
Author(s):  
Hideaki Kakeya

This highlight focuses on our recent discoveries and chemical genetics approaches for bioactive microbial metabolites that target cancer cells, the cancer microenvironment, and cell membrane signalling. In addition, the development of two new platforms to identify the cellular targets of these molecules is also discussed.


2018 ◽  
Vol 33 (2) ◽  
pp. 216-226 ◽  
Author(s):  
Tuck-Yun Cheang ◽  
Yi-Yan Lei ◽  
Zhan-Qiang Zhang ◽  
Hong-Yan Zhou ◽  
Run-Yi Ye ◽  
...  

Gene therapy with herpes simplex virus thymidine kinase gene (HSV-TK), which is also known as “suicide” gene therapy, is effective in various tumor models. The lack of a safe and efficient gene delivery system has become a major obstacle to “suicide” gene therapy. In this study, the cytotoxicity and transfection efficiency of graphene oxide–hydroxyapatite (GO–Hap) were analyzed by MTS and flow cytometry, respectively. A series of assays were performed to evaluate the effects of GO–HAp/p-HRE/ERE-Sur-TK combined with ganciclovir treatment on growth of human breast normal and cancer cells. The results showed that GO–HAp nanocomposites effectively transfected cells with minimum toxicity. GO–HAp/p-HRE/ERE-Sur-TK combined with ganciclovir treatment inhibited the proliferation and induced cell apoptosis in cancer cells, while the cytotoxic effects are tolerable in normal breast cells. We conclude that the GO–HAp nanocomposites have significant potential as a gene delivery vector for cancer therapy.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 446
Author(s):  
Henrique Faneca

The advances in the field of gene therapy have significantly improved the possibility for nucleic acids as highly promising agents for the treatment of both inherited and acquired human diseases [...]


2017 ◽  
Vol 5 (34) ◽  
pp. 7194-7203 ◽  
Author(s):  
Yilun Wu ◽  
Wenyi Gu ◽  
Jie Tang ◽  
Zhi Ping Xu

New hybrid nanoparticles can efficiently deliver dsDNA/siRNA to cancer cells, with the gene release precisely controlled in the endosomal pH range.


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