scholarly journals A supramolecular platform for controlling and optimizing molecular architectures of siRNA targeted delivery vehicles

2020 ◽  
Vol 6 (31) ◽  
pp. eabc2148
Author(s):  
Yuting Wen ◽  
Hongzhen Bai ◽  
Jingling Zhu ◽  
Xia Song ◽  
Guping Tang ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Targeted Delivery ◽  
Tumor Therapy ◽  
Sirna Delivery ◽  
Targeted Gene Delivery ◽  
Delivery Vehicles ◽  
Molecular Architectures ◽  
Host Polymer

It requires multistep synthesis and conjugation processes to incorporate multifunctionalities into a polyplex gene vehicle to overcome numerous hurdles during gene delivery. Here, we describe a supramolecular platform to precisely control, screen, and optimize molecular architectures of siRNA targeted delivery vehicles, which is based on rationally designed host-guest complexation between a β-cyclodextrin–based cationic host polymer and a library of guest polymers with various PEG shape and size, and various density of ligands. The host polymer is responsible to load/unload siRNA, while the guest polymer is responsible to shield the vehicles from nonspecific cellular uptake, to prolong their circulation time, and to target tumor cells. A series of precisely controlled molecular architectures through a simple assembly process allow for a rapid optimization of siRNA delivery vehicles in vitro and in vivo for therapeutic siRNA-Bcl2 delivery and tumor therapy, indicating the platform is a powerful screening tool for targeted gene delivery vehicles.

scholarly journals Novel Mannan-PEG-PE Modified Bioadhesive PLGA Nanoparticles for Targeted Gene Delivery

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Guicun Wu ◽  
Fang Zhou ◽  
Linfu Ge ◽  
Ximin Liu ◽  
Fansheng Kong
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Polymeric Nanoparticles ◽  
Plga Nanoparticles ◽  
Gene Delivery System ◽  
Targeted Gene Delivery ◽  
Delivery Vehicles ◽  
Modification Rate

Purpose. Biodegradable polymeric nanoparticles have been used frequently as gene delivery vehicles. The aim of this study is to modify bioadhesive PLGA nanoparticles with novel synthetic mannan-PEG-PE (MN-PEG-PE) to obtain active targeted gene delivery system.Methods. Mannan-PEG-PE ligands were synthesized and modified onto the NPs/pEGFP complexes. The modification rate was optimized, and the characteristics of the vehicle were evaluated. Then, the modified vectors were intravenous delivered to rats, andin vivotargeting behavior of MN-PEG-PE modified PLGA nanoparticles/pEGFP complexes (MN-PEG-PE-NPs/pEGFP) in liver macrophages was investigated.Results. MN-PEG-PE-NPs/pEGFP displayed remarkably higher transfection efficiencies than nonmodified NPs/pEGFP bothin vitroandin vivo.Conclusions. Mannan containing targeting ligands could significantly improve the transfection efficiency of the carriers. MN-PEG-PE modified vectors very useful in targeted gene delivery.

Internal and External Triggering Mechanism of “Smart” Nanoparticle-Based DDSs in Targeted Tumor Therapy

2018 ◽  
Vol 24 (15) ◽  
pp. 1639-1651 ◽  
Author(s):  
Xian-ling Qian ◽  
Jun Li ◽  
Ran Wei ◽  
Hui Lin ◽  
Li-xia Xiong
Keyword(s):  
Targeted Delivery ◽  
Tumor Therapy ◽  
Burst Release ◽  
Tumor Site ◽  
Chemotherapeutic Drugs ◽  
Triggering Mechanism ◽  
Triggering Factors ◽  
Or Genes

Background: Anticancer chemotherapeutics have a lot of problems via conventional Drug Delivery Systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: “passive”, “active”, and “smart” targeting. Objective: To summarize the mechanisms of various internal and external “smart” stimulating factors on the basis of findings from in vivo and in vitro studies. Method: A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Results: Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), “smart” DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. Conclusion: In this review article, we summarize and classify the internal and external triggering mechanism of “smart” nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding.

scholarly journals Tumor-Targeting Peptides Search Strategy for the Delivery of Therapeutic and Diagnostic Molecules to Tumor Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 314
Author(s):  
Maria D. Dmitrieva ◽  
Anna A. Voitova ◽  
Maya A. Dymova ◽  
Vladimir A. Richter ◽  
Elena V. Kuligina
Keyword(s):  
Phage Display ◽  
Cell Sorting ◽  
Targeted Delivery ◽  
Tumor Targeting ◽  
Search Strategy ◽  
Tumor Therapy ◽  
Therapeutic Agents ◽  
Phage Libraries

Background: The combination of the unique properties of cancer cells makes it possible to find specific ligands that interact directly with the tumor, and to conduct targeted tumor therapy. Phage display is one of the most common methods for searching for specific ligands. Bacteriophages display peptides, and the peptides themselves can be used as targeting molecules for the delivery of diagnostic and therapeutic agents. Phage display can be performed both in vitro and in vivo. Moreover, it is possible to carry out the phage display on cells pre-enriched for a certain tumor marker, for example, CD44 and CD133. Methods: For this work we used several methods, such as phage display, sequencing, cell sorting, immunocytochemistry, phage titration. Results: We performed phage display using different screening systems (in vitro and in vivo), different phage libraries (Ph.D-7, Ph.D-12, Ph.D-C7C) on CD44+/CD133+ and without enrichment U-87 MG cells. The binding efficiency of bacteriophages displayed tumor-targeting peptides on U-87 MG cells was compared in vitro. We also conducted a comparative analysis in vivo of the specificity of the accumulation of selected bacteriophages in the tumor and in the control organs (liver, brain, kidney and lungs). Conclusions: The screening in vivo of linear phage peptide libraries for glioblastoma was the most effective strategy for obtaining tumor-targeting peptides providing targeted delivery of diagnostic and therapeutic agents to glioblastoma.

Receptor-Mediated Gene Delivery Using Chitosan Derivatives In Vitro and In Vivo

2007 ◽  
Vol 342-343 ◽  
pp. 449-452 ◽  
Author(s):  
Tae Hee Kim ◽  
Hua Jin ◽  
Hyun Woo Kim ◽  
Myung Haing Cho ◽  
Jae Woon Nah ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Delivery System ◽  
Transfection Efficiency ◽  
Viral Gene ◽  
Gene Delivery System ◽  
Targeted Gene Delivery ◽  
Cell Specificity ◽  
Selective Delivery

The key strategy for the advancement of gene therapy is the development of an efficient targeted gene delivery system into cells. The targeted gene delivery system is especially important in non-viral gene transfer which shows the relatively low transfection efficiency. It also opens the possibility of selective delivery of therapeutic plasmids to specific tissues. Chitosan has been considered to be a good candidate for gene delivery system, since it is already known as a biocompatible, biodegradable, and low toxic material with high cationic potential. However, low specificity and low transfection efficiency of chitosan need to be overcome prior to clinical trial. In this study, we focused on the chemical modification of chitosan for enhancement of cell specificity and transfection efficiency. Also, the potential of clinical application was investigated.

Receptor-Mediated Gene Delivery Using Chitosan Derivatives In Vitro and In Vivo

2007 ◽  
Vol 539-543 ◽  
pp. 641-646 ◽  
Author(s):  
Tae Hee Kim ◽  
Jin Hua ◽  
Hyun Woo Kim ◽  
Myung Haing Cho ◽  
Jae Woon Nah ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Delivery System ◽  
Transfection Efficiency ◽  
Viral Gene ◽  
Gene Delivery System ◽  
Targeted Gene Delivery ◽  
Cell Specificity ◽  
Selective Delivery

The development of an efficient targeted gene delivery system into cells is an important strategy for the advancement of gene therapy. The targeted gene delivery system is especially important in non-viral gene transfer which shows the relative low transfection efficiency. And it also opens the possibility of selective delivery of therapeutic plasmids to specific tissues. Chitosan has been considered to be a good candidate for gene delivery system, since it is already known as a biocompatible, biodegradable, and low toxic material with high cationic potential. However, low specificity and low transfection efficiency of chitosan need to be overcome prior to clinical trial. In this study, we focused on the chemical modification of chitosan for enhancement of cell specificity and transfection efficiency.

Lipid-Coated Gold Nanoparticles Functionalized by Folic Acid as Gene Vectors for Targeted Gene Delivery in vitro and in vivo

ChemMedChem ◽  
2017 ◽  
Vol 12 (21) ◽  
pp. 1768-1775 ◽  
Author(s):  
Baoji Du ◽  
Xiaoxiao Gu ◽  
Xu Han ◽  
Guanyu Ding ◽  
Yuling Wang ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Folic Acid ◽  
Gene Delivery ◽  
Targeted Gene Delivery ◽  
Gene Vectors

scholarly journals Programmably tiling rigidified DNA brick on gold nanoparticle as multi-functional shell for cancer-targeted delivery of siRNAs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chang Xue ◽  
Shuyao Hu ◽  
Zhi-Hua Gao ◽  
Lei Wang ◽  
Meng-Xue Luo ◽  
...  
Keyword(s):  
Gold Nanoparticle ◽  
Targeted Delivery ◽  
Target Genes ◽  
Sirna Delivery ◽  
Three Dimensional ◽  
Drug Carriers ◽  
High Serum ◽  
Exterior Surface

AbstractSmall interfering RNA (siRNA) is an effective therapeutic to regulate the expression of target genes in vitro and in vivo. Constructing a siRNA delivery system with high serum stability, especially responsive to endogenous stimuli, remains technically challenging. Herein we develop anti-degradation Y-shaped backbone-rigidified triangular DNA bricks with sticky ends (sticky-YTDBs) and tile them onto a siRNA-packaged gold nanoparticle in a programmed fashion, forming a multi-functional three-dimensional (3D) DNA shell. After aptamers are arranged on the exterior surface, a biocompatible siRNA-encapsulated core/shell nanoparticle, siRNA/Ap-CS, is achieved. SiRNAs are internally encapsulated in a 3D DNA shell and are thus protected from enzymatic degradation by the outermost layer of YTDB. The siRNAs can be released by endogenous miRNA and execute gene silencing within tumor cells, causing cell apoptosis higher than Lipo3000/siRNA formulation. In vivo treatment shows that tumor growth is completely (100%) inhibited, demonstrating unique opportunities for next-generation anticancer-drug carriers for targeted cancer therapies.

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