Size- and Surface- Dual Engineered Small Polyplexes for Efficiently Targeting Delivery of siRNA

Though siRNA-based therapy has achieved great progress, efficient siRNA delivery remains a challenge. Here, we synthesized a copolymer PAsp(-N=C-PEG)-PCys-PAsp(DETA) consisting of a poly(aspartate) block grafted with comb-like PEG side chains via a pH-sensitive imine bond (PAsp(-N=C-PEG) block), a poly(l-cysteine) block with a thiol group (PCys block), and a cationic poly(aspartate) block grafted with diethylenetriamine (PAsp(DETA) block). The cationic polymers efficiently complexed siRNA into polyplexes, showing a sandwich-like structure with a PAsp(-N=C-PEG) out-layer, a crosslinked PCys interlayer, and a complexing core of siRNA and PAsp(DETA). Low pH-triggered breakage of pH-sensitive imine bonds caused PEG shedding. The disulfide bond-crosslinking and pH-triggered PEG shedding synergistically decreased the polyplexes’ size from 75 nm to 26 nm. To neutralize excessive positive charges and introduce the targeting ligand, the polyplexes without a PEG layer were coated with an anionic copolymer modified with the targeting ligand lauric acid. The resulting polyplexes exhibited high transfection efficiency and lysosomal escape capacity. This study provides a promising strategy to engineer the size and surface of polyplexes, allowing long blood circulation and targeted delivery of siRNA.

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Nano Technological Approach for Anti-Tumor Therapy: Opportunities and Challenges

Nanoscience &Nanotechnology-Asia ◽

10.2174/2210681210666200213121156 ◽

2020 ◽

Vol 10 ◽

Author(s):

Krishna Champaneria ◽

Prajesh Prajapati

Keyword(s):

Adverse Effects ◽

Tumor Cells ◽

Targeted Delivery ◽

Blood Circulation ◽

Review Paper ◽

Tumor Therapy ◽

Conventional Chemotherapy ◽

Targeting Delivery ◽

Tumor Accumulation ◽

Work Done

Cancer is one of the reason for mortality and its individual and collective impact is substantial. Conventional chemotherapy utilizes drugs that can destroy Tumor cells effectively. But these agents destroy healthy cells along with the tumor cells, leading to many adverse effects which include hypersensitivity reactions, nephrotoxicity, and neurotoxicity. To minimize the adverse effects, various drug delivery systems (DDSs) has been developed. Among them, nanoparticles are attractive platforms for it. So this review paper explores the recent work done on targeted delivery, enhancing tumor accumulation and longer blood circulation using more effective biomaterial that will enhance the properties of nanoparticles. Moreover, various target-specific delivery of drugs like antibody-targeted, targeting delivery through angiogenesis, mitochondria, CD44 receptor are also explained.

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A peptide-targeted delivery system with pH-sensitive amphiphilic cell membrane disruption for efficient receptor-mediated siRNA delivery

Journal of Controlled Release ◽

10.1016/j.jconrel.2008.11.010 ◽

2009 ◽

Vol 134 (3) ◽

pp. 207-213 ◽

Cited By ~ 54

Author(s):

Xu-Li Wang ◽

Rongzuo Xu ◽

Zheng-Rong Lu

Keyword(s):

Cell Membrane ◽

Delivery System ◽

Targeted Delivery ◽

Sirna Delivery ◽

Ph Sensitive ◽

Membrane Disruption ◽

Cell Membrane Disruption ◽

Targeted Delivery System

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Non-Viral Delivery System and Targeted Bone Disease Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms20030565 ◽

2019 ◽

Vol 20 (3) ◽

pp. 565 ◽

Cited By ~ 7

Author(s):

Abdul Qadir ◽

Yongguang Gao ◽

Patil Suryaji ◽

Ye Tian ◽

Xiao Lin ◽

...

Keyword(s):

Delivery System ◽

Targeted Delivery ◽

Viral Vectors ◽

Transfection Efficiency ◽

Calcium Phosphates ◽

Delivery Systems ◽

Cationic Lipids ◽

Cationic Polymers ◽

Bone Disorders ◽

High Doses

Skeletal systems provide support, movement, and protection to the human body. It can be affected by several life suffering bone disorders such as osteoporosis, osteoarthritis, and bone cancers. It is not an easy job to treat bone disorders because of avascular cartilage regions. Treatment with non-specific drug delivery must utilize high doses of systemic administration, which may result in toxicities in non-skeletal tissues and low therapeutic efficacy. Therefore, in order to overcome such limitations, developments in targeted delivery systems are urgently needed. Although the idea of a general targeted delivery system using bone targeting moieties like bisphosphonates, tetracycline, and calcium phosphates emerged a few decades ago, identification of carrier systems like viral and non-viral vectors is a recent approach. Viral vectors have high transfection efficiency but are limited by inducing immunogenicity and oncogenicity. Although non-viral vectors possess low transfection efficiency they are comparatively safe. A number of non-viral vectors including cationic lipids, cationic polymers, and cationic peptides have been developed and used for targeted delivery of DNA, RNA, and drugs to bone tissues or cells with successful consequences. Here we mainly discuss such various non-viral delivery systems with respect to their mechanisms and applications in the specific targeting of bone tissues or cells. Moreover, we discuss possible therapeutic agents that can be delivered against various bone related disorders.

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Tumor-penetrating peptide modified and pH-sensitive polyplexes for tumor targeted siRNA delivery

Polymer Chemistry ◽

10.1039/c6py00427j ◽

2016 ◽

Vol 7 (23) ◽

pp. 3857-3863 ◽

Cited By ~ 17

Author(s):

Guoyong Zhou ◽

Yongmin Xu ◽

Meiwan Chen ◽

Du Cheng ◽

Xintao Shuai

Keyword(s):

Transfection Efficiency ◽

Sirna Delivery ◽

Ph Sensitive ◽

High Transfection Efficiency ◽

Intratumoral Delivery

The pH-sensitive copolymer enhanced the lysosome escape of polyplexes and modification of iRGD endowed the polyplexes with effective intratumoral delivery and high transfection efficiency.

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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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Targeted Delivery of siRNA Therapeutics using Ligand Mediated Biodegradable Polymeric Nanocarriers

Current Pharmaceutical Design ◽

10.2174/1381612824666180702113345 ◽

2018 ◽

Vol 24 (16) ◽

pp. 1788-1800 ◽

Cited By ~ 1

Author(s):

Kye-Soo Cho ◽

Seo-Jin Hong ◽

Min-Hye Ahn ◽

Sukdeb Pal ◽

Pill-Hoon Choung ◽

...

Keyword(s):

Cancer Treatment ◽

Delivery System ◽

Targeted Delivery ◽

Sirna Delivery ◽

Public Health Issue ◽

Magic Bullet ◽

Bodily Fluids ◽

Low Cytotoxicity ◽

Genetic And Environmental Factors ◽

Sirna Delivery System

Background: Cancer poses a major public health issue, is linked with high mortality rates across the world, and shows a strong interplay between genetic and environmental factors. To date, common therapeutics, including chemotherapy, immunotherapy, and radiotherapy, have made significant contributions to cancer treatment, although diverse obstacles for achieving the permanent “magic bullet” cure have remained. Recently, various anticancer therapeutic agents designed to overcome the limitations of these conventional cancer treatments have received considerable attention. One of these promising and novel agents is the siRNA delivery system; however, poor cellular uptake and altered siRNA stability in physiological environments have limited its use in clinical trials. Therefore, developing the ideal siRNA delivery system with low cytotoxicity, improved siRNA stability in the body’s circulation, and prevention of its rapid clearance from bodily fluids, is rapidly emerging as an innovative therapeutic strategy to combat cancer. Moreover, active targeting using ligand moieties which bind to over-expressed receptors on the surface of cancer cells would enhance the therapeutic efficiency of siRNA. Conclusion: In this review, we provide 1) an overview of the non-viral carrier associated with siRNA delivery for cancer treatment, and 2) a description of the five major cancer-targeting ligands.

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pH-sensitive zwitterionic polycarboxybetaine as a potential non-viral vector for small interfering RNA delivery

RSC Advances ◽

10.1039/d0ra09359a ◽

2020 ◽

Vol 10 (73) ◽

pp. 45059-45066

Author(s):

Huan Peng ◽

Weihong Ji ◽

Ruichen Zhao ◽

Zhiguo Lu ◽

Jun Yang ◽

...

Keyword(s):

Small Interfering Rna ◽

Viral Vector ◽

Sirna Delivery ◽

Ph Sensitive ◽

Acidic Environment ◽

Interfering Rna

pH-sensitive zwitterionic polycarboxybetaine could complex siRNA in an acidic environment and could be used as a non-viral vector for safe siRNA delivery.

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