Gene therapy vectors for targeting the heart

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Targeted Delivery ◽  
Specific Binding ◽  
Target Cells ◽  
Biological Targets ◽  
Drug Delivery Vehicles ◽  
Therapeutic Drugs ◽  
Gene Therapy Vectors ◽  
Delivery Vehicles ◽  
Selective Delivery ◽  
Targeted Medicine

The delivery of therapeutic drugs to the heart continues to be a challenge. Developing precise strategies to target the heart is equally as important as discovering new therapeutic medications. To grow this sector, a program that focuses on targeted delivery to the heart, as well as efforts to improve cardiac selectivity and retention of therapeutic medications, may be required. Targeted medicine distribution is one of the most important and unresolved issues in pharmacology. Viruses, on the other hand, have evolved unique and extremely accurate tropisms toward their biological targets through the usage of specific binding proteins. The inclusion of these viral proteins into the plasma membrane of EVs should improve the efficiency with which EVs transport drugs to target cells. Understanding the structure, content, and mechanisms of exosome–cell interactions and uptake might also help with the creation of bioengineered exosomes and other EVs that might be used as targeted drug delivery vehicles. In addition to establishing the optimal vector for each therapeutic ingredient, effective clinical translation of cardiac medicines requires minimally invasive yet highly selective delivery techniques.

scholarly journals Single Chain Variable Fragment Fused to Maltose Binding Protein: A Modular Nanocarrier Platform for the Targeted Delivery of Antitumorals

2021 ◽  
Author(s):  
Francisco J. Reche-Perez ◽  
Simona Plesselova ◽  
Eduardo De los Reyes-Berbel ◽  
Mariano Ortega-Muñoz ◽  
F. Javier Lopez-Jaramillo ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Targeted Delivery ◽  
Specific Binding ◽  
Protein A ◽  
Antibody Fragments ◽  
Single Chain Variable Fragment ◽  
Single Chain ◽  
Binding Properties ◽  
Single Chain Variable Fragments ◽  
Selective Delivery

The use of the specific binding properties of monoclonal antibody fragments such as single-chain variable fragments (ScFv) for the selective delivery of antitumor therapeutics for cancer cells is attractive due...

scholarly journals Well-defined single polymer nanoparticles for the antibody-targeted delivery of chemotherapeutic agents

2015 ◽  
Vol 6 (8) ◽  
pp. 1286-1299 ◽  
Author(s):  
D. D. Lane ◽  
D. Y. Chiu ◽  
F. Y. Su ◽  
S. Srinivasan ◽  
H. B. Kern ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Targeted Delivery ◽  
Raft Polymerization ◽  
Chemotherapeutic Agents ◽  
Polymer Nanoparticles ◽  
Drug Delivery Vehicles ◽  
Molecular Weights ◽  
Delivery Vehicles ◽  
Targeted Drug

Second generation polymeric brushes with molecular weights in excess of 106 Da were synthesize via RAFT polymerization for use as antibody targeted drug delivery vehicles.

scholarly journals Cryo-shocked cancer cells for targeted drug delivery and vaccination

2020 ◽  
Vol 6 (50) ◽  
pp. eabc3013
Author(s):  
Tianyuan Ci ◽  
Hongjun Li ◽  
Guojun Chen ◽  
Zejun Wang ◽  
Jinqiang Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Cells ◽  
Liquid Nitrogen ◽  
Targeted Drug Delivery ◽  
Targeted Delivery ◽  
Myeloid Leukemia ◽  
Live Cells ◽  
Simple Method ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles

Live cells have been vastly engineered into drug delivery vehicles to leverage their targeting capability and cargo release behavior. Here, we describe a simple method to obtain therapeutics-containing “dead cells” by shocking live cancer cells in liquid nitrogen to eliminate pathogenicity while preserving their major structure and chemotaxis toward the lesion site. In an acute myeloid leukemia (AML) mouse model, we demonstrated that the liquid nitrogen–treated AML cells (LNT cells) can augment targeted delivery of doxorubicin (DOX) toward the bone marrow. Moreover, LNT cells serve as a cancer vaccine and promote antitumor immune responses that prolong the survival of tumor-bearing mice. Preimmunization with LNT cells along with an adjuvant also protected healthy mice from AML cell challenge.

scholarly journals Drug-delivery and multifunction possibilities of hypocrellin photosensitizers

2015 ◽  
Vol 08 (01) ◽  
pp. 1530003 ◽  
Author(s):  
Hong Deng ◽  
Jie Xie ◽  
Jingquan Zhao
Keyword(s):  
Drug Delivery ◽  
Specific Binding ◽  
Intramolecular Proton Transfer ◽  
Cellular Level ◽  
Photodynamic Diagnosis ◽  
Delivery Problem ◽  
Drug Delivery Vehicles ◽  
Over Expression ◽  
Normal Tissues ◽  
Delivery Vehicles

Photodynamic therapy (PDT) has been a routine treatment of tumors and some microvascular diseases, but clinically available photosensitizers are still scarce. Among all kinds of photosensitizers, hypocrellins possess the most characteristics of ideal photosensitizers, such as, high photo-activity but low dark toxicity, fast clearance from tissues. This review is focused on two main topics, drug-delivery problem of hypocrellins and how the environment-sensitive fluorescence of hypocrellins was used for recognition of various biomolecules. Drug-delivery of hypocrellins was mainly achieved in two strategies — preparing the drug-delivery vehicles and finding quantitatively amphiphilic derivatives. Hypocrellin fluorescence originated from the intramolecular proton transfer is very distinct from other kinds of photosensitizers. Recently, it was proved that quantitative hypocrellin fluorescence could not only recognize various biomolecules, including proteins, polysaccharides and lipids, but also distinguish the specific binding from nonspecific binding with some kind of biomolecules. Meantime, hypocrellin fluorescence was pH-sensitive. It is known that tumor cells or tissues have the features of a large amount of lipid, neonatal collagen, over-expression of polysaccharides, and lower pH values compared to normal tissues. According to the relative but not absolute specificity, further studies on quantitative recognition of various biomolecules at a cellular level, may find a new clue to treat tumors by joint usage of photodynamic diagnosis (PDD) and PDT.

scholarly journals Nano-Biomimetic Drug Delivery Vehicles: Potential Approaches for COVID-19 Treatment

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5952
Author(s):  
Bwalya A. Witika ◽  
Pedzisai A. Makoni ◽  
Larry L. Mweetwa ◽  
Pascal V. Ntemi ◽  
Melissa T. R. Chikukwa ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Charge Composition ◽  
Drug Delivery Vehicles ◽  
Therapeutic Outcomes ◽  
Delivery Vehicles ◽  
The Impact

The current COVID-19 pandemic has tested the resolve of the global community with more than 35 million infections worldwide and numbers increasing with no cure or vaccine available to date. Nanomedicines have an advantage of providing enhanced permeability and retention and have been extensively studied as targeted drug delivery strategies for the treatment of different disease. The role of monocytes, erythrocytes, thrombocytes, and macrophages in diseases, including infectious and inflammatory diseases, cancer, and atherosclerosis, are better understood and have resulted in improved strategies for targeting and in some instances mimicking these cell types to improve therapeutic outcomes. Consequently, these primary cell types can be exploited for the purposes of serving as a “Trojan horse” for targeted delivery to identified organs and sites of inflammation. State of the art and potential utilization of nanocarriers such as nanospheres/nanocapsules, nanocrystals, liposomes, solid lipid nanoparticles/nano-structured lipid carriers, dendrimers, and nanosponges for biomimicry and/or targeted delivery of bioactives to cells are reported herein and their potential use in the treatment of COVID-19 infections discussed. Physicochemical properties, viz., hydrophilicity, particle shape, surface charge, composition, concentration, the use of different target-specific ligands on the surface of carriers, and the impact on carrier efficacy and specificity are also discussed.

scholarly journals Biosynthesis and Immobilization of Biofunctional Allophycocyanin

2011 ◽  
Vol 2011 ◽  
pp. 1-6
Author(s):  
Yingjie Chen ◽  
Shaofang Liu ◽  
Yulin Cui ◽  
Peng Jiang ◽  
Huaxin Chen ◽  
...  
Keyword(s):  
Magnetic Nanoparticles ◽  
Targeted Delivery ◽  
Metal Ion ◽  
Binding Ability ◽  
Drug Delivery Vehicles ◽  
His Tag ◽  
Delivery Vehicles ◽  
Chelating Ability ◽  
Potential Strategy ◽  
Streptavidin Binding

The holo-allophycocyanin-αsubunit, which has various reported pharmacological uses, was biosynthesized with both Strep-II-tag and His-tag at the N-terminal inEscherichia coli. The streptavidin-binding ability resulting from the Strep II-tag was confirmed by Western blot. Additionally, the metal-chelating ability deriving from the His-tag not only facilitated its purification by immobilized metal-ion affinity chromatography but also promoted its immobilization on Zn (II)-decorated silica-coated magnetic nanoparticles. The holo-allophycocyanin-αsubunit with streptavidin-binding ability was thereby immobilized on magnetic nanoparticles. Magnetic nanoparticles are promising as drug delivery vehicles for targeting and locating at tumors. Thus, based on genetic engineering and nanotechnology, we provide a potential strategy to facilitate the biomodification and targeted delivery of pharmacological proteins.

scholarly journals EV Cargo Sorting in Therapeutic Development for Cardiovascular Disease

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1500
Author(s):  
Cherrie D. Sherman ◽  
Shweta Lodha ◽  
Susmita Sahoo
Keyword(s):  
Cardiovascular Disease ◽  
Biological Molecules ◽  
Bioactive Molecules ◽  
Therapeutic Interventions ◽  
Target Cells ◽  
Drug Delivery Vehicles ◽  
Therapeutic Delivery ◽  
Therapeutic Development ◽  
Delivery Vehicles ◽  
Cargo Sorting

Cardiovascular disease remains the leading cause of morbidity and mortality in the world. Thus, therapeutic interventions to circumvent this growing burden are of utmost importance. Extracellular vesicles (EVs) actively secreted by most living cells, play a key role in paracrine and endocrine intercellular communication via exchange of biological molecules. As the content of secreted EVs reflect the physiology and pathology of the cell of their origin, EVs play a significant role in cellular homeostasis, disease pathogenesis and diagnostics. Moreover, EVs are gaining popularity in clinics as therapeutic and drug delivery vehicles, transferring bioactive molecules such as proteins, genes, miRNAs and other therapeutic agents to target cells to treat diseases and deter disease progression. Despite our limited but growing knowledge of EV biology, it is imperative to understand the complex mechanisms of EV cargo sorting in pursuit of designing next generation EV-based therapeutic delivery systems. In this review, we highlight the mechanisms of EV cargo sorting and methods of EV bioengineering and discuss engineered EVs as a potential therapeutic delivery system to treat cardiovascular disease.

Lipid-based Vehicles for siRNA Delivery in Biomedical Field

2020 ◽  
Vol 21 (1) ◽  
pp. 3-22
Author(s):  
Tianzhong Li ◽  
Linfeng Huang ◽  
Mengsu Yang
Keyword(s):  
Targeted Delivery ◽  
Genetic Diseases ◽  
Sirna Delivery ◽  
Surface Modifications ◽  
Small Interference Rna ◽  
Drug Delivery Vehicles ◽  
The Past ◽  
Different Types ◽  
Delivery Vehicles ◽  
Biomedical Field

Background: Genetic drugs have aroused much attention in the past twenty years. RNA interference (RNAi) offers novel insights into discovering potential gene functions and therapies targeting genetic diseases. Small interference RNA (siRNA), typically 21-23 nucleotides in length, can specifically degrade complementary mRNA. However, targeted delivery and controlled release of siRNA remain a great challenge. Methods: Different types of lipid-based delivery vehicles have been synthesized, such as liposomes, lipidoids, micelles, lipoplexes and lipid nanoparticles. These carriers commonly have a core-shell structure. For active targeting, ligands may be conjugated to the surface of lipid particles. Results: Lipid-based drug delivery vehicles can be utilized in anti-viral or anti-tumor therapies. They can also be used to tackle genetic diseases or discover novel druggable genes. Conclusion: In this review, the structures of lipid-based vehicles and possible surface modifications are described, and applications of delivery vehicles in biomedical field are discussed.

scholarly journals Reversible Masking Using Low-Molecular-Weight Neutral Lipids to Achieve Optimal-Targeted Delivery

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Nancy Smyth Templeton ◽  
Neil Senzer
Keyword(s):  
Molecular Weight ◽  
Targeted Delivery ◽  
Neutral Lipids ◽  
Metastatic Cancer ◽  
Target Cells ◽  
Low Molecular Weight ◽  
Specific Cell ◽  
Surface Receptors ◽  
Normal Tissues ◽  
Delivery Vehicles

Intravenous injection of therapeutics is required to effectively treat or cure metastatic cancer, certain cardiovascular diseases, and other acquired or inherited diseases. Using this route of delivery allows potential uptake in all disease targets that are accessed by the bloodstream. However, normal tissues and organs also have the potential for uptake of therapeutic agents. Therefore, investigators have used targeted delivery to attempt delivery solely to the target cells; however, use of ligands on the surface of delivery vehicles to target specific cell surface receptors is not sufficient to avoid nonspecific uptake. PEGylation has been used for decades to try to avoid nonspecific uptake but suffers from many problems known as “The PEGylation Dilemma.” We have solved this dilemma by replacing PEGylation with reversible masking using low-molecular-weight neutral lipids in order to achieve optimal-targeted delivery solely to target cells. Our paper will focus on this topic.

scholarly journals Therapeutic potential of functionalized siRNA nanoparticles on regression of liver cancer in experimental mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Azmat Ali Khan ◽  
Amer M. Alanazi ◽  
Mumtaz Jabeen ◽  
Arun Chauhan ◽  
Mohammad Azam Ansari
Keyword(s):  
Targeted Delivery ◽  
Therapeutic Potential ◽  
Survivin Expression ◽  
Significant Inhibition ◽  
Target Cells ◽  
Specific Gene ◽  
Antitumor Potential ◽  
Effective Delivery ◽  
Selective Delivery ◽  
Interfering Rna

Abstract Short interfering RNA (siRNA) possesses special ability of silencing specific gene. To increase siRNA stability, transportation and its uptake by tumor cells, effective delivery to the appropriate target cells is a major challenge of siRNA-based therapy. In the present study, an effective, safe and biocompatible survivin siRNA encapsulated, GalNAc decorated PEGylated PLGA nanoconjugates (NCs) viz., GalNAc@PEG@siRNA-PLGA were engineered and their synergistic antitumor efficacy was evaluated for targeted delivery in HCC bearing experimental mice. GalNAc@PEG@siRNA-PLGA NCs were characterized for size, bioavailability, toxicity and biocompatibility. Their antitumor potential was evaluated considering gene silencing, apoptosis, histopathology and survival of treated mice. Exceptional accumulation of hepatocytes, reduction in survivin expression and prominent regression in tumor size confirmed the ASGPR-mediated uptake of ligand-anchored NCs and silencing of survivin gene in a targeted manner. Increased DNA fragmentation and potential modulation of caspase-3, Bax and Bcl-2 factors specified the induction of apoptosis that helped in significant inhibition of HCC progression. The potential synchronous and tumor selective delivery of versatile NCs indicated the effective payloads towards the target site, increased apoptosis in cancer cells and improved survival of treated animals.

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