scholarly journals Biophysical characterization of DNA origami nanostructures reveals inaccessibility to intercalation binding sites

2019 ◽  
Author(s):  
Helen L. Miller ◽  
Sonia Contera ◽  
Adam J.M. Wollman ◽  
Adam Hirst ◽  
Katherine E. Dunn ◽  
...  

AbstractIntercalation of drug molecules into synthetic DNA nanostructures formed through self-assembled origami has been postulated as a valuable future method for targeted drug delivery. This is due to the excellent biocompatibility of synthetic DNA nanostructures, and high potential for flexible programmability including facile drug release into or near to target cells. Such favourable properties may enable high initial loading and efficient release for a predictable number of drug molecules per nanostructure carrier, important for efficient delivery of safe and effective drug doses to minimise non-specific release away from target cells. However, basic questions remain as to how intercalation-mediated loading depends on the DNA carrier structure. Here we use the interaction of dyes YOYO-1 and acridine orange with a tightly-packed 2D DNA origami tile as a simple model system to investigate intercalation-mediated loading. We employed multiple biophysical techniques including single-molecule fluorescence microscopy, atomic force microscopy, gel electrophoresis and controllable damage using low temperature plasma on synthetic DNA origami samples. Our results indicate that not all potential DNA binding sites are accessible for dye intercalation, which has implications for future DNA nanostructures designed for targeted drug delivery.

Author(s):  
Manzoor A. Mir ◽  
Basharat A. Bhat ◽  
Bashir A. Sheikh ◽  
Gulzar Ahmed Rather ◽  
Safiya Mehraj ◽  
...  

The 21st century has seen a massive spring up in the applications of nanobiotechnology. Incorporation of functionalized and modified nanostructures in various biomedical applications has generated significant research interests such as implant and tissue engineering, diagnosis, and therapy, thereby aiding in improvement of human health. The unique properties of nanoparticles including non-toxicity and biocompatibility with a large surface area make it possible to modify their surface with different chemicals including different polymers, antibodies, and drug molecules. Therefore, they are utilized for targeted drug delivery in order to carry drugs and selectively release them in desired tissues which reduces destructive effects on healthy cells. This chapter mainly covers the basic properties of nanoparticles including nanomedicine, their preparation and focuses on their diagnosis, and therapeutic applications in disease including cancer and other challenging ailments.


Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4758
Author(s):  
Cristina Moraru ◽  
Manuela Mincea ◽  
Gheorghita Menghiu ◽  
Vasile Ostafe

Chitosan is a polymer that is extensively used to prepare nanoparticles (NPs) with tailored properties for applications in many fields of human activities. Among them, targeted drug delivery, especially when cancer therapy is the main interest, is a major application of chitosan-based NPs. Due to its positive charges, chitosan is used to produce the core of the NPs or to cover NPs made from other types of polymers, both strategies aiming to protect the carried drug until NPs reach the target sites and to facilitate the uptake and drug delivery into these cells. A major challenge in the design of these chitosan-based NPs is the formation of a protein corona (PC) upon contact with biological fluids. The composition of the PC can, to some extent, be modulated depending on the size, shape, electrical charge and hydrophobic/hydrophilic characteristics of the NPs. According to the composition of the biological fluids that have to be crossed during the journey of the drug-loaded NPs towards the target cells, the surface of these particles can be changed by covering their core with various types of polymers or with functionalized polymers carrying some special molecules, that will preferentially adsorb some proteins in their PC. The PC’s composition may change by continuous processes of adsorption and desorption, depending on the affinity of these proteins for the chemical structure of the surface of NPs. Beside these, in designing the targeted drug delivery NPs one can take into account their toxicity, initiation of an immune response, participation (enhancement or inhibition) in certain metabolic pathways or chemical processes like reactive oxygen species, type of endocytosis of target cells, and many others. There are cases in which these processes seem to require antagonistic properties of nanoparticles. Products that show good behavior in cell cultures may lead to poor in vivo results, when the composition of the formed PC is totally different. This paper reviews the physico-chemical properties, cellular uptake and drug delivery applications of chitosan-based nanoparticles, specifying the factors that contribute to the success of the targeted drug delivery. Furthermore, we highlight the role of the protein corona formed around the NP in its intercellular fate.


Small ◽  
2020 ◽  
Vol 16 (16) ◽  
pp. 1904857 ◽  
Author(s):  
Zhilei Ge ◽  
Linjie Guo ◽  
Guangqi Wu ◽  
Jiang Li ◽  
Yunlong Sun ◽  
...  

2018 ◽  
Vol 8 (5-s) ◽  
pp. 100-104 ◽  
Author(s):  
Abhay Kumar

Novel drug delivery systems are now a day is creating a new interest in development of drug deliveries. The transdermal route of drug delivery has gained great interest of pharmaceutical research, as it circumvents number of problems associated with oral route of drug administration. Transferosomes are capable of transdermal delivery of low as well as high molecular weight drugs. This offers several potential advantages over conventional routes like avoidance of first pass metabolism, predictable and extended duration of activity, minimizing undesirable side effects, utility of short half life drugs, improving physiological and pharmacological response and have been applied to increases the efficiency of the material transfer across the intact skin, by the use of penetration enhancers and non-ionic surfactant vesicles. It is suitable for controlled and targeted drug delivery and it can accommodate drug molecules with wide range of solubility. Due to its high deformability it gives better penetration of intact vesicles. Transferosome possess an infrastructure consisting of hydrophobic and hydrophilic moieties together and as a result can accommodate drug molecules with wide range of solubility. They are biocompatible and biodegradable as they are made from natural phospholipids and have high entrapment efficiency. In this review, we have focused on transferosome with discussions on novel drug delivery systems for targeted delivery of therapeutics and important issues and challenges for future clinical applications. Keywords: Novel drug delivery systems, Transferosomes, Transdermal drug delivery, Targeted drug delivery


Author(s):  
ADE IRMA SURYANI ◽  
NASRUL WATHONI ◽  
MUCHTARIDI MUCHTARIDI ◽  
I. MADE JONI

This review aimed to determine the potential of the combination of chitosan and alginate as a targeted drug carrier in cancer therapy. This article is based on the results of previous research journals collected from Google Scholar, Scopus, PubMed and Science Direct sites using the keywords chitosan, alginate, targeted drug delivery for cancer, nanoparticle chitosan alginate. With the inclusion criteria, only English-language journals, journals published in the last 10 y, related to chitosan and alginate-based formulations. Meanwhile, the exclusion criteria were journals on pharmacological properties and bioactivity, food and cosmetics. The combination of cationic chitosan and anionic alginate forming strong cross-links showed good mucoadhesive properties, higher resistance to low pH and high-efficiency encapsulation without showing any obvious cytotoxicity. Ch/Alg can overcome the shortcomings of the active substance, such as its rapid release process and the required active ingredient is lower than that required to enter the cancer target cells so as to minimize side effects of the drug by providing drug-induced release. in response to various stimuli that are well suited to the intended purpose, such as pH stimuli, redox gradients, light, temperature, and magnetism. It is shown that the combination of chitosan and alginate base has great potential in targeting cancer therapy by increasing its therapeutic effectiveness and selectivity.


Author(s):  
Debaleena Das ◽  
Nivedita Maity ◽  
Anuradha H. V.

Targeted drug delivery is a method of delivering medication in a unique way so that the concentration of the drug at the target site is optimized, burden of the drug to other tissues is reduced and toxicity minimized. There are various novel approaches to deliver drugs to the target sites in the form of nanocapsules, nanocrystals, nanoemulsions, dendrimers, polymeric micelles, nanotubes and monoclonal antibodies. They have the advantages of improved bioavailability, facilitated transport of drugs across difficult barriers to reach the target tissues for a specific action and providing protection to protect the drug against degradation. A number of anticancer drugs like Doxorubicin, Paclitaxel and 5-Fluorouracil have been formulated using nanoparticles. These innovative techniques have helped to overcome the limitations like resistance in the target cells and difficulty in movement across the barriers which are seen in the conventional drug delivery system. Apart from being a therapeutic tool, it also has brought revolution in early diagnosis of diseases and gene transfer. The surge of nanotechnology is now being translated into commercialized products. The future is exciting, and the promises are limitless as the application of nanotechnology in medicine will provide remarkable opportunities and newer perspectives for novel and effective treatment in various diseases. 


2020 ◽  
Vol 8 (3) ◽  
pp. 492-503 ◽  
Author(s):  
Jianqin Yan ◽  
Jun Chen ◽  
Nan Zhang ◽  
Yidi Yang ◽  
Wangwei Zhu ◽  
...  

d-(KLAKLAK)2-and Cy5-modified tetrahedral DNA nanostructures for imaging-guided mitochondria-targeted drug delivery


2020 ◽  
Vol 20 (27) ◽  
pp. 2472-2492
Author(s):  
Le-Yi Zhang ◽  
Xue Yang ◽  
Shi-Bing Wang ◽  
Hong Chen ◽  
Hong-Ying Pan ◽  
...  

Extracellular vesicles (EVs) are membrane vesicles (MVs) playing important roles in various cellular and molecular functions in cell-to-cell signaling and transmitting molecular signals to adjacent as well as distant cells. The preserved cell membrane characteristics in MVs derived from live cells, give them great potential in biological applications. EVs are nanoscale particulates secreted from living cells and play crucial roles in several important cellular functions both in physiological and pathological states. EVs are the main elements in intercellular communication in which they serve as carriers for various endogenous cargo molecules, such as RNAs, proteins, carbohydrates, and lipids. High tissue tropism capacity that can be conveniently mediated by surface molecules, such as integrins and glycans, is a unique feature of EVs that makes them interesting candidates for targeted drug delivery systems. The cell-derived giant MVs have been exploited as vehicles for delivery of various anticancer agents and imaging probes and for implementing combinational phototherapy for targeted cancer treatment. Giant MVs can efficiently encapsulate therapeutic drugs and deliver them to target cells through the membrane fusion process to synergize photodynamic/photothermal treatment under light exposure. EVs can load diagnostic or therapeutic agents using different encapsulation or conjugation methods. Moreover, to prolong the blood circulation and enhance the targeting of the loaded agents, a variety of modification strategies can be exploited. This paper reviews the EVs-based drug delivery strategies in cancer therapy. Biological, pharmacokinetics and physicochemical characteristics, isolation techniques, engineering, and drug loading strategies of EVs are discussed. The recent preclinical and clinical progresses in applications of EVs and oncolytic virus therapy based on EVs, the clinical challenges and perspectives are discussed.


2019 ◽  
Vol 15 (4) ◽  
pp. 382-397 ◽  
Author(s):  
Shashiprabha Punyakantha Dunuweera ◽  
Rajapakse Mudiyanselage Shashanka Indeevara Rajapakse ◽  
Rajapakshe Babilage Sanjitha Dilan Rajapakshe ◽  
Sudu Hakuruge Dilan Priyankara Wijekoon ◽  
Mallika Gedara Gayan Sasanka Nirodha Thilakarathna ◽  
...  

Targeted drug delivery (TDD) is an advanced and smart method of delivering drugs to the patients in a targeted sequence that increases the concentration of delivered drug only at the targeted body part of interest (organs/tissues/cells). This will in turn enhance efficacy of treatment by reducing side effects and the required dose of the drug. TDD ensures a certain defined minimally required constant amount of a therapeutic agent for a prolonged period of time to a targeted diseased area within the body. This helps maintain the required plasma and tissue drug levels in the body thereby avoiding any damage to the healthy tissue via the drug. Various drug carriers that are envisaged in advanced delivery systems are soluble polymers, inorganic nanoparticles, magnetic nanoparticles, biodegradable microsphere polymers (synthetic and natural), neutrophils, fibroblasts, artificial cells, lipoproteins, liposomes, micelles and immune micelle. In selecting such a vehicle, important factors to consider are chemical and physical properties drugs, side effects or cytotoxicity to healthy cells, route to be taken for the delivery of the drug, the targeted site, and the disease. As such, TDD formulations are prepared by considering the specific properties of target cells, nature of markers or transport carriers or vehicles, which convey drug to specific receptors, and ligands and physically modulated components.


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