Loading of DOX into a tetrahedron DNA nanostructure: The corner does matter

The rapid development of multidrug co-delivery and nano-medicines has made spontaneous progress in tumor treatment and diagnosis. DNA is a unique biological molecule that can be tailored and molded into various nanostructures. The addition of ligands or stimuli-responsive elements enables DNA nanostructures to mediate highly targeted drug delivery to the cancer cells. Smart DNA nanostructures, owing to their various shapes, sizes, geometry, sequences, and characteristics, have various modes of cellular internalization and final disposition. On the other hand, functionalized DNA nanocarriers have specific receptor-mediated uptake, and most of these ligand anchored nanostructures able to escape lysosomal degradation. DNA-based and stimuli responsive nano-carrier systems are the latest advancement in cancer targeting. The data exploration from various studies demonstrated that the DNA nanostructure and stimuli responsive drug delivery systems are perfect tools to overcome the problems existing in the cancer treatment including toxicity and compromised drug efficacy. In this light, the review summarized the insights about various types of DNA nanostructures and stimuli responsive nanocarrier systems applications for diagnosis and treatment of cancer.

Download Full-text

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

10.1101/845420 ◽

2019 ◽

Author(s):

Helen L. Miller ◽

Sonia Contera ◽

Adam J.M. Wollman ◽

Adam Hirst ◽

Katherine E. Dunn ◽

...

Keyword(s):

Drug Delivery ◽

Single Molecule ◽

Targeted Drug Delivery ◽

Binding Sites ◽

Dna Origami ◽

Target Cells ◽

Dna Nanostructures ◽

Synthetic Dna ◽

Drug Molecules ◽

Targeted Drug

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.

Download Full-text

FOLDNA, a Web Server for Self-Assembled DNA Nanostructure Autoscaffolds and Autostaples

Journal of Nanotechnology ◽

10.1155/2012/453953 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 3

Author(s):

Chensheng Zhou ◽

Heng Luo ◽

Xiaolu Feng ◽

Xingwang Li ◽

Jie Zhu ◽

...

Keyword(s):

Drug Delivery ◽

Dna Sequences ◽

Self Assembly ◽

Web Server ◽

Automatic Design ◽

Dna Nanostructures ◽

Complementary Dna ◽

Dna Nanostructure ◽

Comprehensive Information ◽

Self Assembled

DNA self-assembly is a nanotechnology that folds DNA into desired shapes. Self-assembled DNA nanostructures, also known as origami, are increasingly valuable in nanomaterial and biosensing applications. Two ways to use DNA nanostructures in medicine are to form nanoarrays, and to work as vehicles in drug delivery. The DNA nanostructures perform well as a biomaterial in these areas because they have spatially addressable and size controllable properties. However, manually designing complementary DNA sequences for self-assembly is a technically demanding and time consuming task, which makes it advantageous for computers to do this job instead. We have developed a web server, FOLDNA, which can automatically design 2D self-assembled DNA nanostructures according to custom pictures and scaffold sequences provided by the users. It is the first web server to provide an entirely automatic design of self-assembled DNA nanostructure, and it takes merely a second to generate comprehensive information for molecular experiments including: scaffold DNA pathways, staple DNA directions, and staple DNA sequences. This program could save as much as several hours in the designing step for each DNA nanostructure. We randomly selected some shapes and corresponding outputs from our server and validated its performance in molecular experiments.

Download Full-text

Ultrasound exposure enhances cellular uptake of nanoscale cargos

10.1101/2021.09.11.459898 ◽

2021 ◽

Author(s):

Kahkashan Bansal ◽

Anjali Rajwar ◽

Himanshu Shekhar ◽

Dhiraj Bhatia

Keyword(s):

Drug Delivery ◽

Cellular Uptake ◽

Propidium Iodide ◽

Dna Nanotechnology ◽

Chemotherapeutic Agents ◽

Dna Nanostructures ◽

Ultrasound Exposure ◽

Dna Nanostructure ◽

Cellular Components ◽

Further Development

DNA nanotechnology utilizes DNA as a structural molecule to design palette of nanostructures with different shapes and sizes. DNA nanocages have demonstrated significant potential for drug delivery. Therefore, enhancing the delivery of DNA nanocages into cells can improve their efficacy as drug delivery agents. Numerous studies have reported the effects of ultrasound for enhancing drug delivery across biological barriers. The mechanical bioeffects caused by cell-ultrasound interaction can cause sonoporation, leading to enhanced uptake of drugs, nanoparticles, and chemotherapeutic agents through membranes. Whether ultrasound exposure can enhance the delivery of DNA nanocages has not been explored, which is the focus of this study. Specifically, we investigated the effects of ultrasound on the cellular uptake of propidium Iodide, fluorescent dextrans, and DNA nanostructures). We provide evidence of modulation of pore formation in the cell membrane by ultrasound by studying the intracellular uptake of the impermeable dye, propidium iodide. Treatment of cells with low amplitudes of ultrasound enhanced the uptake of different sizes of dextrans and DNA based nanodevices. These findings could serve as the foundation for further development ultrasound-enabled DNA nanostructure delivery and for specific understanding of underlying biological mechanisms of interaction between ultrasound parameters and cellular components; the knowledge that can be further explored for potential biological and biomedical applications.

Download Full-text

Advances in DNA Nanostructure-Based Smart Drug Delivery Systems

Nano LIFE ◽

10.1142/s1793984417300011 ◽

2017 ◽

Vol 07 (01) ◽

pp. 1730001 ◽

Cited By ~ 2

Author(s):

Xingjie Hu ◽

Zejun Wang ◽

Chunhai Fan ◽

Haiyun Song

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Water Solubility ◽

Dna Nanotechnology ◽

Delivery Systems ◽

Structure Design ◽

Dna Nanostructures ◽

Cellular Delivery ◽

Nanoscale Systems ◽

Dna Nanostructure

Highly specific deoxyribonucleic acid (DNA) base-pairing not only carries genetic information, but also provides the basis for self-assembly of novel nanostructures with programmable shapes and sizes. Unlike single-stranded and double-stranded DNA, DNA nanostructures exhibit good cellular permeability. They also have characteristics of uniform size, easy functionalization, precise addressability, excellent water solubility and high biocompatibility. Due to their unique properties, these tailored molecular devices are ideal nanoscale systems for targeting cells and triggering cellular responses. Recent progress in the field of DNA nanotechnology has demonstrated effectiveness and advantages of DNA nanostructures as smart and targeted drug delivery systems or imaging agents within living organisms. In this review, we summarize the recent advances in structure design, cargo loading and cellular delivery of DNA nanocarriers, and discuss their potential in therapeutic applications.

Download Full-text

Advances in Molecularly Imprinted Polymers as Drug Delivery Systems

Molecules ◽

10.3390/molecules26123589 ◽

2021 ◽

Vol 26 (12) ◽

pp. 3589

Author(s):

Rui Liu ◽

Alessandro Poma

Keyword(s):

Drug Delivery ◽

Molecularly Imprinted Polymers ◽

Drug Loading ◽

Stimuli Responsive ◽

Molecularly Imprinted ◽

Imprinted Polymers ◽

Drug Delivery Vehicles ◽

The Past ◽

Drug Molecules ◽

Delivery Vehicles

Despite the tremendous efforts made in the past decades, severe side/toxic effects and poor bioavailability still represent the main challenges that hinder the clinical translation of drug molecules. This has turned the attention of investigators towards drug delivery vehicles that provide a localized and controlled drug delivery. Molecularly imprinted polymers (MIPs) as novel and versatile drug delivery vehicles have been widely studied in recent years due to the advantages of selective recognition, enhanced drug loading, sustained release, and robustness in harsh conditions. This review highlights the design and development of strategies undertaken for MIPs used as drug delivery vehicles involving different drug delivery mechanisms, such as rate-programmed, stimuli-responsive and active targeting, published during the course of the past five years.

Download Full-text

Nanoparticulate Drug Delivery Systems: An update

Research Journal of Pharmaceutical Dosage Forms and Technology ◽

10.52711/0975-4377.2021.00051 ◽

2021 ◽

pp. 312-316

Author(s):

Pandey Swarnima ◽

Sushant Kumar

Keyword(s):

Drug Delivery ◽

Carrying Capacity ◽

Drug Delivery Systems ◽

High Specificity ◽

Delivery Systems ◽

Classification Methods ◽

Hydrophobic Drug ◽

Drug Molecules ◽

Conventional Drug ◽

Novel Drug

The paper is aimed to provide a comprehensive review on nanoparticles, methods of preparation, applications in drug delivery. In recent years, there has been an exponential interest within the development of novel drug delivery systems using nanoparticles. Nanoparticles offers significant advantages over the conventional drug delivery in terms of high stability, high specificity, high drug carrying capacity, ability for controlled release, possibility to use in several route of administration and therefore the capability to deliver both hydrophilic and hydrophobic drug molecules. This review focuses on classification, methods of preparation, characterization, application, advantages of nanoparticles and health perspectives.

Download Full-text

Elucidating the Drug Release from Metal-Organic Framework Nanocomposites via in Situ Synchrotron Microspectroscopy and Theoretical Modelling

10.26434/chemrxiv.9975389 ◽

2019 ◽

Author(s):

Barbara Souza ◽

Lorenzo Dona ◽

Kirill Titov ◽

Paolo Bruzzese ◽

Zhixin Zeng ◽

...

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Density Functional ◽

Metal Organic Framework ◽

Density Functional Theory Calculations ◽

Theoretical Modelling ◽

Time Resolved ◽

Drug Molecules ◽

Metal Organic

Nanocomposites comprising metal-organic frameworks (MOFs) embedded in a polymeric matrix are promising carriers for drug delivery applications. While understanding the chemical and physical transformations of MOFs during the release of confined drug molecules is challenging, this is central to devising better ways for controlled release of therapeutic agents. Herein we demonstrate the efficacy of synchrotron microspectroscopy to track the in situ release of 5-fluorouracil (5-FU) anticancer drug molecules from a drug@MOF/polymer composite (5-FU@HKUST-1/polyurethane). Using experimental time-resolved infrared spectra jointly with newly developed density functional theory calculations, we reveal the detailed dynamics of vibrational motions underpinning the dissociation of 5-FU bound to the framework of HKUST-1 upon water exposure. We discover that HKUST-1 creates hydrophilic channels within the hydrophobic polyurethane matrix hence helping to tune drug release rate. The synergy between a hydrophilic MOF with a hydrophobic polymer can be harnessed to engineer a tunable nanocomposite that alleviates the unwanted burst effect commonly encountered in drug delivery.<br>

Download Full-text

Elucidating the Drug Release from Metal-Organic Framework Nanocomposites via in Situ Synchrotron Microspectroscopy and Theoretical Modelling

10.26434/chemrxiv.9975389.v1 ◽

2019 ◽

Author(s):

Barbara Souza ◽

Lorenzo Dona ◽

Kirill Titov ◽

Paolo Bruzzese ◽

Zhixin Zeng ◽

...

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Density Functional ◽

Metal Organic Framework ◽

Density Functional Theory Calculations ◽

Theoretical Modelling ◽

Time Resolved ◽

Drug Molecules ◽

Metal Organic

Nanocomposites comprising metal-organic frameworks (MOFs) embedded in a polymeric matrix are promising carriers for drug delivery applications. While understanding the chemical and physical transformations of MOFs during the release of confined drug molecules is challenging, this is central to devising better ways for controlled release of therapeutic agents. Herein we demonstrate the efficacy of synchrotron microspectroscopy to track the in situ release of 5-fluorouracil (5-FU) anticancer drug molecules from a drug@MOF/polymer composite (5-FU@HKUST-1/polyurethane). Using experimental time-resolved infrared spectra jointly with newly developed density functional theory calculations, we reveal the detailed dynamics of vibrational motions underpinning the dissociation of 5-FU bound to the framework of HKUST-1 upon water exposure. We discover that HKUST-1 creates hydrophilic channels within the hydrophobic polyurethane matrix hence helping to tune drug release rate. The synergy between a hydrophilic MOF with a hydrophobic polymer can be harnessed to engineer a tunable nanocomposite that alleviates the unwanted burst effect commonly encountered in drug delivery.<br>

Download Full-text

Effects of Co-Solvents on Loading and Release Properties of Self-Assembled Di-Peptide Building Blocks, towards Drug Delivery Applications

Protein and Peptide Letters ◽

10.2174/0929866528666211126160432 ◽

2021 ◽

Vol 28 ◽

Author(s):

Sara Yazdani ◽

Seyed Mohammad Ghoreishi ◽

Neda Habibi

Keyword(s):

Drug Delivery ◽

Building Blocks ◽

Amino Acid Sequences ◽

Molecular Structures ◽

Flufenamic Acid ◽

Mixture Ratio ◽

Drug Molecules ◽

Release Capacity ◽

Essential Properties ◽

Drug Delivery Applications

Background: Due to their solid-like porous structure, molecular organogel and microcrystal structures have the capabilities of loading drug molecules, encapsulation, and extended release, all considered as essential properties in drug delivery applications. Phases of these structures, however, depend on the solvent used during the gelation process. Objective: Understanding the phase transition between organogel and microcrystal structures through adjusting the mixture ratio of different co-solvents. Method: Short peptide Diphenylalanine as the gelation building block was used due to its amino acid sequences that can be exactly selected at its molecular levels. Ethanol as a polar solvent was used in combination with four other co-solvents with different polarity levels, namely Xylene, Toluene, Acetone, and Dimethyl Sulfoxide. The morphology of molecular structures of each co-solvent combination at each ratio level was examined as well as the loading and release properties for a non-polar Flufenamic Acid drug. Results: The resultant structure wasaffected by the polarity of the co-solvents; in particular, in the sample containing 25 μg/ml of the drug, 94% of the drug amount was loaded inside the organogel. By increasing the drug concentration to 50, 75, and 100 μg/ml, the loading capability decreased to 76%, 47%, and 33%, respectively. Conclusion: Molecular organogels have excellent capabilities of loading drug molecules, while microcrystal structures have higher release capacity. The findings of this study reveal how to best design a gelation method to obtain maximum loading or release properties for a particular peptide-based drug delivery application.

Download Full-text