A self-assembled DNA nanostructure for targeted and pH-triggered drug delivery to combat doxorubicin resistance

2016 ◽  
Vol 4 (22) ◽  
pp. 3854-3858 ◽  
Author(s):  
Juan Liu ◽  
Xiaowei Ma ◽  
Chunni Lei ◽  
Xiangdong Xue ◽  
Tuo Wei ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Cells ◽  
The Self ◽  
Doxorubicin Resistance ◽  
Dna Nanostructure ◽  
Self Assembled ◽  
Target Cancer

The self-assembled DNA nanostructure was able to specifically target cancer cells and release the drug at pH 5.0.

Electrostatic Self-Assembly of Functionalized Nanodiamonds and Their Binding Capacity With Doxorubicin Drugs

2010 ◽  
Author(s):  
Ashfaq Adnan ◽  
Wing Kam Liu
Keyword(s):  
Drug Release ◽  
Cancer Cells ◽  
Functional Groups ◽  
Drug Absorption ◽  
Self Assembly ◽  
The Self ◽  
Adsorption And Desorption ◽  
Drug Adsorption ◽  
Drug Molecules ◽  
Self Assembled

While cancers have no known cure, some of them can be successfully treated with the combination of surgery and systematic therapy. In general, systemic/widespread chemotherapy is usually injected into the bloodstream to attempt to target cancer cells. Such procedure often imparts devastating side effects because cancer drugs are nonspecific in activity, and transporting them throughout the bloodstream further reduces their ability to target the right region. This means that they kill both healthy and unhealthy cells. It has been observed that the physiological conditions of the fluids around living cells can be characterized by pH, and the magnitude of pH around a living cell is different from cancerous cells. Moreover, a multiscale anatomy of carcinoma will reveal that the microstructure of cancer cells contains some characteristic elements such as specific biomarker receptors and DNA molecules that exclusively differentiate them from healthy cells. If these cancer specific ligands can be intercalated by some functional molecules supplied from an implantable patch, then the patch can be envisioned to serve as a complementary technology with current systemic therapy to enhance localized treatment efficiency, minimize excess injections/surgeries, and prevent tumor recurrence. The broader objective of our current research is to capture some fundamental insights of such drug delivery patch system. It is envisioned that the essential components of the device is nanodiamonds (ND), parylene buffer layer and doxorubicin (DOX) drugs. In its simplest form, self-assembled nanodiamonds - functionalized or pristine, and DOX molecules are contained inside parylene capsule. The efficient functioning of the device is characterized by its ability to precisely detect targets (cancer cells) and then to release drugs at a controlled manner. The fundamental science issues concerning the development of the ND-based device include: 1. A precise identification of the equilibrium structure and self assembled morphology of nanodiamonds, 2. Fundamental understanding of the drug adsorption and desorption process to and from NDs, and 3. The rate of drug release through the parylene buffers. The structure of the nanodiamond (ND) is crucial to the adsorption and desorption of drug molecules because it not only changes the self-assembly configuration but also alters the surface electrostatics. To date, the structure and electrostatics of NDs are not yet well understood. A density functional tight binding theory (DFTB) study on smaller [2] NDs suggests a facet dependent charge distributions on ND surfaces. These charges are estimated by Mulliken Analysis [1]. Using the charges for smaller NDs (∼valid for 1–3.3 nm dia ND) we first projected surface charges for larger (4–10 nm) truncated octahedral nanodiamonds (TOND), and it has been found that the [100] face and the [111] face contain positively and negatively charged atoms, respectively. These projected charges are then utilized to obtain the self assembled structure of pristine TONDs from Molecular Dynamics (MD) simulations [4] as shown in Fig. 1. The opposite charges on the [100] and [111] face invoked electrostatic attractions among the initially isolated NDs and a network of nanodiamond agglutinates are formed as evidenced in Fig. 1(b). This study confirms why as manufactured NDs are found in agglomerated form. The study also suggests that a large fraction of ND surfaces become unavailable for drug absorption as many of the [100] faces are coherently connected to [111] faces. As a result, it can be perceived that effective area for drug adsorption on ND surfaces will be less compared to theoretical prediction which suggests that a 4nm TOND may contain as high 360 drug molecules on its surface [5]. It has been observed that as manufactured NDs may contain a variety of functional groups, and currently, we are studying the mechanism of self-assembly for functionalized nanodiamonds so that we understand the role of functional groups. The next phase of calculation involves binding of the DOX to the NDs. Essentially, the understanding of drug absorption and desorption profile at a controlled rate to and from NDs is the most critical part of the device design. Some recent quantum calculation suggests that part of NDs and drug molecules contain opposite charges at their surfaces; it has been a natural interpretation that interactions between ND and drug molecules should be straight-forward — NDs should attract to drugs as soon as they come closure. Recent experiments [6], however, suggest that NDs usually do not interact with drug molecules in the presence of neutral solutions. Addition of NaCl in the solution improves the interaction dramatically. In the first part of the study, we [3–5] have studied the interaction of single DOX molecules with TOND surfaces via MD simulation. As shown in Fig. 2, this study suggests that DOX molecules first arrange them around the preferential sites on nanodiamonds (e.g. around the [111] face) and then spontaneously attach on the surface. It is also observed that only DOX molecule is attached per facets of TONDs. It can be noted that each TOND has 6 [100] face and 8 [111] faces. Figure 3 shows the energy minimization process during the DOX-ND interaction. It can be noted that these simulations have been performed in vacuum environment. In order to see how DOX interacts in solution media, another set of simulations have been conducted where “vacuum” environment have been replaced with solution media of different pH. Moreover, functionalization on the ND surfaces will create a different environment for the DOX molecules. Research is underway to capture the fundamental physics on the DOX loading and release to and from functionalized nanodiamonds. Once we understand the essential physics of drug loading and unloading, in the future we plan to model diffusion controlled drug release through ND coated film device by incorporating the multiscale science learned from the current study. Results from this study will provide fundamental insight on the definitive targeting of infected cells and high resolution controlling of drug molecules.

scholarly journals Self-assembled pH-responsive supramolecular hydrogel for hydrophobic drug delivery

RSC Advances ◽  
2018 ◽  
Vol 8 (55) ◽  
pp. 31581-31587 ◽  
Author(s):  
Lin Wang ◽  
Xuefeng Shi ◽  
Jian Zhang ◽  
Yuejun Zhu ◽  
Jinben Wang
Keyword(s):  
Drug Delivery ◽  
Cancer Cells ◽  
Drug Delivery System ◽  
Delivery System ◽  
Hydrophobic Drug ◽  
Ph Responsive ◽  
Supramolecular Hydrogel ◽  
Self Assembled

Supramolecular hydrogel, AGC16/NTS, was used to encapsulate hydrophobic drug curcumin (Cur), constructing a pH-responsive drug delivery system; the uptake of released Cur by cancer cells also occurred.

scholarly journals Tuning the Hydrophobicity of a Hydrogel Using Self-Assembled Domains of Polymer Cross-Linkers

Materials ◽  
2019 ◽  
Vol 12 (10) ◽  
pp. 1635 ◽  
Author(s):  
Hee-Jin Kim ◽  
Sungwoo Cho ◽  
Seung Joo Oh ◽  
Sung Gyu Shin ◽  
Hee Wook Ryu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Fluorescence Analysis ◽  
Building Blocks ◽  
The Self ◽  
Cell Therapies ◽  
Hydrophobically Modified ◽  
3D Matrix ◽  
Self Assembled ◽  
Cellular Microenvironments ◽  
Irregular Arrangement

Hydrogels incorporated with hydrophobic motifs have received considerable attention to recapitulate the cellular microenvironments, specifically for the bio-mineralization of a 3D matrix. Introduction of hydrophobic molecules into a hydrogel often results in irregular arrangement of the motifs, and further phase separation of hydrophobic domains, but limited efforts have been made to resolve this challenge in developing the hydrophobically-modified hydrogel. Therefore, this study presents an advanced integrative strategy to incorporate hydrophobic domains regularly in a hydrogel using self-assembled domains formed with polymer cross-linkers, building blocks of a hydrogel. Self-assemblies formed by polymer cross-linkers were examined as micro-domains to incorporate hydrophobic motifs in a hydrogel. The self-assembled structures in a pre-gelled solution were confirmed with the fluorescence analysis and the hydrophobicity of a hydrogel could be tuned by incorporating the hydrophobic chains in a controlled manner. Overall, the results of this study would greatly serve to tuning performance of a wide array of hydrophobically-modified hydrogels in drug delivery, cell therapies and tissue engineering.

scholarly journals Facile One-Pot Synthesis of Self-Assembled Folate-Biotin-Pullulan Nanoparticles for Targeted Intracellular Anticancer Drug Delivery

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Ming Wang ◽  
Meiling Huang ◽  
Jianting Wang ◽  
Mingquan Ye ◽  
Yan Deng ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Drug ◽  
Folate Receptor ◽  
Flow Cytometric Analysis ◽  
Laser Scanning Microscopy ◽  
The Self ◽  
Kb Cells ◽  
One Pot ◽  
One Pot Synthesis ◽  
Self Assembled

The self-assembled folate-biotin-pullulan (FBP) nanoparticles (NPs) were prepared by facile one-pot synthesis and their physicochemical properties were characterized. The self-assembled FBP NPs were used as an anticancer drug nanocarrier entrapping doxorubicin (DOX) for targeting folate-receptors-overexpressing cancer cells. The identification of prepared NPs to folate-receptor-expressing cancer cells (KB cells) was affirmed by cell viability measurement, folate competition test, and flow cytometric analysis. Compared with the naked DOX and DOX/BP NPs, the DOX/FBP NPs had lower IC50value compared to KB cells as a result of the folate-receptor-mediated endocytosis process. The cytotoxicity of DOX/FBP NPs to KB cells could be inhibited competitively by free folate. The cellular intake pattern of naked DOX and drug-loaded NPs was identified by confocal laser scanning microscopy (CLSM) observation and the higher cellular uptake of drug for DOX/FBP NPs over naked DOX was observed. The prepared FBP NPs had the potential to be used as a powerful carrier to target anticancer drugs to folate-receptor-expressing tumor cells and reduce cytotoxicity to normal tissues.

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

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
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.

In situ self-assembled Ag–Fe3O4 nanoclusters in exosomes for cancer diagnosis

2020 ◽  
Vol 8 (14) ◽  
pp. 2845-2855 ◽  
Author(s):  
Tayyaba ◽  
Fawad Ur Rehman ◽  
Sana Shaikh ◽  
Tanziela ◽  
Farouk Semcheddine ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Cancer Cells ◽  
Fluorescence Imaging ◽  
Cancer Diagnosis ◽  
The Self ◽  
Self Assembled

We have utilized HepG2 cancer cells for the in situ biosynthesis of silver and iron oxide nanoclusters. The self-assembled nanoclusters loaded on exosomes could be utilized to bioimage cancer through fluorescence imaging.

scholarly journals Efficient pH Dependent Drug Delivery to Target Cancer Cells by Gold Nanoparticles Capped with Carboxymethyl Chitosan

2014 ◽  
Vol 15 (5) ◽  
pp. 8216-8234 ◽  
Author(s):  
Alle Madhusudhan ◽  
Gangapuram Reddy ◽  
Maragoni Venkatesham ◽  
Guttena Veerabhadram ◽  
Dudde Kumar ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Gold Nanoparticles ◽  
Cancer Cells ◽  
Carboxymethyl Chitosan ◽  
Ph Dependent ◽  
Target Cancer
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