Polyethyleneimine-mediated assembly of DNA nanotubes for KRAS siRNA delivery in lung adenocarcinoma therapy.

Self-assembled DNA nanostructures hold great promise in biosensing, drug delivery and nanomedicine. Nevertheless, challenges like instability and inefficiency in cellular uptake of DNA nanostructures under physiological conditions limit their practical use. To tackle these obstacles, this study proposes a novel approach that integrates the cationic polymer polyethyleneimine (PEI) with DNA self-assembly. The hypothesis is that the positively charged linear PEI can facilitate the self-assembly of DNA nanostructures, safeguard them against harsh conditions and impart them with the cellular penetration characteristic of PEI. As a demonstration, a DNA nanotube (PNT) was successfully synthesized through PEI mediation, and it exhibited significantly enhanced stability and cellular uptake efficiency compared to conventional Mg2+-assembled DNA nanotubes. The internalization mechanism was further found to be both clathrin-mediated and caveolin-mediated endocytosis, influenced by both PEI and DNA. To showcase the applicability of this hybrid nanostructure for biomedical settings, the KRAS siRNA-loaded PNT was efficiently delivered into lung adenocarcinoma cells, leading to excellent anticancer effects in vitro. These findings suggest that the PEI-mediated DNA assembly could become a valuable tool for future biomedical applications.

Multifunctional Droplets Formed by Interfacially Self-Assembled Fluorinated Magnetic Nanoparticles for Biocompatible Single Cell Culture and Magnet-Driven Manipulation.

The ability to encapsulate and manipulate droplets with a picoliter volume of samples and reagents shows great potential for practical applications in chemistry, biology, and materials science. Magnetic control is a promising approach for droplet manipulation due to its ability for wireless control and its ease of implementation. However, it is challenged by the poor biocompatibility of magnetic materials in aqueous droplets. Moreover, current droplet technology is problematic because of the molecule leakage between droplets. In the paper, we propose multifunctional droplets with the surface coated by a layer of fluorinated magnetic nanoparticles for magnetically actuated droplet manipulation. Multifunctional droplets show excellent biocompatibility for cell culture, nonleakage of molecules, and high response to a magnetic field. We developed a strategy of coating the F-MNP@SiO2 on the outer surface of droplets instead of adding magnetic material into droplets to enable droplets with a highly magnetic response. The encapsulated bacteria and cells in droplets did not need to directly contact with the magnetic materials at the outer surface, showing high biocompatibility with living cells. These droplets can be precisely manipulated based on magnet distance, the time duration of the magnetic field, the droplet size, and the MNP composition, which well match with theoretical analysis. The precise magnetically actuated droplet manipulation shows great potential for accurate and sensitive droplet-based bioassays like single cell analysis.

Improving Longitudinal Transversal Relaxation Of Gadolinium Chelate Using Silica Coating Magnetite Nanoparticles.

INTRODUCTION AND OBJECTIVE: Precisely and sensitively diagnosing diseases especially early and accurate tumor diagnosis in clinical magnetic resonance (MR) scanner is a highly demanding but challenging task. Gadolinium (Gd) chelate is the most common T 1 magnetic resonance imaging (MRI) contrast agent at present. However, traditional Gd-chelates are suffering from low relaxivity, which hampers its application in clinical diagnosis. Currently, the development of nano-sized Gd based T 1 contrast agent, such as incorporating gadolinium chelate into nanocarriers, is an attractive and feasible strategy to enhance the T 1 contrast capacity of Gd chelate. The objective of this study is to improve the T 1 contrast ability of Gd-chelate by synthesizing nanoparticles (NPs) for accurate and early diagnosis in clinical diseases. METHODS: Reverse microemulsion method was used to coat iron oxide (IO) with tunable silica shell and form cores of NPs IO@SiO2 at step one, then Gd-chelate was loaded on the surface of silica-coated iron oxide NPs. Finally, Gd-based silica coating magnetite NPs IO@SiO2-DTPA-Gd was developed and tested the ability to detect tumor cells on the cellular and in vivo level. RESULTS: The r 1 value of IO@SiO2-DTPA-Gd NPs with the silica shell thickness of 12 nm was about 33.6 mM-1s-1, which was approximately 6 times higher than Gd-DTPA, and based on its high T 1 contrast ability, IO@SiO2-DTPA-Gd NPs could effectively detect tumor cells on the cellular and in vivo level. CONCLUSION: Our findings revealed the improvement of T 1 relaxation was not only because of the increase of molecular tumbling time caused by the IO@SiO2 nanocarrier but also the generated magnetic field caused by the IO core. This nanostructure with high T 1 contrast ability may open a new approach to construct high-performance T 1 contrast agent.

Interfacial engineered gadolinium oxide nanoparticles for magnetic resonance imaging guided microenvironment-mediated synergetic chemodynamic/photothermal therapy.

Engineering interfacial structure of biomaterials have drawn much attention due to it can improve the diagnostic accuracy and therapy efficacy of nanomedicine, even introducing new moiety to construct theranostic agents. Nanosized magnetic resonance imaging contrast agent holds great promise for the clinical diagnosis of disease, especially tumor and brain disease. Thus, engineering its interfacial structure can form new theranostic platform to achieve effective disease diagnosis and therapy. In this study, we engineered the interfacial structure of typical MRI contrast agent, Gd2O3, to form a new theranostic agent with improved relaxivity for MRI guided synergetic chemodynamic/photothermal therapy. The synthesized Mn doped gadolinium oxide nanoplate exhibit improved T1 contrast ability due to large amount of efficient paramagnetic metal ions and synergistic enhancement caused by the exposed Mn and Gd cluster. Besides, the introduced Mn element endow this nanomedicine with the Fenton-like ability to generate OH from excess H2O2 in tumor site to achieve chemodynamic therapy (CDT). Furthermore, polydopamine engineered surface allow this nanomedicine with effective photothermal conversion ability to rise local temperature and accelerate the intratumoral Fenton process to achieve synergetic CDT/photothermal therapy (PTT). This work provides new guidance for designing magnetic resonance imaging guided synergetic CDT/PTT to achieve tumor detection and therapy.