730 nm Light-Induced Cleavage of BODIPY Photocages via Entropy-Driven Triplet Sensitization

Light-activated drug delivery systems allow precise spatiotemporal control of a drug release process. However, safe and efficient drug release activation needs a low-power nonpulsed red/near-infrared light with high tissue penetration depth. Nevertheless, such systems remain a challenge. Herein, a self-assembled nanovehicle made of 2,6-diiodo-B-dimethyl-boron dipyrromethene (BODIPY)-based photocleavable trigonal molecules bearing Pt(II) meso-tetraphenyltetranaphthoporhyrin photosensitizer and a fluorescent release marker Nile Red in hydrophobic core is introduced. The system employs endothermic triplet–triplet energy transfer between the photosensitizer and the trigonal molecule, leading to the cleavage of the trigonal molecule followed by cargo release. This allows to engage 730 nm light to cleave BODIPY photoremovable protecting groups (PPGs) instead of 530 nm light that would be needed for direct photocage excitation. Therefore, the approach unleashes the desired activation of drug release via photocleavage with longer wavelengths (within the phototherapeutic window) without any chemical modification of the PPGs. Cell studies demonstrate fast intracellular uptake of the nanovehices by PC3 human prostate cancer cells with accumulation in lysosomes in 2 h. Light irradiation at 730 nm on nanovehicles dispersed in cell media leads to payload release. Remarkably, the system exhibits higher release efficiency at low oxygen concentration than at ambient thus allowing to tackle aggressive hypoxic solid tumors.Peer reviewe

Correction: Printed, cost-effective and stable poly(3-hexylthiophene) electrolyte-gated field-effect transistors

Correction for 'Printed, cost-effective and stable poly(3-hexylthiophene) electrolyte-gated field-effect transistors' by Davide Blasi et al., J. Mater. Chem. C, 2020, DOI: 10.1039/d0tc03342a

In Situ Coupled Electrochemical-Goniometry as a Tool to Reveal Conformational Changes of Charged Peptides

The opportunity to manipulate cell functions by regulating bioactive surfaces is a potentially promising approach for organic bioelectronics. Here, the tuning of the orientation of charged peptides by means of an electrical input observed via optical tensiometry is reported. A stimuli-responsive self-assembled monolayer (SAM) with specially designed charged peptides is used as a model system to switch between two separate hydrophilic states. The underwater contact angle (UCA) technique is used to measure changes in the wetting property of a dichloromethane droplet under electrical stimuli. The observed changes in the UCA of the bio-interface can be understood in terms of a change in the surface energy between the ON and OFF states. Molecular dynamics simulations in an electric field have been performed to verify the hypothesis of the orientational change of the charged peptides upon electrical stimulation. In addition, X-ray photoelectron spectroscopy (XPS) is performed to clarify the stability of the functionalized electrodes. Finally, the possibility of using such a novel switching system as a tool to characterize bioactive surfaces is discussed

Injectable and printable nanocellulose-crosslinked quaternary chitosan blends for potential wound healing

Developing hydrogels with excellent 3D printability, injectability, and mechanical integrity presents an imposing challenge in biomaterials research, especially in the biomedical field where biocompatibility is crucial. This study involved the development of 3D printable and injectable polysaccharide-based hydrogels with inherent self-healing capabilities. Carboxymethyl chitosan and quaternized chitosan (QCS) functioned as polymer backbones, reinforced by dialdehyde-cellulose nanocrystals (DACNC) as a cross-linker. Here, the concentrations of QCS and DACNC were adjusted and optimized for ideal performance. The cross-linking process was orchestrated in situ, integrating dynamic hydrogen bonds and Schiff base covalent bonds to achieve a multi-cross-linked hydrogel network. Comprehensive characterization of the material, including rheological measurements and macroscopic evaluations, demonstrated the hydrogel’s admirable injectability, printability, and self-healing attributes. In vitro cell viability assessments on human dermal fibroblasts revealed favorable biocompatibility and minimal cytotoxicity of the hydrogels, properties influenced by the concentrations of QCS. The obtained hydrogels exhibit promising attributes suitable for fabricating 3D printable and injectable hydrogel customized for biomedical applications, particularly wound healing. Graphical abstract: (Figure presented.)Peer reviewe

Development of Robust Cationic Light-Activated Thermosensitive Liposomes : Choosing the Right Lipids

Extensive research has been conducted on cationic light-activated thermosensitive liposomes (CLTSLs) as a means for site-specific and controlled drug release; however, less attention has been given to the stability of these nanoparticles. Selecting the appropriate lipids is crucial for the development of a stable and responsive system. In this study, we investigated the impact of various lipids on the physical properties of cationic light-activated liposomes. Incorporating poly(ethylene glycol) PEG molecules resulted in uniform liposomes with low polydispersity index, while the addition of unsaturated lipid (DOTAP) resulted in extremely leaky liposomes, with almost 80% release in just 10 min of incubation at body temperature. Conversely, the inclusion of cholesterol in the formulation increased liposome stability too much and decreased their sensitivity to stimuli-responsive release, with only 14% release after 2 min of light exposure. To achieve stable and functional CLTSL, we substituted an equivalent amount of unsaturated lipid with a saturated lipid (DPTAP), resulting in stable liposomes at body temperature that were highly responsive to light, releasing 90% of their content in 10 s of light exposure. We also conducted two atomistic molecular dynamics simulations using lipid compositions with saturated and unsaturated lipids to investigate the effect of lipid composition on the dynamical properties of the liposomal lipid bilayer. Our findings suggest that the nature of lipids used to prepare liposomes significantly affects their properties, especially when the drug loading needs to be stable but triggered drug release properties are required at the same time. Selecting the appropriate lipids in the right amount is therefore essential for the preparation of liposomes with desirable properties.Peer reviewe

Surface Plasmon Resonance Assay for Label-Free and Selective Detection of HIV-1 p24 Protein

The early detection of the human immunodeficiency virus (HIV) is of paramount importance to achieve efficient therapeutic treatment and limit the disease spreading. In this perspective, the assessment of biosensing assay for the HIV-1 p24 capsid protein plays a pivotal role in the timely and selective detection of HIV infections. In this study, multi-parameter-SPR has been used to develop a reliable and label-free detection method for HIV-1 p24 protein. Remarkably, both physical and chemical immobilization of mouse monoclonal antibodies against HIV-1 p24 on the SPR gold detecting surface have been characterized for the first time. The two immobilization techniques returned a capturing antibody surface coverage as high as (7.5 +/- 0.3) x 10(11) molecule/cm(2) and (2.4 +/- 0.6) x 10(11) molecule/cm(2), respectively. However, the covalent binding of the capturing antibodies through a mixed self-assembled monolayer (SAM) of alkanethiols led to a doubling of the p24 binding signal. Moreover, from the modeling of the dose-response curve, an equilibrium dissociation constant K-D of 5.30 x 10(-9) M was computed for the assay performed on the SAM modified surface compared to a much larger K-D of 7.46 x 10(-5) M extracted for the physisorbed antibodies. The chemically modified system was also characterized in terms of sensitivity and selectivity, reaching a limit of detection of (4.1 +/- 0.5) nM and an unprecedented selectivity ratio of 0.02

Label-free electronic detection of peptide post-translational modification with functional enzyme-driven assay at the physical limit

High-performance, ultra-sensitive, and universal protein post-translational modification (PTM) and protein-protein interaction (PPI) technologies are eagerly pursued in the pharmaceutical industry and bioanalytical research. Novel PTM and PPI detection methods outperform traditional assays in scope and scalability, enabling the collection of information on multiple biochemical targets. Detecting peptides and proteins at the single-molecule level is done by utilizing nanosized transducing elements and assaying solutions at very high analyte concentrations, in the nanomolar range or higher. Here, a proof of principle of a biosensing platform for single-molecule PTM detection is demonstrated. This platform is based on the single molecule with a large transistor (SiMoT) technology, encompassing a millimeter-sized electrolyte-gated organic field-effect transistor, for label-free PTM detection with a zeptomolar limit of detection. Sensitivity is improved 106- to 1012-fold compared with mass-spectrometry and luminescence-based assay methods. A functional assay for detecting enzyme-driven peptide PTMs in the zeptomolar concentration range is demonstrated using multivariate data processing, opening the way for future applications to monitor PTMs

Delivery of gene editing therapeutics

For the past decades, gene editing demonstrated the potential to attenuate each of the root causes of genetic, infectious, immune, cancerous, and degenerative disorders. More recently, Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated protein 9 (CRISPR-Cas9) editing proved effective for editing genomic, cancerous, or microbial DNA to limit disease onset or spread. However, the strategies to deliver CRISPR-Cas9 cargos and elicit protective immune responses requires safe delivery to disease targeted cells and tissues. While viral vector-based systems and viral particles demonstrate high efficiency and stable transgene expression, each are limited in their packaging capacities and secondary untoward immune responses. In contrast, the nonviral vector lipid nanoparticles were successfully used for as vaccine and therapeutic deliverables. Herein, we highlight each available gene delivery systems for treating and preventing a broad range of infectious, inflammatory, genetic, and degenerative diseases. Statement of significance: CRISPR-Cas9 gene editing for disease treatment and prevention is an emerging field that can change the outcome of many chronic debilitating disorders.</p