Graphene nanoparticles for microRNA delivery

Background: Graphene (G) has been established as an exciting prospect for a broad range of applications owing to its remarkable properties. As the molecular structure of G itself is achiral thus introducing chirality in G by simple attachment of a functional group (a chiral ligand) on the G nanosheet may result in more diverse applications. The recent innovations of G chiral nanosystems have been extended to drug delivery. Herein, we have developed a novel and facile synthesis method for producing chiral G for its application in chirality-dependent microRNA delivery. Methods: L-graphene and D-graphene were produced in a single step by using chiral L-tyrosine and D-tyrosine as stabilizing and chiral-inducing agents and applying high-temperature sonication. The chirality of the exfoliated L-graphene and D-graphene was assessed with circular dichroism (CD) spectroscopy and their structural, morphological, and surface evaluations were studied using Raman spectroscopy, transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS), respectively. In addition, an attempt has been made to explore cell viability, hemocompatibility, cellular uptake, internalization pathway, chirality-mediated interaction, and microRNA (hsa-miR-205-5p) transfection with C4-2B prostate cancer cells. Results: The CD spectra confirmed the chirality present in the exfoliated L(D)-Graphene. Moreover, the Raman spectrum and TEM data confirmed the formation of multi-layer graphene with asymmetric morphology and a large aspect ratio. L-graphene and D-graphene show cellular compatibility. Chiral preferential binding occurring between miR-205 and D-graphene makes them an exciting prospect for gene delivery. D-graphene exhibits superior hemocompatibility compared to commercially available transfection reagents (Lipofectamine). Cellular uptake is clearly shown by the internalization of D-graphene into C4-2B prostate cancer cells. miR-205 efficient delivery utilizing D-graphene was confirmed by transfection efficiency and MTT assay. Conclusions: Our results demonstrated a direct approach- one-step liquid phase exfoliation-induced chirality in graphene and their selective chirality-mediated microRNA delivery

Nebulization based Inhalation Nanomedicine for Lung Cancer Treatments

Background: Lung cancer is reported to have a high incidence rate and first leading cause of cancer-related morbidity and mortality across the world including in the United States. Noninvasive nebulized inhalation is a promising delivery strategy for lung, which can enhance the targeting efficiency and detention time interval of nanoparticles in the lung tissue, thus elevating the therapeutic index of therapeutic agent(s) at lower dosages. The aim of this study is to develop inhalable nanoparticles (INPs) for effective delivery of therapeutic agents in lung cancer cell lines and ex vivo models. Methods: The inhalation nanoparticles (INPs) were prepared by solvent evaporation and self-assembly approach. The INPs formulations were characterized by particle size, chemical composition, and drug loading efficiency using various analytical methods including FT-IR, DSC, SEM, and DSC/TGA. Cellular uptake of INPs was evaluated in 2D and 3D models of lung cancer cell lines (A549 and NCI-H1299) using fluorescence microscopy and flow cytometry analysis. Additionally, the therapeutic evaluation of gambogic acid and gemcitabine encapsulated INPs was performed by basic in vitro biological assays using proliferation (CCK-8), mucoadhesion Boyden chamber, and apoptosis assays using lung cancer (A549 and NCI-H1299) monolayers, spheroids, and xenograft tumors. Results: The developed INPs exhibited an average size of ~110 nm in dynamic light scattering measurements. INPs formulation showed a remarkable mucoadhesion and mucopenetration potential in-vitro model(s). Cellular uptake studies demonstrated that INPs formulation facilitates an effective endosomal release into the cytosol. The in vitro study confirms that INPs release the drugs in a sustained manner. Additionally, the INPs formulation showed superior in vitro anti-cancer activity in lung cancer cell lines, spheroids and xenograft tumor. Conclusions: Altogether this study confirms that INPs formulation demonstrates an improved therapeutic benefit over free drug against lung cancer cell lines, spheroids and xenograft tumor. This study could lead as an innovative therapeutic modality for the treatment of lung cancer

One-step simultaneous liquid phase exfoliation-induced chirality in graphene and their chirality-mediated microRNA delivery

Background: Graphene (G) has been established as an exciting prospect for a broad range of applications owing to its remarkable properties. As the molecular structure of G itself is achiral thus introducing chirality in G by simple attachment of a functional group (a chiral ligand) on the G nanosheet may result in more diverse applications. The recent innovations of G chiral nanosystems have been extended to drug delivery. Herein, we have developed a novel and facile synthesis method for producing chiral G for its application in the chirality-dependent microRNA delivery. Methods: L-graphene and D-graphene were produced in a single step by using chiral L-tyrosine and D-tyrosine as a stabilizing and chiral-inducing agent and applying high-temperature sonication. The chirality of the exfoliated L-graphene and D-graphene was assessed with circular dichroism (CD) spectroscopy and their structural, morphological, and surface evaluations were studied using Raman spectroscopy, transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS), respectively. In addition, an attempt has been made to explore the cell viability, hemocompatibility, cellular uptake, and internalization pathway, chirality-mediated interaction, and microRNA (hsa-miR-205-5p) transfection with C4-2B prostate cancer cells. Results: The CD spectra confirmed the chirality present in the exfoliated L(D)-Graphene. Moreover, the Raman spectrum and TEM data confirmed the formation of multi-layer graphene with asymmetric morphology and a large aspect ratio. L-graphene and D-graphene show cellular compatibility. Chiral preferential binding occurring between miR-205 and D-graphene makes them an exciting prospect for gene delivery. D-graphene exhibits superior hemocompatibility compared to commercially available transfection reagent (Lipofectamine). Cellular uptake is clearly shown by internalization of D-graphene into C4-2B prostate cancer cells. miR-205 efficient delivery utilizing D-graphene was confirmed by transfection efficiency and MTT assay. Conclusions: Our results demonstrated that a direct approach- one-step liquid phase exfoliation-induced chirality in graphene and their selective chirality-mediated microRNA delivery

Development of liposomes using microfluids for delivery of miR-205

Background: The therapeutic application of microRNA(s) in the field of cancer has generated significant attention in research. miR-205 is a tumor suppressor in various cancers. However, the delivery of miR-205 is an unmet clinical need. Thus, the development of liposomal formulation platform to deliver miR-205 is highly sought. The most common applications of liposome formulations are vaccines and anticancer formulations (e.g., mRNA, small molecule drugs). However, large-scale production with precise control of size and size distribution of the lipid-based drug delivery systems (DDSs) is one of the major challenges in the pharmaceutical industry. The objective of this study is to develop liposomal formulation with precise size and optimal for delivery of miR-205. Methods: Microfluidics chip designed based on commercial microfluidic device platform was employed for preparation of liposomes. The device is set for the synthesis of liposome at total flow rate (FRR) 10 ml min−1 and 1:3 flow rate ratio (TFR). To determine the optimal conditions, the effect of different factors including FRR, TFR, and total lipid concentration (lipid and cholesterol) on particle size and size distribution is investigated. Liposomes are also produced by a bulk method to compare the properties of the liposomes formed through these methods. The obtained formulations were tested to analyses different physiochemical properties (DLS, FTIR, DSC, and TGA), stability studies and optimized liposomal formulation was confirmed by examining the intracellular accumulation. Results: All formulations displayed an average size less than 200 nm and exhibited acceptable physicochemical behavior. This design demonstrated high productivity and better control of liposome size and polydispersity index (PDI) than conventional liposome preparation methods. The microfluidic devices were used to produce miR-205-loaded liposomes under different processing conditions which were later characterized and studied in vitro to evaluate their efficiency as a drug delivery system. Conclusions: The obtained results demonstrated that the liposomes can effectively deliver miR-205 into cancer cells. Therefore, the microfluidic devices platform are promising devices for reproducible and scalable manufacturing of liposomal formulation

Therapeutics to tackle Omicron outbreak

In this commentary, the authors have focused on the mutational impact of the Omicron variant on the current therapeutics to manage #COVID19