Biocompatibility and cytotoxicity in vitro of surface-functionalized drug-loaded spinel ferrite nanoparticles

In this study, poly(isobutylene-alt-maleic anhydride) (PMA)-coated spinel ferrite (MFe2O4, where M = Fe, Co, Ni, or Zn) nanoparticles (NPs) were developed as carriers of the anticancer drugs doxorubicin (DOX) and methotrexate (MTX). Physical characterizations confirmed the formation of pure cubic structures (14–22 nm) with magnetic properties. Drug-loaded NPs exhibited tumor specificity with significantly higher (p < 0.005) drug release in an acidic environment (pH 5.5). The nanoparticles were highly colloidal (zeta potential = −35 to −26 mV) in deionized water, phosphate buffer saline (PBS), and sodium borate buffer (SBB). They showed elevated and dose-dependent cytotoxicity in vitro compared to free drug controls. The IC50 values ranged from 0.81 to 3.97 μg/mL for HepG2 and HT144 cells, whereas IC50 values for normal lymphocytes were 10 to 35 times higher (18.35–43.04 µg/mL). Cobalt ferrite (CFO) and zinc ferrite (ZFO) NPs were highly genotoxic (p < 0.05) in cancer cell lines. The nanoparticles caused cytotoxicity via oxidative stress, causing DNA damage and activation of p53-mediated cell cycle arrest (significantly elevated expression, p < 0.005, majorly G1 and G2/M arrest) and apoptosis. Cytotoxicity testing in 3D spheroids showed significant (p < 0.05) reduction in spheroid diameter and up to 74 ± 8.9% of cell death after two weeks. In addition, they also inhibited multidrug resistance (MDR) pump activity in both cell lines suggesting effectivity in MDR cancers. Among the tested MFe2O4 NPs, CFO nanocarriers were the most favorable for targeted cancer therapy due to excellent magnetic, colloidal, cytotoxic, and biocompatible aspects. However, detailed mechanistic, in vivo cytotoxicity, and magnetic-field-assisted studies are required to fully exploit these nanocarriers in therapeutic applications.

A nontoxic ionic liquid composition for the delivery of biological macromolecular anions across the skin barrier

The development of biocompatible ionic liquids is needed in order to explore their vastly underutilized pharmaceutical potential. US10912834 patent discloses ionic liquids comprising macromolecular biological anions and alkylated cations, which provides enhanced dermal delivery and cell internalization of the large biological anions. The studies of ex vivo permeation through excised pig skin indicated significantly higher skin penetration of percent dose and enhanced drug internalization was achieved using these ionic liquids. Although, the patent advances an infant field of biological macromolecule-based ionic liquids, the evaluation of these claimed ionic liquids relies only on the in vivo cytotoxicity data and ex vivo skin permeation behavior. Exhaustive studies, including dermatokinetic evaluation and long-term animal toxicity experiments, should be performed in order to unravel the potential of the aforementioned ionic liquids.

Advanced Functional Materials Based on Nanocellulose for Pharmaceutical/Medical Applications

Nanocelluloses (NCs), with their remarkable characteristics, have proven to be one of the most promising “green” materials of our times and have received special attention from researchers in nanomaterials. A diversity of new functional materials with a wide range of biomedical applications has been designed based on the most desirable properties of NCs, such as biocompatibility, biodegradability, and their special physicochemical properties. In this context and under the pressure of rapid development of this field, it is imperative to synthesize the successes and the new requirements in a comprehensive review. The first part of this work provides a brief review of the characteristics of the NCs (cellulose nanocrystals—CNC, cellulose nanofibrils—CNF, and bacterial nanocellulose—BNC), as well as of the main functional materials based on NCs (hydrogels, nanogels, and nanocomposites). The second part presents an extensive review of research over the past five years on promising pharmaceutical and medical applications of nanocellulose-based materials, which have been discussed in three important areas: drug-delivery systems, materials for wound-healing applications, as well as tissue engineering. Finally, an in-depth assessment of the in vitro and in vivo cytotoxicity of NCs-based materials, as well as the challenges related to their biodegradability, is performed.

A Novel off-the-Shelf Trastuzumab-Armed NK Cell Therapy (ACE1702) Using Antibody-Cell-Conjugation Technology

Natural killer (NK) cells harbor efficient cytotoxicity against tumor cells without causing life-threatening cytokine release syndrome (CRS) or graft-versus-host disease (GvHD). When compared to chimeric antigen receptor (CAR) technology, Antibody-Cell Conjugation (ACC) technology has been developed to provide an efficient platform to arm immune cells with cancer-targeting antibodies to recognize and attack cancer cells. Recently, we established an endogenous CD16-expressing oNK cell line (oNK) with a favorable expression pattern of NK activation/inhibitory receptors. In this study, we applied ACC platform to conjugate oNK with trastuzumab and an anti-human epidermal growth factor receptor 2 (HER2) antibody. Trastuzumab-conjugated oNK, ACE-oNK-HER2, executed in vitro and in vivo cytotoxicity against HER2-expressing cancer cells and showed enhanced T cell-recruiting capability and secretion of IFNγ. The irradiated and cryopreserved ACE-oNK-HER2, designated as ACE1702, retained superior HER2-specific in vitro and in vivo potency with no tumorigenic potential. In conclusion, this study provides the evidence to support the potential clinical application of ACE1702 as a novel off-the-shelf NK cell therapy against HER2-expressing solid tumors.

Repurposing celecoxib analogues as leads for antibiotics

There is an urgent need for new antibiotics and alternative strategies to combat bacterial pathogens. Molecular docking, antibacterial evaluation in vitro and in vivo, cytotoxicity assessment and enzyme inhibition analyses were performed. Compound 12 exhibited antimicrobial activity against Staphylococcus aureus (MIC: 4 μg/ml), various clinically isolated strains of MRSA (MIC: 4–16 μg/ml) and Acinetobacter baumannii (MIC: 4 μg/ml) when combined with subinhibitory concentrations of colistin B. Compound 12 (20 mg/kg) yielded mild improvement in survival of methicillin-resistant Staphylococcus aureus (MRSA)-infected mice. Additionally, enzyme inhibition tests showed that compound 12 exhibited inhibitory effects against S. aureus dihydrofolate reductase (105.1 μg/ml) and DNA gyrase (122.8 μg/ml). Compound 12 is a promising antibacterial candidate for further development.

Facile Preparation of Liposomes-encapsulated Zn-DTPA from Soy Lecithin for Decorporation of Radioactive Actinides

Diethylenetriaminepentaacetic acid (DTPA) is an attractive decorporation agent that can enhance the excretion of radioactive actinides such as plutonium, americium, and curium after a radiological incident. However, DTPA is excreted in a short period of time after administration. Several formulations have been developed to improve DTPA pharmacokinetic properties. In this project, liposomes were prepared facilely from soy lecithin as a nanocarrier for pulmonary delivery of Zn-DTPA. Lipid hydration, reverse phase evaporation, and mechanical sonication were three methods evaluated for the preparation of liposomes-encapsulated Zn-DTPA. Mechanical sonication was the method of choice due to simple apparatus and facile preparation. Liposomes-encapsulated Zn-DTPA (lipo-Zn-DTPA) exhibited a hydrodynamic diameter of 178(±2) nm and a spherical shape. The loading capacity and encapsulation efficiency of Zn-DTPA were 41(±5) mg/g and 10(±1)%, respectively. Lyophilization of lipo-Zn-DTPA for extended storage did not affect the amount of encapsulated drug or damage the structure of liposomes. An in vivo cytotoxicity test confirmed no serious adverse effect of Zn-DTPA encapsulated lecithin liposomes in rats.