T Cell and Natural Killer Cell Membrane-Camouflaged Nanoparticles for Cancer and Viral Therapies.

Extensive research has been conducted on the application of nanoparticles in the treatment of cancer and infectious diseases. Due to their exceptional characteristics and flexible structure, they are classified as highly efficient drug delivery systems, ensuring both safety and targeted delivery. Nevertheless, nanoparticles still encounter obstacles, such as biological instability, absence of selectivity, recognition as unfamiliar elements, and quick elimination, which restrict their remedial capacity. To surmount these drawbacks, biomimetic nanotechnology has been developed that utilizes T cell and natural killer (NK) cell membrane-encased nanoparticles as sophisticated methods of administering drugs. These nanoparticles can extend the duration of drug circulation and avoid immune system clearance. During the membrane extraction and coating procedure, the surface proteins of immunological cells are transferred to the biomimetic nanoparticles. Such proteins present on the surface of cells confer several benefits to nanoparticles, including prolonged circulation, enhanced targeting, controlled release, specific cellular contact, and reduced in vivo toxicity. This review focuses on biomimetic nanosystems that are derived from the membranes of T cells and NK cells and their comprehensive extraction procedure, manufacture, and applications in cancer treatment and viral infections. Furthermore, potential applications, prospects, and existing challenges in their medical implementation are highlighted.

Localised polymerisation of acrylamide using single-barrel scanning electrochemical cell microscopy.

Single-barrel scanning electrochemical cell microscopy has been adapted for polymerisation of acrylamide in droplet cells formed at gold electrode surfaces. Localised electrochemical atom transfer radical polymerisation enables controlled synthesis and deposition of polyacrylamide or synthesis of polyacrylamide brushes from initiator-functionalised electrode surfaces.

Enzyme-responsive biomimetic solid lipid nanoparticles for antibiotic delivery against hyaluronidase-secreting bacteria.

In this work, a potent hyaluronidase inhibitor (ascorbyl stearate (AS)) was successfully employed to design vancomycin-loaded solid lipid nanoparticles (VCM-AS-SLNs) with biomimetic and enzyme-responsive features, to enhance the antibacterial efficacy of vancomycin against bacterial-induced sepsis. The VCM-AS-SLNs prepared were biocompatible and had appropriate physicochemical parameters. The VCM-AS-SLNs showed an excellent binding affinity to the bacterial lipase. The in vitro drug release study showed that the release of the loaded vancomycin was significantly accelerated by the bacterial lipase. The in silico simulations and MST studies confirmed the strong binding affinity of AS and VCM-AS-SLNs to bacterial hyaluronidase compared to its natural substrate. This binding superiority indicates that AS and VCM-AS-SLNs could competitively inhibit the effect of hyaluronidase enzyme, and thus block its virulence action. This hypothesis was further confirmed using the hyaluronidase inhibition assay. The in vitro antibacterial studies against sensitive and resistant Staphylococcus aureus revealed that the VCM-AS-SLNs had a 2-fold lower minimum inhibitory concentration, and a 5-fold MRSA biofilm elimination compared to the free vancomycin. Furthermore, the bactericidal-kinetic showed a 100% bacterial clearance rate within 12 h of treatment with VCM-AS-SLNs, and <50 % eradication after 24 h for the bare VCM. Therefore, the VCM-AS-SLN shows potential as an innovative multi-functional nanosystem for effective and targeted delivery of antibiotics.

Engineering hybrid nanosystems for efficient and targeted delivery against bacterial infections.

Hybrid nanoparticles (NPs) are emerging as superior alternatives to conventional nanocarriers for enhancing the delivery of antibiotics and improving their targeting at the infection site, resulting in the eradication of bacterial infections and overcoming antimicrobial resistance. They can specifically control the release of antibiotics when reaching the targeted site of infection, thus enhancing and prolonging their antimicrobial efficacy. In this review, we provide a comprehensive and an up-to-date overview of the recent advances and contributions of lipid-polymer hybrid NPs; organic-inorganic hybrid NPs; metal-organic frameworks; cell membrane-coated hybrid NPs; hybrid NP-hydrogels; and various others, that have been reported in the literature for antibacterial delivery, with emphasis on their design approaches; the nanomaterials constructed; the mechanisms of drug release; and the enhanced antibacterial efficacy of the reported hybrid nanocarriers. This review also highlights future strategies that can be used to improve the potential of hybrid nanosystems to treat bacterial infections and overcome antibiotic resistance.

Dual acting acid-cleavable self-assembling prodrug from hyaluronic acid and ciprofloxacin: A potential system for simultaneously targeting bacterial infections and cancer.

The incidence and of bacterial infections, and resulting mortality, among cancer patients is growing dramatically, worldwide. Several therapeutics have been reported to have dual anticancer and antibacterial activity. However, there is still an urgent need to develop new drug delivery strategies to improve their clinical efficacy. Therefore, this study aimed to develop a novel acid cleavable prodrug (HA-Cip) from ciprofloxacin and hyaluronic acid to simultaneously enhance the anticancer and antibacterial properties of Cip as a superior drug delivery system. HA-Cip was synthesised and characterised (FT-IR, HR-MS, and H1 NMR). HA-Cip generated stable micelles with an average particle size, poly dispersion index (PDI) and zeta potential (ZP) of 237.89 ± 25.74 nm, 0.265 ± 0.013, and -17.82 ± 1.53 mV, respectively. HA-Cip showed ≥80 % cell viability against human embryonic kidney 293 cells (non-cancerous cells), ˂0.3 % haemolysis; and a faster pH-responsive ciprofloxacin release at pH 6.0. HA-Cip showed a 5.4-fold improvement in ciprofloxacin in vitro anticancer activity against hepatocellular cancer (HepG2) cells; and enhanced in vitro antibacterial activity against Escherichia coli and Klebsiella pneumoniae at pH 6.0. Our findings show HA-Cip as a promising prodrug for targeted delivery of ciprofloxacin to efficiently treat bacterial infections associated, and/or co-existing, with cancer.

Exploring the applications of hyaluronic acid-based nanoparticles for diagnosis and treatment of bacterial infections.

Hyaluronic acid (HA) has become a topic of significant interest in drug delivery research due to its excellent properties, including biosafety, biodegradability, and nonimmunogenicity. Moreover, due to its ease of modification, HA can be used to prepare several HA-based nanosystems using various approaches. These approaches involve conjugating/grafting of hydrophobic moieties, polyelectrolytes complexation with cationic polymers, or surface modification of various nanoparticles using HA. These nanoparticles are able to selectively deliver antibacterial drugs or diagnostic molecules into the site of infections. In addition, HA can bind with overexpressed cluster of differentiation 44 (CD44) receptors in macrophages and also can be degraded by a family of enzymes called hyaluronidase (HAase) to release drugs or molecules. By binding with these receptors or being degraded at the infection site by HAase, HA-based nanoparticles allow enhanced and targeted antibacterial delivery. Herein, we present a comprehensive and up-to-date review that highlights various techniques of preparation of HA-based nanoparticles that have been reported in the literature. Furthermore, we also discuss and critically analyze numerous types of HA-based nanoparticles that have been employed in antibacterial delivery to date. This article offers a critical overview of the potential of HA-based nanoparticles to overcome the challenges of conventional antibiotics in the treatment of bacterial infections. Moreover, this review identifies further avenues of research for developing multifunctional and biomimetic HA-based nanoparticles for the treatment, prevention, and/or detection of pathogenic bacteria. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Self-Treatment of Chronic Low Back Pain Based on a Rapid and Objective Sacroiliac Asymmetry Test: A Pilot Study.

BACKGROUND: Low back pain (LBP) is common, costly, and disabling. This study assesses a novel and simple LBP evaluation method and its merit in guiding the direction of a self-treatment exercise. METHODS: Randomized open-label intention is used to treat the study. Consecutive patients with LBP ≥ three months and pain ≥ 5/10 were evaluated in a Vancouver clinic with the sacroiliac forward flexion test (SIFFT) by comparing the height of posterior superior iliac spines using a level. Those with asymmetry ≥ 5 mm were offered participation. The assistant, who generated and encrypted the randomization, assigned participants: group 1 learned a two-minute, SIFFT-derived, sacroiliac-leveling exercise (SIFFT-E) as needed for LBP relief; group 2 used a pelvic stabilization belt as needed to prevent LBP, and group 3 continued the usual care. After one month, all participants used SIFFT-E and belt as needed for one month. The identifier number of this article in Clinicaltrials.gov is #NCT03888235. The trial is closed. Our primary outcome measure was the Oswestry disability index (ODI) (decrease) from baseline to one and two months. We also followed SIFFT improvement (decrease). FINDINGS: Of 72 LBP patients, 62 (86%) had ≥ 5 mm asymmetry. From zero to one month, the 21 (one dropout) SIFFT-E participants outperformed the 20 usual care participants for ODI improvement (12.5 ± 14.8 vs. -3.4 ± 14.9 points; mean difference 15.9 [CI 6.7-25.0]; P = 0.002 with number needed to treat (NNT) of 3.0 for ODI improvement ≥ 11). Belt use results were intermediate. At two months, after all the 62 participants used the exercise and belt as needed, combined ODI improvements were clinically significant (12.0 ± 18.4 points), and SIFFT asymmetry was reduced by 8.6 ± 8.6 mm. Five (8%) exercise and 12 (19%) belt wearers experienced mild side effects. INTERPRETATION: Sacroiliac asymmetry appears to be frequent. SIFFT may be clinically useful as an evaluation tool for prescribing a simple self-directed corrective exercise as seen by clinically significant improvements in function and asymmetry.

Plug-and-play aqueous electrochemical atom transfer radical polymerization.

A simplified 'plug-and-play' approach to aqueous electrochemical atom transfer radical polymerization (eATRP) has been developed. Well-controlled polymerization of PEGA480 (Dm = 1.17-1.31) is reported under potentiostatic (3-electrodes, undivided cell) and galvanostatic (2-electrodes, 6-steps) conditions.

Assessment of COVID-19 Treatment containing both Hydroxychloroquine and Azithromycin: A natural clinical trial.

The goal of this study was to assess the clinical effectiveness and safety profile of the COVID-19 treatment protocol (containing both hydroxychloroquine (HCQ) and azithromycin) in an Iraqi specialised hospital. METHODS: This prospective study used a pre- and post-intervention design without a comparison group. The intervention was routine Ministry of Health (MOH) approved the management of COVID-19 for all patients. The study was conducted in a public healthcare setting in Baghdad, Iraq from March 1st to May 25, 2020. The study outcome measures included the changes in clinical and biochemical parameters during the hospitalisation period. Paired t-test and Chi-square test were used to compare the measures of vital signs, lab tests and symptoms before and after treatment. RESULTS: The study included 161 patients who were admitted with positive RT-PCR and clinical symptoms of COVID-19. In terms of severity, 53 (32.9%) patients had amild condition, 47 (29.2%) had moderate condition, 35 (21.7%) had severe condition and 26 (16.1%) had critical condition. Most patients (84.5%) recovered and were discharged without symptoms after testing negative with RT-PCR, while 11 (6.8%) patients died during the study period. The signs and symptoms of COVID-19 were reduced significantly in response to a therapy regimen containing HCQ and azithromycin. The most common reported side effects were stomach pain, hypoglycemia, dizziness, itching, skin rash, QT prolongation, arrhythmia, and conjunctivitis. CONCLUSIONS: This natural trial showed that the COVID-19 regimen containing both HCQ and azithromycin can be helpful to promote the recovery of most patients and reduced their signs and symptoms significantly. It also shows some manageable side effects mostly those related to heart rhythm. In the absence of FDA-approved medications to treat COVID-19, the repurposing of HCQ and azithromycin to control the disease signs and symptoms can be useful.