Red Blood Cell Membrane-Camouflaged Tedizolid Phosphate-Loaded PLGA Nanoparticles for Bacterial-Infection Therapy

Abstract

Multiple drug resistance (MDR) in bacterial infections is developed with the abuse of antibiotics, posing a severe threat to global health. Tedizolid phosphate (TR-701) is an efficient prodrug of tedizolid (TR-700) against gram-positive bacteria, including methicillin-sensitive staphylococcus aureus (MSSA) and methicillin-resistant staphylococcus aureus (MRSA). Herein, a novel drug delivery system: Red blood cell membrane (RBCM) coated TR-701-loaded polylactic acid-glycolic acid copolymer (PLGA) nanoparticles (RBCM-PLGA-TR-701NPs, RPTR-701Ns) was proposed. The RPTR-701Ns possessed a double-layer core-shell structure with 192.50 ± 5.85 nm in size, an average encapsulation efficiency of 36.63% and a 48 h-sustained release in vitro. Superior bio-compatibility was confirmed with red blood cells (RBCs) and HEK 293 cells. Due to the RBCM coating, RPTR-701Ns on one hand significantly reduced phagocytosis by RAW 264.7 cells as compared to PTR-701Ns, showing an immune escape effect. On the other hand, RPTR-701Ns had an advanced exotoxins neutralization ability, which helped reduce the damage of MRSA exotoxins to RBCs by 17.13%. Furthermore, excellent in vivo bacteria elimination and promoted wound healing were observed of RPTR-701Ns with a MRSA-infected mice model without causing toxicity. In summary, the novel delivery system provides a synergistic antibacterial treatment of both sustained release and bacterial toxins absorption, facilitating the incorporation of TR-701 into modern nanotechnology.

Nanotechnology-Based Diagnostic and Therapeutic Strategies for Neuroblastoma

“…In addition to traditional therapeutic approaches, novel approaches focusing on the suppression of NB cell growth and malignant phenotype based on programmed cell death are ongoing directions in nanomedicine, such as ferroptosis induction ( Zafar et al, 2021 ). Furthermore, some researchers achieved drug loading and transport by effectively utilizing the physiological conditions of the organism itself as biocompatible carriers for the purpose of certain tumor treatment, such as red blood cells (RBCs) ( Li et al, 2021b ; Wu et al, 2021 ). Most of the previous studies on the application of nanomaterials in NB diagnostics and therapeutics are mainly conducted through cellular and animal experiments, and more efforts are required to accomplish the clinical translation of these scientific findings.…”

Red Blood Cell Membrane-Camouflaged PLGA Nanoparticles Loaded With Basic Fibroblast Growth Factor for Attenuating Sepsis-Induced Cardiac Injury

“…In addition, therapeutic functions of PLGA microspheres in the delivery of a controlled-release matrix of bFGF and regeneration of the sciatic nerve have been confirmed ( Si et al, 2017 ). Recently, novel strategies have been developed for longer circulation and less immune recognition of nanoparticles; they include modification with polyethylene glycol (PEG), cell-penetrating peptides, and cell-derived membranes of macrophages, dendritic cells, stems cells, and red blood cells (RBCs) ( Shreffler et al, 2019 ; Wu et al, 2021 ). Particularly, cell membranes of RBCs have been of much focus due to the excellent biocompatibility, accessibility, and long half-life of RBCs, which are the most abundant cells in the blood ( Gao et al, 2017 ).…”

Engineered Exosomes-Based Photothermal Therapy with MRI/CT Imaging Guidance Enhances Anticancer Efficacy through Deep Tumor Nucleus Penetration

“…Nanoparticles (NPs)-based diagnosis and treatment platforms have presented good therapeutic efficiency in cancer. Many artificial NPs have been constructed for cancer diagnosis and therapy [ 1 , 2 , 3 ]. However, developing a promising theranostic platform still faces great challenges.…”