Construction of homologous cancer cell membrane camouflage in a nano-drug delivery system for the treatment of lymphoma.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) possesses great heterogeneity in cytogenetics, immunophenotype and clinical features, and chemotherapy currently serves as the main treatment modality. Although employing monoclonal antibody targeted drugs has significantly improved its overall efficacy, various patients continue to suffer from drug resistance or recurrence. Chinese medicine has long been used in the treatment of malignant tumors. Therefore, we constructed a low pH value sensitivity drug delivery system based on the cancer cell membrane modified mesoporous silica nanoparticles loaded with traditional Chinese medicine, which can reduce systemic toxicity and improve the therapeutic effect for the targeted drug delivery of tumor cells. RESULTS: Accordingly, this study put forward the construction of a nano-platform based on mesoporous silica nanoparticles (MSNs) loaded with the traditional Chinese medicine isoimperatorin (ISOIM), which was camouflaged by the cancer cell membrane (CCM) called CCM@MSNs-ISOIM. The proposed nano-platform has characteristics of immune escape, anti-phagocytosis, high drug loading rate, low pH value sensitivity, good biocompatibility and active targeting of the tumor site, blocking the lymphoma cell cycle and promoting mitochondrial-mediated apoptosis. CONCLUSIONS: Furthermore, this study provides a theoretical basis in finding novel clinical treatments for lymphoma.

Novel Multifunctional Silver Nanocomposite Serves as a Resistance-Reversal Agent to Synergistically Combat Carbapenem-Resistant Acinetobacter baumannii.

In the face of the abundant production of various types of carbapenemases, the antibacterial efficiency of imipenem, seen as "the last line of defense", is weakening. Following, the incidence of carbapenem-resistant Acinetobacter baumannii (CRAB), which can generate antibiotic-resistant biofilms, is increasing. Based on the superior antimicrobial activity of silver nanoparticles against multifarious bacterial strains compared with common antibiotics, we constructed the IPM@AgNPs-PEG-NOTA nanocomposite (silver nanoparticles were coated with SH-PEG-NOTA as well as loaded by imipenem) whose core was a silver nanoparticle to address the current challenge, and IPM@AgNPs-PEG-NOTA was able to function as a novel smart pH-sensitive nanodrug system. Synergistic bactericidal effects of silver nanoparticles and imipenem as well as drug-resistance reversal via protection of the ß-ring of carbapenem due to AgNPs-PEG-NOTA were observed; thus, this nanocomposite confers multiple advantages for efficient antibacterial activity. Additionally, IPM@AgNPs-PEG-NOTA not only offers immune regulation and accelerates tissue repair to improve therapeutic efficacy in vivo but also can prevent the interaction of pathogens and hosts. Compared with free imipenem or silver nanoparticles, this platform significantly enhanced antibacterial efficiency while increasing reactive oxygen species (ROS) production and membrane damage, as well as affecting cell wall formation and metabolic pathways. According to the results of crystal violet staining, LIVE/DEAD backlight bacterial viability staining, and real-time quantitative polymerase chain reaction (RT-qPCR), this silver nanocomposite downregulated the levels of ompA expression to prevent formation of biofilms. In summary, this research demonstrated that the IPM@AgNPs-PEG-NOTA nanocomposite is a promising antibacterial agent of security, pH sensitivity, and high efficiency in reversing resistance and synergistically combatting carbapenem-resistant A. baumannii. In the future, various embellishments and selected loads for silver nanoparticles will be the focus of research in the domains of medicine and nanotechnology.