The greatest obstacle to clinical application of cancer gene therapy is lack of effective delivery tools. Gene delivery vehicles must protect against degradation, avoid immunogenic effects and prevent off target delivery which can cause harmful side effects. PEGylated liposomes have greatly improved tumor localization of small molecule drugs and are a promising tool for nucleic acid delivery as the polyethylene glycol (PEG) coating protects against immune recognition and blood clearance. In this study, small interfering RNA (siRNA) was fully encapsulated within PEGylated liposomes by complexing the siRNA with a cationic polymer, polyethyleneimine (PEI), before encapsulation. Formation methods and material compositions were then investigated for their effects on encapsulation. This technology was translated for protective delivery of siRNA designed for human papillomavirus (HPV) viral gene silencing and cervical cancer treatment. PEGylated liposomes encapsulating siRNA were functionalized with the AG86 targeting peptide-amphiphile which binds to the αβ integrin, a cervical cancer biomarker. It was found that both targeting and polymer complexation before encapsulation were critical components to effective transfection.
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http://dx.doi.org/10.1002/btm2.10022 | DOI Listing |
Leuk Lymphoma
January 2025
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
This retrospective study aimed to evaluate the efficacy and safety of PBVD (pegylated liposomal doxorubicin [PLD], bleomycin, vinblastine, and dacarbazine) in the first-line treatment of classical Hodgkin lymphoma (cHL) patients with cardiovascular risk factors. Overall, 84 patients (53 had stage I-II and 31 had stage III-IV disease) received PBVD. The median PLD treatment duration was 16 weeks (interquartile range [IQR]: 8-24) for stage I-II and 24 weeks (IQR: 12-24) for stage III-IV.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most prevalent form of late-life dementia. The ε2 allele of the APOE gene encoding apolipoprotein E (APOE2) is associated with lower susceptibility to AD among the three genotypes (ε2, ε3, ε4), while APOE4 is the strongest genetic risk factor for late-onset AD. APOE plays a critical role in maintaining synaptic plasticity and neuronal function by controlling lipid homeostasis, with APOE2 having a superior function.
View Article and Find Full Text PDFACS Nano
January 2025
Department of Biological Science and Technology, Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan.
The blood-brain barrier (BBB) remains a major obstacle for effective delivery of therapeutics to treat central nervous system (CNS) disorders. Although transferrin receptor (TfR)-mediated transcytosis is widely employed for brain drug delivery, the inefficient release of therapeutic payload hinders their efficacy from crossing the BBB. Here, we developed a pH-responsive anti-polyethylene glycol (PEG) × anti-TfR bispecific antibody (pH-PEG engager) that can complex with PEGylated nanomedicine at physiological pH to trigger TfR-mediated transcytosis in the brain microvascular endothelial cells, while rapidly dissociating from PEGylated nanomedicine at acidic endosomes for efficient release of PEGylated nanomedicine to cross the BBB.
View Article and Find Full Text PDFJ Biosci Bioeng
December 2024
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Extracorporeal blood purification techniques using magnetic beads, which physically remove bacteria, fungi, viruses, and cytokines (disease agents) from the blood causing sepsis, have been studied. However, magnetic bead influx, which causes hemolysis and cytotoxicity, is an important issue. This study proposed a novel method for removing Escherichia coli from the blood using liposomes with high biocompatibility.
View Article and Find Full Text PDFBioorg Chem
December 2024
Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia.
Red grapes contain resveratrol (Resv), a polyphenol with anti-inflammatory, anti-diabetic, and anticancer properties. In this study, in silico molecular docking was used to assess the binding affinity of Resv to target proteins. Resv was encapsulated in PEGylated liposomes (LNPs) using Phospholipon 90G, cholesterol, and DSPE-mPEG.
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