M1 macrophage-membrane-cloaked paclitaxel/ß-elemene nanoparticles targeting cervical cancer for enhanced therapy.

Cervical cancer is a leading cause of cancer-related mortality in females worldwide, necessitating urgent solutions for effective treatment. Paclitaxel (PTX), a natural diterpene alkaloid compound, has the ability to inhibit mitosis and induce programmed apoptosis in tumor cells. However, its toxicity and drug resistance limit its efficacy in certain cervical cancer patients. ß-elemene (ß-ELE) can reverse multidrug resistance by inhibiting ATP-binding cassette transporters, thereby enhancing chemotherapy drug retention. Therefore, we propose a combination therapy using PTX/ß-ELE to improve chemotherapy sensitivity. To enhance targeted drug delivery, we developed M1-macrophage-membrane-coated nanoparticles (M1@PLGA/PTX/ß-ELE) for co-delivery of PTX&ß-ELE. Through both in vitro and in vivo cervical cancer models, we demonstrated that M1@PLGA/PTX/ß-ELE effectively suppressed tumor progression and polarization of tumor-associated macrophages. Furthermore, H&E staining confirmed the high therapeutic biosafety of M1@PLGA/PTX/ß-ELE as there was no significant damage observed in major organs throughout the entire therapeutic process. Overall, this study presents a targeted biomimetic nanoplatform and combinatorial strategy that synergistically enhances chemosensitivity in malignant tumors.

Using the synthesized peptide HAYED (5) to protect the brain against iron catalyzed radical attack in a naturally senescence Kunming mouse model.

Alzheimer's disease (AD) is a progressive neurodegenerative disease of the brain. It cannot be cured currently, and those suffering from AD place a great burden on their caregivers and society. AD is characterized by high levels of iron ions in the brain, which catalyze radicals that damage the neurons. Knowing that the Aß42 peptide precipitates iron by binding iron ions at amino acid residues D1, E3, H11, H13, and H14, we synthesized a 5-repeat (HAYED) sequence peptide. By treating iron-stressed SH-SY5Y cells with it and injecting it into the cerebrospinal fluid (CSF) of naturally senescence Kunming mouse, which displaying AD-similar symptoms such as learning and memory dysfunction, neuron degeneration and high level of iron in brain, we found that HAYED (5) decreased the iron and radical levels in the cell culture medium and in the CSF. Specially, the synthesized peptide prevented cell and brain damage. Furthermore, functional magnetic resonance imaging (fMRI), Morris water maze and passive avoidance tests demonstrated that the peptide ameliorated brain blood-oxygen metabolism and slowed cognitive loss in the experimental senescence mice, and clinical and blood tests showed that HAYED (5) was innoxious to the kidney, the liver and blood and offset the AD-associated inflammation and anemia.