Nanomedicine: Nanotechnology, Biology and Medicine最新文献

Universal influenza vaccines are urgently needed to prevent recurrent influenza epidemics and inevitable pandemics. We generated double-layered protein nanoparticles incorporating two conserved influenza antigens—nucleoprotein and neuraminidase—through a two-step desolvation-crosslinking method. These protein nanoparticles displayed immunostimulatory properties to antigen-presenting cells by promoting inflammatory cytokine (IL-6 and TNF-α) secretion from JAWS II dendric cells. The nanoparticle immunization induced significant antigen-specific humoral and cellular responses, including antigen-binding and neutralizing antibodies, antibody- and cytokine (IFN-γ and IL-4)-secreting cells, and NP_147–155 tetramer-specific cytotoxic T lymphocyte (CTL) responses. Co-administration of monophosphoryl lipid A (MPLA, a toll-like receptor 4 agonist) with the protein nanoparticles further improved immune responses and conferred heterologous and heterosubtypic influenza protection. The MPLA-adjuvanted nanoparticles reduced lung inflammation post-infection. The results demonstrated that the combination of MPLA and conserved protein nanoparticles could be developed into an improved universal influenza vaccine strategy.

Benefit for clinical melanoma treatments, the transdermal neoadjuvant therapy could reduce surgery region and increase immunotherapy efficacy. Using lipoplex (Lipo-PEG-PEI-complex, LPPC) encapsulated doxorubicin (DOX) and carrying CpG oligodeoxynucleotide; the transdermally administered nano-liposomal drug complex (LPPC-DOX-CpG) would have high cytotoxicity and immunostimulatory activity to suppress systemic metastasis of melanoma. LPPC-DOX-CpG dramatically suppressed subcutaneous melanoma growth by inducing tumor cell apoptosis and recruiting immune cells into the tumor area. Animal studies further showed that the colonization and growth of spontaneously metastatic melanoma cells in the liver and lung were suppressed by transdermal LPPC-DOX-CpG. Furthermore, NGS analysis revealed IFN-γ and NF-κB pathways were triggered to recruit and activate the antigen-presenting-cells and effecter cells, which could activate the anti-tumor responses as the major mechanism responsible for the therapeutic effect of LPPC-DOX-CpG. Finally, we have successfully proved transdermal LPPC-DOX-CpG as a promising penetrative carrier to activate systemic anti-tumor immunity against subcutaneous and metastatic tumor.

Nanomedicine has revolutionized the available treatment options during the last decade, but poor selectivity of targeted drug delivery and release is still poses a challenge. In this study, doxorubicin (DOX) and magnetite nanoparticles were encapsulated by freezing-induced loading, coated with polymeric shell bearing two bi-layers of polyarginine/dextran sulphate and finally modified with HER2-specific DARPin proteins. We demonstrated that the enhanced cellular uptake of these nanocarriers predominantly occurs by SKOV-3 (HER2+) cells, in comparison to CHO (HER2−) cells, together with the controlled DOX release using low intensity focused ultrasound (LIFU). In addition, a good ability of DARPin+ capsules to accumulate in the tumor and the possibility of combination therapy with LIFU were demonstrated. A relatively high sensitivity of the obtained nanocarriers to LIFU and their preferential interactions with mitochondria in cancer cells make these carriers promising candidates for cancer treatment, including novel approaches to overcome drug resistance.

Rectal cancer is a common cancer, with presently a 5-year survival of 67 %. Treatment is based on tumor stage, but current staging methods, such as magnetic resonance imaging (MRI) or ultrasound, are limited in the ability to correctly stage the disease. Magnetomotive ultrasound is a developing modality that has a potential to improve rectal cancer staging. Magnetic nanoparticles are set in motion by an external magnetic field, and the resulting motion signature is detected by ultrasound. Here, we report on magnetomotive images of magnetic nanoparticles in human tissue, using a prototype system where a rotating permanent magnet provides the varying magnetic field, and an ultrasound transducer array encircling the magnet, detects the induced motion. Prior to surgery, a patient with a low rectal tumor was injected at three sites close to the tumor with magnetic nanoparticles. Postsurgical magnetomotive ultrasound scanning revealed the three injection sites, with no obvious artefactual signals. A phantom study showed detection of nanoparticles beyond 40 mm, where 30 mm is the expected maximum distance to mesorectal lymph nodes.

Magnetomotive ultrasound image of iron oxide nanoparticles in human tissue. Prior to surgery a patient was injected with nanoparticles, and the excised tissue specimen was imaged with a prototype magnetomotive ultrasound system. The three colored areas overlaid on the standard B-mode greyscale image, correspond to the three injection sites.

High-resolution cryogenic transmission electron microscopy (cryo-TEM) evidenced that doxorubicin sulfate crystals in liposomes (prepared by remote loading with ammonium sulfate) form folded, undulating, and fibrous crystals with a diameter of approximately 2.4 nm. An undulating, fibrous crystal considered to be undergrowth, in addition to bundles of fibrous crystals, was also observed in doxorubicin-loaded liposomes. This explains the validity of the formation of doxorubicin sulfate crystals of various shapes, e.g., curved, U-shaped, or circular, in addition to cylinder and/or rod-like crystals reported in the literature. Liposomes that do not contain crystals have inner aqueous phases with high electron density, suggesting that the doxorubicin is remotely loaded and remains as a solute without precipitation.

In recent decades, myocardial regeneration through stem cell transplantation and tissue engineering has been viewed as a promising technique for treating myocardial infarction. As a result, the researcher attempts to see whether co-culturing modified mesenchymal stem cells with Au@Ch-SF macro-hydrogel and H9C2 may help with tissue regeneration and cardiac function recovery. The gold nanoparticles (Au) incorporated into the chitosan-silk fibroin hydrogel (Au@Ch-SF) were validated using spectral and microscopic examinations. The most essential elements of hydrogel groups were investigated in detail, including weight loss, mechanical strength, and drug release rate. Initially, the cardioblast cells (H9C2 cells) was incubated with Au@Ch-SF macro-hydrogel, followed by mesenchymal stem cells (2 × 10⁵) were transplanted into the Au@Ch-SF macro-hydrogel+H9C2 culture at the ratio of 2:1. Further, cardiac phenotype development, cytokines expression and tissue regenerative performance of modified mesenchymal stem cells treatment were studied through various in vitro and in vivo analyses. The Au@Ch-SF macro-hydrogel gelation time was much faster than that of Ch and Ch-SF hydrogels, showing that Ch and SF exhibited greater intermolecular interactions. The obtained Au@Ch-SF macro-hydrogel has no toxicity on mesenchymal stem cells (MS) or cardiac myoblast (H9C2) cells, according to the biocompatibility investigation. MS cells co-cultured with Au@Ch-SF macro-hydrogel and H9C2 cells also stimulated cardiomyocyte fiber restoration, which has been confirmed in myocardial infarction rats using -MHC and Cx43 myocardial indicators. We developed a novel method of co-cultured therapy using MS cells, Au@Ch-SF macro-hydrogel, and H9C2 cells which could promote the regenerative activities in myocardial ischemia cells. These study findings show that co-cultured MS therapy might be effective for the treatment of myocardial injury.

The current challenges in cancer treatment using conventional therapies have made the emergence of nanotechnology with more advancements. The exponential growth of nanoscience has drawn to develop nanomaterials (NMs) with therapeutic activities. NMs have enormous potential in cancer treatment by altering the drug toxicity profile. Nanoparticles (NPs) with enhanced surface characteristics can diffuse more easily inside tumor cells, thus delivering an optimal concentration of drugs at tumor site while reducing the toxicity. Cancer cells can be targeted with greater affinity by utilizing NMs with tumor specific constituents. Furthermore, it bypasses the bottlenecks of indiscriminate biodistribution of the antitumor agent and high administration dosage. Here, we focus on the recent advances on the use of various nanomaterials for cancer treatment, including targeting cancer cell surfaces, tumor microenvironment (TME), organelles, and their mechanism of action. The paradigm shift in cancer management is achieved through the implementation of anticancer drug delivery using nano routes.

Prostate-specific membrane antigen (PSMA) is a prominent biomarker for prostate cancer (PCa) diagnosis. Safe contrast agents able to render the expression and distribution of PSMA would facilitate early accurate screening and prognostic prediction of PCa. However, current Gd-containing nanoparticles are often limited by nonspecific redistribution in mononuclear phagocyte system (MPS) and inadequate perfusion to target sites. Besides, intrinsic defects of magnetic resonance (MR) equipment also hamper their use for precisely depicting PSMA details. Herein, we devised a novel noninvasive MR/CT/NIRF multimodal contrast agent (AGGP) coordinated to a high-affinity PSMA ligand (PSMA1) to specifically detect and quantify PSMA expression in PCa lesions, which exhibited formidable tripe-modal signal augments, preferential PSMA targeting, effective MPS escaping and profitable renal-clearable behavior in living mice. Biocompatibility and histopathological studies substantiated high security of AGGP in vivo, opening the door to future opportunities for improving early-stage PCa detection and clinical implementation of more effective multifunctional nanotherapeutics.

Ferroptosis plays an important role in ischemia-reperfusion (I/R)-induced cardiac injury and there are many defects in current targeted delivery of miRNAs for the treatment of ferroptosis. We herein report a unique hydrogel (Gel) that can be triggered by a near-infrared-II (NIR-II) light with deep tissue penetration and biocompatible maximum permissible exposure (MPE) value for in situ treatment after I/R. The mir-196c-3p mimic (mimics) and photothermal nanoparticles (BTN) were co-encapsulated in an injectable Gel (mimics + Gel/BTN) with NIR-II light-triggered release. Using 1064 nm light irradiation, local microenvironment photothermal-triggered on-demand noninvasive controllable delivery of miRNA was achieved, aiming to inhibit I/R-induced ferroptosis. Consequently, declined ferroptosis in cardiomyocytes and improved cardiac function, survival rate in rats was achieved through the controlled release of Gel/BTN mimics in I/R model to simultaneously inhibit ferroptosis hub genes NOX4, P53, and LOX expression.

Emerging clinically required α-synuclein (α-syn) inhibitor which acts as a neuroprotective nanocomposite drug is in increased demand as a patient-safe central nervous system therapeutic. This inhibitor is intended to chemically engineer graphene quantum dot (GQD) with blue luminescence, and stands to be a potential cure for Parkinson's disease. It has been theorized that α-syn aggregation is a critical step in the development of Parkinson's. Hence narrow the target by α-syn inhibition, through chemically synthesize methyl N-allyl N-benzoylmethioninate (MABM) and functionally engineer the surface of GQD to target the brain delivery on C57BL/6 mice. Spectroscopic and simulation studies confirm defibrillation through the interaction between N-terminal amino acids and MABM-GQD nanoparticles, which makes nontoxic α-syn. Therefore, this drug's ability to cross the blood-brain barrier in vitro functionally prevents neuronal loss in neuroblastoma cells. Thus, in vivo cerebral blood flow analysis using magnetic resonance imaging illustrates, how this nanocomposite can possibly treat Parkinson's.