Purpose: Receptor-mediated transcytosis (RMT) is a more specific, highly efficient, and reliable approach to crossing the blood-brain-barrier (BBB) and releasing the therapeutic cargos into the brain parenchyma.
Methods: Here, we introduced and characterized a human/mouse-specific novel leptin-derived peptide using , and experiments.
Results: Based on the bioinformatics analysis and molecular dynamics (MD) simulation, a 14 amino acid peptide sequence (LDP 14) was introduced and its interaction with leptin-receptor (ObR) was analyzed in comparison with an well known leptin-derived peptide, Lep 30.
Background: Breast cancer is a multifaceted disease characterized by genetic and epigenetic changes that lead to uncontrolled cell growth and metastasis. Early detection and treatment are crucial for managing diseases.
Objectives: The objective of this study is to investigate the potential of chimeric peptides for drug delivery and to identify biomarkers associated with breast cancer.
Ovarian cancer (OC) incidence and mortality rates continue to escalate globally. Early detection of OC is challenging due to extensive metastases and the ambiguity of biomarkers in advanced High-Grade Primary Tumors (HGPTs). In the present study, we conducted an in-depth in silico analysis in OC cell lines using the Gene Expression Omnibus (GEO) microarray dataset with 53 HGPT and 10 normal samples.
View Article and Find Full Text PDFSalinomycin is a polyether compound that exhibits strong anticancer activity and is known as the cancer stem cell inhibitor that reached clinical testing. The rapid elimination of nanoparticles from the bloodstream by the mononuclear phagocyte system (MPS), the liver, and the spleen, accompanied by protein corona (PC) formation, restricts in vivo delivery of nanoparticles in the tumor microenvironment (TME). The DNA aptamer (TA1) that successfully targets the overexpressed CD44 antigen on the surface of breast cancer cells suffers strongly from PC formation in vivo.
View Article and Find Full Text PDFBlood-brain barrier with strictly controlled activity participates in a coordinated transfer of bioactive molecules from the blood to the brain. Among different delivery approaches, gene delivery is touted as a promising strategy for the treatment of several nervous system disorders. The transfer of exogenous genetic elements is limited by the paucity of suitable carriers.
View Article and Find Full Text PDFRecent advances in extracellular vesicle (EVs) detection and isolation methods have led to the development of novel therapeutic modalities. Among different types of EVs, exosomes (Exos) can transfer different signaling biomolecules and exhibit several superior features compared to whole-cell-based therapies. Therapeutic factors are normally loaded into the Exo lumen or attached to their surface for improving the on-target delivery rate and regenerative outcomes.
View Article and Find Full Text PDFFingolimod (Fin), an FDA-approved drug, is used to control relapsing-remitting multiple sclerosis (MS). This therapeutic agent faces crucial drawbacks like poor bioavailability rate, risk of cardiotoxicity, potent immunosuppressive effects, and high cost. Here, we aimed to assess the therapeutic efficacy of nano-formulated Fin in a mouse model of experimental autoimmune encephalomyelitis (EAE).
View Article and Find Full Text PDFAt the moment, anaplastic changes within the brain are challenging due to the complexity of neural tissue, leading to the inefficiency of therapeutic protocols. The existence of a cellular interface, namely the blood-brain barrier (BBB), restricts the entry of several macromolecules and therapeutic agents into the brain. To date, several nano-based platforms have been used in laboratory settings and in vivo conditions to overcome the barrier properties of BBB.
View Article and Find Full Text PDFAs a common belief, most viruses can egress from the host cells as single particles and transmit to uninfected cells. Emerging data have revealed en bloc viral transmission as lipid bilayer-cloaked particles via extracellular vesicles especially exosomes (Exo). The supporting membrane can be originated from multivesicular bodies during intra-luminal vesicle formation and autophagic response.
View Article and Find Full Text PDFHere, we investigated the photothermal effect of gold nanorods (GNRs) on human neuroblastoma CD133 cancer stem cells (CSCs) via autophagic cell death. GNRs were synthesized using Cetyltrimethylammonium bromide (CTAB), covered with bovine serum albumin (BSA). CD133 CSCs were enriched from human neuroblastoma using the magnetic-activated cell sorting (MACS) technique.
View Article and Find Full Text PDFThe key issue in the treatment of solid tumors is the lack of efficient strategies for the targeted delivery and accumulation of therapeutic cargoes in the tumor microenvironment (TME). Targeting approaches are designed for more efficient delivery of therapeutic agents to cancer cells while minimizing drug toxicity to normal cells and off-targeting effects, while maximizing the eradication of cancer cells. The highly complicated interrelationship between the physicochemical properties of nanoparticles, and the physiological and pathological barriers that are required to cross, dictates the need for the success of targeting strategies.
View Article and Find Full Text PDFFor successful translation of targeting nanomedicines from bench to bedside, it is vital to address their most common drawbacks namely rapid clearance and off-target accumulation. These complications evidently originate from a phenomenon called "protein corona (PC) formation" around the surface of targeting nanoparticles (NPs) which happens once they encounter the bloodstream and interact with plasma proteins with high collision frequency. This phenomenon endows the targeting nanomedicines with a different biological behavior followed by an unexpected fate, which is usually very different from what we commonly observe in vitro.
View Article and Find Full Text PDFUnraveling unwanted side effects of nanotechnology-based therapies like photothermal therapy (PTT) is vital in translational nanomedicine. Herein, we monitored the relationship between autophagic response at the transcriptional level by using a PCR array and tumor formation ability by colony formation assay in the human neuroblastoma cell line, SH-SY5Y, 48 h after being exposed to two different mild hyperthermia (43 and 48 °C) induced by PTT. In this regard, the promotion of apoptosis and autophagy were evaluated using immunofluorescence imaging and flow cytometry analyses.
View Article and Find Full Text PDFThis study aimed to design gentamicin-conjugated poly (amidoamine) (PAMAM) dendrimers to increase the therapeutic efficiency of gentamicin against . Gentamicin-presenting dendrimers were synthesized using MAL-PEG-NHS as a redox-sensitive linker to attach gentamicin to the surface of G4 PAMAM dendrimers. The gentamicin molecules were thiolated by using Traut reagent.
View Article and Find Full Text PDFIn recent years, smart/stimuli-responsive hydrogels have drawn tremendous attention for their varied applications, mainly in the biomedical field. These hydrogels are derived from different natural and synthetic polymers but are also composite with various organic and nano-organic fillers. The basic functions of smart hydrogels rely on their ability to change behavior; functions include mechanical, swelling, shaping, hydrophilicity, and bioactivity in response to external stimuli such as temperature, pH, magnetic field, electromagnetic radiation, and biological molecules.
View Article and Find Full Text PDFThe formation of protein corona (PC) around nanoparticles (NPs) has been reported inside biological conditions. This effect can alter delivery capacity toward the targeted tissues. Here, we synthesized folic acid-modified chitosan NPs (FA-CS NPs) using different concentrations of folic acid (5, 10, and 20%).
View Article and Find Full Text PDFAdjuvant-aided combination chemotherapy is one of the most effective ways of cancer treatment by overcoming the multidrug resistance (MDR) and reducing the side-effects of anticancer drugs. In this study, Conferone (Conf) was used as an adjuvant in combination with Doxorubicin (Dox) for inducing apoptosis to MDA-MB-231 cells. Herein, the novel biodegradable amphiphilic β-cyclodextrin grafted poly maleate-co-PLGA was synthesized by thiol-ene addition and ring-opening process.
View Article and Find Full Text PDFHydrophilic drugs are extensively applied in clinical applications. Inadequate dermal penetration of these drugs is a great challenge. Incorporation of drugs into nano-carrier systems overcomes lower penetration drawbacks.
View Article and Find Full Text PDFThe transcription factor high mobility group protein A2 (HMGA2) plays an important role in the pathogenesis of some cancers including breast cancer. Polyamidoamine dendrimer generation 4 is a kind of highly branched polymeric nanoparticle with surface charge and highest density peripheral groups that allow ligands or therapeutic agents to attach it, thereby facilitating target delivery. Here, methotrexate (MTX)- modified polyamidoamine dendrimer generation 4 (G4) (G4/MTX) was generated to deliver specific small interface RNA (siRNA) for suppressing HMGA2 expression and the consequent effects on folate receptor (FR) expressing human breast cancer cell lines (MCF-7, MDA-MB-231).
View Article and Find Full Text PDFNowadays, a large population around the world, especially the elderly, suffers from neurological inflammatory and degenerative disorders/diseases. Current drug delivery strategies are facing different challenges because of the presence of the BBB, which limits the transport of various substances and cells to brain parenchyma. Additionally, the low rate of successful cell transplantation to the brain injury sites leads to efforts to find alternative therapies.
View Article and Find Full Text PDFAutoimmune diseases (AD), which are classified as chronic injuries, are caused by a specific auto-reactive reaction. The etiology of most ADs is not well understood. Meanwhile, Autophagy is a protective response defining as a catabolic method by lysosomes tending to maintain homeostasis acts by recycling and discrediting cell compartments.
View Article and Find Full Text PDFMost commonly recognized as a catabolic pathway, autophagy is a perplexing mechanism through which a living cell can free itself of excess cytoplasmic components, i.e., organelles, by means of certain membranous vesicles or lysosomes filled with degrading enzymes.
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