An optimized ionizable cationic lipid for brain tumor-targeted siRNA delivery and glioblastoma immunotherapy

Biomaterials, Год журнала: 2022, Номер 287, С. 121645 - 121645

Опубликована: Июнь 22, 2022

Язык: Английский

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Lipid-based nanoparticles to address the limitations of GBM therapy by overcoming the blood-brain barrier, targeting glioblastoma stem cells, and counteracting the immunosuppressive tumor microenvironment

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 171, С. 116113 - 116113

Опубликована: Янв. 5, 2024

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, characterized by high heterogeneity, strong invasiveness, poor prognosis, and a low survival rate. A broad range of nanoparticles have been recently developed as drug delivery systems for GBM therapy owing to their inherent size effect ability cross blood-brain barrier (BBB). Lipid-based (LBNPs), such liposomes, solid lipid NPs (SLNs), nano-structured carriers (NLCs), emerged promising system treatment because unique size, surface modification possibilities, proven bio-safety. In this review, main challenges current clinical strategies on how novel LBNPs overcome them were explored. The application progress LBNP-based in chemotherapy, immunotherapy, gene recent years systematically reviewed, prospect was discussed.

Язык: Английский

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Advances in peptide-based drug delivery systems

Heliyon, Год журнала: 2024, Номер 10(4), С. e26009 - e26009

Опубликована: Фев. 1, 2024

Drug-delivery systems (DDSs) are designed to deliver drugs their specific targets minimize toxic effects and improve susceptibility clearance during targeted transport. Peptides have high affinity, low immunogenicity, simple amino acid composition, adjustable molecular size; therefore, most peptides can be coupled via linkers form peptide-drug conjugates (PDCs) act as active pro-drugs. PDCs widely thought promising DDSs, given ability drug bio-compatibility physiological stability. Peptide-based DDSs often used therapeutic substances such anti-cancer nucleic acid-based drugs, which not only slow the degradation rate of in vivo but also ensure concentration at site prolong half-life vivo.This article provides an profile advancements future development functional peptide-based delivery both domestically internationally recent years, expectation achieving incorporating taking full advantage synergistic effects.

Язык: Английский

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Lipidic and Inorganic Nanoparticles for Targeted Glioblastoma Multiforme Therapy: Advances and Strategies

Micro, Год журнала: 2025, Номер 5(1), С. 2 - 2

Опубликована: Янв. 3, 2025

Due to their biocompatibility, nontoxicity, and surface conjugation properties, nanomaterials are effective nanocarriers capable of encapsulating chemotherapeutic drugs facilitating targeted delivery across the blood–brain barrier (BBB). Although research on nanoparticles for brain cancer treatment is still in its early stages, these systems hold great potential revolutionize drug delivery. Glioblastoma multiforme (GBM) one most common lethal tumors, heterogeneous aggressive nature complicates current treatments, which primarily rely surgery. One significant obstacles poor penetration BBB. Moreover, GBM often referred as a “cold” tumor, characterized by an immunosuppressive tumor microenvironment (TME) minimal immune cell infiltration, limits effectiveness immunotherapies. Therefore, developing novel, more treatments critical improving survival rate patients. Current strategies enhancing outcomes focus controlled, agents cells BBB using nanoparticles. These therapies must be designed engage specialized transport systems, allowing efficient penetration, improved therapeutic efficacy, reduced systemic toxicity degradation. Lipid inorganic can enhance while minimizing side effects. formulations may include epitopes—small antigen fragments that bind directly free antibodies, B receptors, or T receptors—that interact with enable crossing, thereby boosting efficacy. Lipid-based (LNPs), such liposomes, niosomes, solid lipid (SLNs), nanostructured carriers (NLCs), among promising due unique including size, modification capabilities, proven biosafety. Additionally, gold nanoparticles, mesoporous silica, superparamagnetic iron oxide dendrimers offer alternatives. Inorganic (INPs) easily engineered, surfaces modified various elements biological ligands delivery, biocompatibility. Strategies engineering functionalization have been employed ensure biocompatibility reduce cytotoxicity, making safer clinical applications. The use INPs has shown promise efficacy traditional like chemotherapy, radiotherapy, gene therapy, well advancing newer strategies, immunotherapy, photothermal photodynamic therapies, magnetic hyperthermia. This article reviews latest treating GBM, focusing active passive targeting approaches.

Язык: Английский

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Antimicrobial and Cell-Penetrating Peptides: Understanding Penetration for the Design of Novel Conjugate Antibiotics

Antibiotics, Год журнала: 2022, Номер 11(11), С. 1636 - 1636

Опубликована: Ноя. 16, 2022

Antimicrobial peptides (AMPs) are short oligopeptides that can penetrate the bacterial inner and outer membranes. Together with cell-penetrating (CPPs), they called membrane active peptides; which translocate across biological Over last fifty years, attempts have been made to understand molecular features drive interactions of membranes peptides. This review examines a these exploit for translocation, as well physicochemical characteristics important translocation. Moreover, it presents examples how used in recent years create conjugates consisting peptide, “vector”, attached either current or novel antibiotic, “cargo” “payload”. In addition, discusses what properties may contribute an ideal peptide vector able deliver cargoes rising issue antimicrobial resistance demands new strategies be employed combat this global public health threat.

Язык: Английский

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Structure-aware machine learning strategies for antimicrobial peptide discovery

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Май 25, 2024

Machine learning models are revolutionizing our approaches to discovering and designing bioactive peptides. These often need protein structure awareness, as they heavily rely on sequential data. The excel at identifying sequences of a particular biological nature or activity, but frequently fail comprehend their intricate mechanism(s) action. To solve two problems once, we studied the mechanisms action structural landscape antimicrobial peptides (i) membrane-disrupting peptides, (ii) membrane-penetrating (iii) protein-binding By analyzing critical features such dipeptides physicochemical descriptors, developed with high accuracy (86-88%) in predicting these categories. However, initial (1.0 2.0) exhibited bias towards α-helical coiled structures, influencing predictions. address this bias, implemented subset selection data reduction strategies. former gave three structure-specific for likely fold into α-helices (models 1.1 2.1), coils (1.3 2.3), mixed structures (1.4 2.4). latter depleted over-represented leading structure-agnostic predictors 1.5 2.5. Additionally, research highlights sensitivity important different classes across models.

Язык: Английский

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Computational Insights into Membrane Disruption by Cell-Penetrating Peptides

Journal of Chemical Information and Modeling, Год журнала: 2025, Номер unknown

Опубликована: Янв. 17, 2025

Cell-penetrating peptides (CPPs) can translocate into cells without inducing cytotoxicity. The internalization process implies several steps at different time scales ranging from microseconds to minutes. We combine adaptive Steered Molecular Dynamics (aSMD) with conventional (cMD) observe nonequilibrium and equilibrium states study the early mechanisms of peptide–bilayer interaction leading CPPs internalization. define three membrane compositions representing bilayer sections, neutral lipids (i.e., upper leaflet), cholesterol hydrophobic core), neutral/negatively charged lower leaflet) energy barriers disruption Arg9, MAP, TP2, cationic, amphiphilic, CPPs, respectively. Cholesterol negatively increase energetic for crossing. TP2 interacts by insertion, while Arg9 disrupts forming transient or stable pores. MAP has shown both behaviors. Collectively, these findings underscore significance innovative computational approaches in studying membrane-disruptive and, more specifically, harnessing their potential cell penetration.

Язык: Английский

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Peptide Shuttles for Blood–Brain Barrier Drug Delivery

Pharmaceutics, Год журнала: 2022, Номер 14(9), С. 1874 - 1874

Опубликована: Сен. 5, 2022

The blood-brain barrier (BBB) limits the delivery of therapeutics to brain but also represents main gate for nutrient entrance. Targeting natural transport mechanisms BBB offers an attractive route drug delivery. Peptide shuttles are able use these increase compounds that cannot cross unaided. As peptides a group biomolecules with unique physicochemical and structural properties, field peptide has substantially evolved in last few years. In this review, we analyze classifications BBB-peptide leading sources used discover them.

Язык: Английский

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Polyamidoamine Dendrimers: Brain-Targeted Drug Delivery Systems in Glioma Therapy

Polymers, Год журнала: 2024, Номер 16(14), С. 2022 - 2022

Опубликована: Июль 15, 2024

Glioma is the most common primary intracranial tumor, which formed by malignant transformation of glial cells in brain and spinal cord. It has characteristics high incidence, recurrence rate, mortality low cure rate. The treatments for glioma include surgical removal, chemotherapy radiotherapy. Due to obstruction biological barrier tissue, it difficult achieve desired therapeutic effects. To address limitations imposed brain’s natural barriers enhance treatment efficacy, researchers have effectively used brain-targeted drug delivery systems (DDSs) therapy. Polyamidoamine (PAMAM) dendrimers, as branched macromolecular architectures, represent promising candidates studies This review focuses on PAMAM-based DDSs glioma, highlighting their physicochemical characteristics, structural properties well an overview toxicity safety profiles.

Язык: Английский

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Molecular Dynamics Simulations of Drug-Conjugated Cell-Penetrating Peptides

Pharmaceuticals, Год журнала: 2023, Номер 16(9), С. 1251 - 1251

Опубликована: Сен. 5, 2023

Cell-penetrating peptides (CPPs) are small capable of translocating through biological membranes carrying various attached cargo into cells and even the nucleus. They may also participate in transcellular transport. Our silico study intends to model several their conjugates. We have selected three CPPs with a linear backbone, including penetratin, naturally occurring oligopeptide; two its modified sequence analogues (6,14-Phe-penetratin dodeca-penetratin); natural cyclic backbone: Kalata B1, Sunflower trypsin inhibitor 1 (SFT1), Momordica cochinchinensis II (MCoTI-II). built conjugates small-molecule drug compounds doxorubicin, zidovudine, rasagiline for each peptide. Molecular dynamics (MD) simulations were carried out explicit membrane models. The analysis trajectories showed that interaction penetratin led spectacular rearrangements secondary structure peptide, while remained unchanged due high conformational stability. Membrane-peptide membrane-conjugate interactions been identified compared. Taking account well-known examples from literature, our demonstrated utility computational methods CPP complexes, they contribute better understanding mechanism penetration, which could serve as basis delivering conjugated molecules intracellular targets.

Язык: Английский

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