Curvature-mediated rapid extravasation and penetration of nanoparticles against interstitial fluid pressure for improved drug delivery

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(22)

Опубликована: Май 20, 2024

Elevated interstitial fluid pressure (IFP) within pathological tissues (e.g., tumors, obstructed kidneys, and cirrhotic livers) creates a significant hindrance to the transport of nanomedicine, ultimately impairing therapeutic efficiency. Among these tissues, solid tumors present most challenging scenario. While several strategies through reducing tumor IFP have been devised enhance nanoparticle delivery, few approaches focus on modulating intrinsic properties nanoparticles effectively counteract during extravasation penetration, which are precisely stages by elevated IFP. Herein, we propose an innovative solution engineering with fusiform shape high curvature, enabling efficient surmounting barriers penetration tissues. Through experimental theoretical analyses, demonstrate that elongated highest mean curvature outperform spherical rod-shaped counterparts against IFP, leading superior intratumoral accumulation antitumor efficacy. Super-resolution microscopy molecular dynamics simulations uncover underlying mechanisms in contributes diminished drag force high-pressure differentials extravasation. Simultaneously, facilitated rotational movement augments hopping frequency penetration. This study addresses limitations posed impediments, uncovers mutual interactions between physical NPs their environment, presents promising avenue for advancing cancer treatment nanomedicine.

Язык: Английский

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Homologous-adhering/targeting cell membrane- and cell-mediated delivery systems: a cancer-catch-cancer strategy in cancer therapy

Regenerative Biomaterials, Год журнала: 2024, Номер 12

Опубликована: Ноя. 20, 2024

Abstract Low tumor enrichment remains a serious and urgent problem for drug delivery in cancer therapy. Accurate targeting of sites is still critical aim Though there have been variety strategies to improve the enrichment, biological barriers cause most delivered guests fail or be excreted before they work. Recently, cell membrane-based systems attracted huge amount attention due their advantages such as easy access, good biocompatibility immune escape, which contribute biomimetic structures specific surface proteins. Furthermore, are referred homologous-targeting function exhibit significantly high adhesion internalization homologous-type cells even though exact mechanism not entirely revealed. Here, we summarize sources characterizations membrane systems, including reconstructed single hybrid nano-/microcarriers, well engineered cells. Additionally, advanced applications these therapy categorized summarized according components membranes. The potential factors related homologous also discussed. By discussing applications, challenges opportunities, expect far-reaching development preclinic clinics.

Язык: Английский

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Versatile Platforms of Microneedle Patches Loaded with Responsive Nanoparticles: Synthesis and Promising Biomedical Applications

Advanced NanoBiomed Research, Год журнала: 2024, Номер 4(4)

Опубликована: Фев. 15, 2024

Microneedle array systems loaded with responsive nanoparticles have received increasing attention due to the advantages of good drug stability, targeting ability, controlled release drugs, high bioavailability, painlessness, and patient compliance. Compared oral delivery, microneedle transdermal delivery eliminates need pass through gastrointestinal tract liver, reducing metabolic consumption drugs by first‐pass effect. While compared intravenous reduces discomfort does not require professional administration. However, there are few review articles on microneedles nanoparticles. Herein, current researches specific such as glucose‐responsive, pH‐responsive, enzyme‐responsive, light‐responsive, magnetic‐responsive, ultrasound‐responsive, multiresponsive, biomedical application these summarized. In addition, challenges prospects strategies briefly discussed, which will facilitate development versatile drug‐delivery strategy.

Язык: Английский

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Nanometerizing Taxifolin Into Selenized Liposomes to Ameliorate Its Hypoglycemic Effect by Optimizing Drug Release and Bioavailability

International Journal of Nanomedicine, Год журнала: 2025, Номер Volume 20, С. 2225 - 2240

Опубликована: Фев. 1, 2025

Diabetes mellitus (DM) remains a significant health challenge, with traditional treatments often failing to provide lasting solutions. Taxifolin (Tax), potential phytomedicine antioxidant and anti-hyperglycemic properties, suffers from low water solubility poor bioavailability, necessitating advanced delivery systems. This study aims nanometerize taxifolin (Tax) into selenized liposomes (Tax-Se@LPs) for enhanced oral hypoglycemic effect. Tax-Se@LPs were fabricated through thin-film hydration/in situ reduction technique. The resulting nanomedicine was characterized in vitro release studies, pharmacokinetic pharmacodynamic evaluations, cellular uptake assays, formulation stability tests. optimized demonstrated an average particle size of 185.3 nm entrapment efficiency 95.25% after optimization. In studies revealed that exhibited slower more sustained profile compared conventional liposomes, favoring gastrointestinal drug absorption. Pharmacokinetic evaluations normal rats indicated achieved relative bioavailability 216.65%, significantly higher than Tax suspensions unmodified liposomes. Furthermore, diabetic GK rats, resulted maximal blood glucose 46.8% therapeutic duration other formulations. Cellular tests manifested selenization altered the internalization mechanisms while preserving their absorption aptness by intestinal epithelial cells. physiological also reinforced selenization. Overall, not only improve but enhance its efficacy. These findings underscore as promising strategy DM management.

Язык: Английский

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Biomimetic gold nano-modulator for deep-tumor NIR-II photothermal immunotherapy via gaseous microenvironment remodeling strategy

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Март 18, 2025

Effective immunotherapeutic treatment of solid tumors has been greatly challenged by the complex hostile tumor immunosuppressive microenvironment (TIME), which typically involves hypoxia and immunosuppression. Herein, a multifunctional biomimetic gold nano-modulator (denoted as GNR-SNO@MMT) was developed to realize efficient second near-infrared (NIR-II) photothermal immunotherapy via targeting deep penetration, vascular normalization immune reprogramming. NIR-II agent nanorods (GNR) were grafted with thermosensitive S-nitrosothiol (SNO) donors camouflaged tumor-penetrating peptide tLyp-1-modified macrophage membrane (MM) yield GNR-SNO@MMT. The engineered coating increased capacity for inflammatory tropism aided GNR-SNO@MMT in ablating together laser irradiation. Moreover, hyperthermia-stimulated nitric oxide (NO) release situ acted gas immunomodulator effectively enhance blood perfusion reprogram TIME multiple functions (e.g., decreasing PD-L1, repolarizing tumor-associated macrophages, revitalizing cytotoxic T cells). Ultimately, inhibition rate against 4T1 mouse mammary model mediated plus 94.7% 2.4-fold CD8+ cells infiltrated into than that untreated counterpart. provides an effective novel photoimmunotherapy candidate deep-sited through reconfiguration NO-involved nanomedicine external assistance.

Язык: Английский

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Direct Cytosolic Delivery of Nanovesicles via Gigahertz Acoustic Streaming

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

The development of advanced intracellular delivery systems is essential for biopharmaceutical progress, particularly in drug systems, genetic engineering, and cellular therapeutics. While nanovesicles show significant therapeutic potential, challenges remain due to cell membrane barriers the limitations endocytosis-mediated pathways. In this study, we introduce an efficient acoustofluidic system that utilizes a gigahertz (GHz)-range bulk acoustic wave (BAW) resonator generate spatiotemporally controlled streaming vortices. This enables rapid (within 10 min) highly direct cytosolic by bypassing conventional endosomal entrapment It effectively delivers both synthetic carriers (doxorubicin-loaded small unilamellar vesicles, Dox-SUVs) biologically active exosomes through GHz-driven hydrodynamic shear forces induce transient permeability while maintaining viability (>91.5% at 300 mW). Key performances demonstrate 86.5% efficiency Dox-SUVs with near-complete nuclear accumulation, exosome-mediated exhibits 2.4-fold accelerated migration 3-fold proliferation enhancement within 24 h. system's capacity modulate fluidic stresses via BAW power tuning (100-500 mW) allows precise control over permeabilization kinetics cargo flux. By overcoming endolysosomal sequestration noninvasive, physics-driven mechanism, approach expands opportunities next-generation therapeutics, including macromolecular biologic delivery, genome editing, intercellular communication.

Язык: Английский

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Tailored “Three-stage booster” nano-extinguisher for synergistic treatment of severe acute pancreatitis by rectifying mitochondrial dysfunction and inhibiting pancreatic autodigestion

Acta Biomaterialia, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

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Colorectal cancer cell exosome and cytoplasmic membrane for homotypic delivery of therapeutic molecules

International Journal of Pharmaceutics, Год журнала: 2023, Номер 646, С. 123456 - 123456

Опубликована: Сен. 29, 2023

Colorectal cancer (CRC) is one of the most common causes death in world. The multi-drug resistance, especially metastatic colorectal cancer, drives development new strategies that secure a positive outcome and reduce undesirable side effects. Nanotechnology has made an impact addressing some pharmacokinetic safety issues related to administration free therapeutic agents. However, demands managing complex biointerfacing require equally methods for introducing stimuli-responsive or targeting elements. In order procure more efficient solution overcoming biological barriers, physiological functions cell plasma exosomal membranes provided source highly functionalized coatings. Biomimetic nanovehicles based on imparted enhanced compatibility, immune escape protection diverse classes molecules. When loaded with load used as coating other nanovehicles, they provide selective uptake. This review presents detailed overview recent application homotypic biomimetic management CRC. We also address current possibilities challenges associated CRC membrane biomimetics.

Язык: Английский

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PAFerroptosis Combined with Metabolic Disturbance of Mito by p52‐ZER6 for Enhanced Cancer Immunotherapy induced by Nano‐Bacilliform‐Enzyme

Advanced Healthcare Materials, Год журнала: 2024, Номер 13(31)

Опубликована: Авг. 22, 2024

Abstract The confused gene expressions and molecular mechanisms for mitochondrial dysfunction of traditional nanoenzymes is a challenge tumor therapy. Herein, nano‐bacilliform‐enzyme obtains the ability to inhibit p52‐ZER6 signal pathway, regulate genes related metabolism, possess GOx/CAT/POD‐like property. NBE acquires catalytic activity from electronic energy transition. tannin as (Mito)‐targeting guide overloads MitoROS, then metabolic disorder lipid peroxidation Mito membrane occurs, thus leading novel death pathway called PAFerroptosis (pyroptosis, apoptosis, Ferroptosis). Simultaneously, in order refrain mitophagy, hydroxychloroquine mixed with form combo strength pyroptosis. As result, NBE/combo improves obviously by activation CD8+T cells inactivation MDSC cells, up‐regulating expression caspase‐3 intercepting DHODH arrive excellent antitumor effect (93%). Therefore, this study establishes rational nanoenzyme without mitophagy effective

Язык: Английский

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Drug delivery systems based on mesoporous silica nanoparticles for the management of hepatic diseases

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 15(2), С. 809 - 833

Опубликована: Дек. 20, 2024

The liver performs multiple life-sustaining functions. Hepatic diseases, including hepatitis, cirrhosis, and hepatoma, pose significant health economic burdens globally. Along with the advances in nanotechnology, mesoporous silica nanoparticles (MSNs) exhibiting diversiform size shape, distinct morphological properties, favorable physico-chemical features have become an ideal choice for drug delivery systems inspire alternative thinking management of hepatic diseases. Initially, we introduce physiological structure highlight its intrinsic cell types correlative Next, detail synthesis methods physicochemical properties MSNs their capacity controlled loading release. Particularly, discuss interactions between respect to passive targeting mechanisms within by adjusting particle size, pore diameter, surface charge, hydrophobicity/hydrophilicity, functionalization. Subsequently, emphasize role regulating pathophysiology, exploring value addressing pathological states, such as tumors inflammation, combined multi-functional designs intelligent modes enhance minimize side effects. Lastly, put forward problems, challenges, opportunities, well clinical translational issues faced

Язык: Английский

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