Advancements in the Application of Nanomedicine in Alzheimer’s Disease: A Therapeutic Perspective

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(18), С. 14044 - 14044

Опубликована: Сен. 13, 2023

Alzheimer’s disease (AD) is a progressive neurodegenerative that affects most people worldwide. AD complex central nervous system disorder. Several drugs have been designed to cure AD, but with low success rates. Because the blood–brain and blood–cerebrospinal fluid barriers are two protect system, their presence has severely restricted efficacy of many treatments studied for diagnosis and/or therapy. The use nanoparticles treatment focus an established rapidly developing field nanomedicine. Recent developments in nanomedicine made it possible effectively transport brain. However, numerous obstacles remain successful nanomedicines clinical settings treatment. Furthermore, given rapid advancement therapeutics, better outcomes patients can be anticipated. This article provides overview recent using different types management AD.

Язык: Английский

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Immunopotentiating Activity of Fucoidans and Relevance to Cancer Immunotherapy

Marine Drugs, Год журнала: 2023, Номер 21(2), С. 128 - 128

Опубликована: Фев. 15, 2023

Fucoidans, discovered in 1913, are fucose-rich sulfated polysaccharides extracted mainly from brown seaweed. These versatile and nontoxic marine-origin heteropolysaccharides have a wide range of favorable biological activities, including antitumor, immunomodulatory, antiviral, antithrombotic, anticoagulant, antioxidant, lipid-lowering activities. In the early 1980s, fucoidans were first recognized for their role supporting immune response later, 1990s, effects on potentiation began to emerge. recent years, understanding immunomodulatory fucoidan has expanded significantly. The ability fucoidan(s) activate CTL-mediated cytotoxicity against cancer cells, strong antitumor property, robust safety profile make desirable effective immunotherapy. This review focusses current progress immunopotentiation activity various fucoidans, emphasizing relevance Here, we will discuss action different cells how can be used as adjuvants conjunction with immunotherapeutic products improve treatment clinical outcome. Some key rationales possible combination immunotherapy discussed. An update is provided human studies available registered trials using while highlighting future prospects challenges.

Язык: Английский

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Low-intensity focused ultrasound targeted microbubble destruction reduces tumor blood supply and sensitizes anti-PD-L1 immunotherapy

Frontiers in Bioengineering and Biotechnology, Год журнала: 2023, Номер 11

Опубликована: Апрель 17, 2023

Immune checkpoint blockade (ICB) typified by anti-PD-1/PD-L1 antibodies as a revolutionary treatment for solid malignancies has been limited to subset of patients due poor immunogenicity and inadequate T cell infiltration. Unfortunately, no effective strategies combined with ICB therapy are available overcome low therapeutic efficiency severe side effects. Ultrasound-targeted microbubble destruction (UTMD) is an safe technique holding the promise decrease tumor blood perfusion activate anti-tumor immune response based on cavitation effect. Herein, we demonstrated novel combinatorial modality combining low-intensity focused ultrasound-targeted (LIFU-TMD) PD-L1 blockade. LIFU-TMD caused rupture abnormal vessels deplete induced microenvironment (TME) transformation sensitize anti-PD-L1 immunotherapy, which markedly inhibited 4T1 breast cancer's growth in mice. We discovered immunogenic death (ICD) portion cells effect from LIFU-TMD, characterized increased expression calreticulin (CRT) surface. Additionally, flow cytometry revealed substantially higher levels dendritic (DCs) CD8+ draining lymph nodes tissue, pro-inflammatory molecules like IL-12 TNF-α. These suggest that simple, effective, option provides clinically translatable strategy enhancing therapy.

Язык: Английский

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Functionalized biomimetic nanoparticles combining programmed death-1/programmed death-ligand 1 blockade with photothermal ablation for enhanced colorectal cancer immunotherapy

Acta Biomaterialia, Год журнала: 2022, Номер 157, С. 451 - 466

Опубликована: Ноя. 25, 2022

Immune checkpoint blockade therapy targeting programmed death-1 (PD-1) or its major ligand death-ligand 1 (PD-L1) has achieved remarkable success in the treatment of several tumors, including colorectal cancer. However, efficacy PD-1/PD-L1 inhibitors is limited some cancers within immunosuppressive tumor microenvironment (such as when there a lack immune cell infiltration). Herein, anti-PD-L1 functionalized biomimetic polydopamine-modified gold nanostar nanoparticles (PDA/[email protected] NPs) were developed for synergistic anti-tumor by combining with photothermal ablation. PDA/[email NPs prepared encapsulating (polydopamine-modified nanostar, PDA-GNS) membrane isolated from single-chain variable fragment (scFv) over-expressing cells. In addition to disrupting signals, scFv on was conducive accumulation PDA-GNS at sites. Importantly, ablation induced could reverse microenvironment, thereby further improving efficiency therapy. this study, synthetized exhibited good biocompatibility, efficient conversion ability, and enhanced tumor-targeting ability. vivo studies revealed that NP-based therapeutic strategy significantly inhibited growth, prolonged overall survival promoting maturation dendritic cells (DCs), increasing infiltration CD8+T cells, decreasing number regulatory T myeloid-derived suppressive cells). Collectively, combines ablation, which remodel effective clinical cancer Immunosuppressive main challenge facing death-1/programmed (PD-1/PD-L1) By fragment, we constructed NPs). specific binding PD-L1 present disrupt immunosuppression signaling, effectively deliver Additionally, PDA-GNS-mediated local tumors promoted release tumor-associated antigens thus activated responses. Meanwhile, hyperthermia facilitates vascular permeability. Therefore, sensitize remodeling provides new treatment.

Язык: Английский

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Photothermal therapy of copper incorporated nanomaterials for biomedicine

Biomaterials Research, Год журнала: 2023, Номер 27(1)

Опубликована: Фев. 9, 2023

Studies have reported on the significance of copper incorporated nanomaterials (CINMs) in cancer theranostics and tissue regeneration. Given their unique physicochemical properties tunable nanostructures, CINMs are used photothermal therapy (PTT) photothermal-derived combination therapies. They potential to overcome challenges unsatisfactory efficacy conventional therapies an efficient non-invasive manner. This review summarizes recent advances CINMs-based PTT biomedicine. First, classification structure introduced. tumors guided by multiple imaging modalities then reviewed. Various representative designs bone, skin other organs presented. Furthermore, biosafety is discussed. Finally, this analysis delves into current that researchers face offers optimistic outlook prospects clinical translational research field. aims at elucidating applications derived biomedicine encourage future design translation.

Язык: Английский

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Engineered Extracellular Vesicles Expressing Siglec‐10 Camouflaged AIE Photosensitizer to Reprogram Macrophages to Active M1 Phenotype and Present Tumor‐Associated Antigens for Photodynamic Immunotherapy

Small, Год журнала: 2023, Номер 20(12)

Опубликована: Ноя. 8, 2023

Abstract Cancer immunotherapy has attracted considerable attention due to its advantages of persistence, targeting, and ability kill tumor cells. However, the efficacy in practical applications is limited by heterogeneity complex immunosuppressive microenvironments which abundant M2 macrophages immune checkpoints (ICs) are present. Herein, two type‐I aggregation‐induced emission (AIE)‐active photosensitizers with various reactive oxygen species (ROS)‐generating efficiencies designed synthesized. Engineered extracellular vesicles (EVs) that express ICs Siglec‐10 first obtained from 4T1 The engineered EVs then fused AIE photosensitizer‐loaded lipidic nanosystem form SEx@Fc‐NPs. ROS generated inner photosensitizer SEx@Fc‐NPs through photodynamic therapy (PDT) can convert into M1 improve microenvironment. outer EV‐antigens carry tumor‐associated antigens directly stimulate dendritic cells maturation activate different types tumor‐specific T overcoming heterogeneity. In addition, blocking reversed macrophage exhaustion for enhanced antitumor ability. This study presents a combination PDT, checkpoints, greatly efficiency expected serve as an emerging strategy microenvironment overcome escape.

Язык: Английский

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How to optimize the immune checkpoint blockade therapy for cancers?

ONCOLOGIE, Год журнала: 2024, Номер 26(3), С. 343 - 348

Опубликована: Март 16, 2024

Abstract The realm of cancer therapy has been profoundly altered with the emergence immune checkpoint blockade (ICB) therapy, providing improved survival prospects for many patients some cancers. However, challenge achieving efficient or sustained therapeutic benefits underscores critical imperative to optimize ICB strategies. This review elucidates pivotal role predictive biomarkers in optimizing precision deciphering intricate dynamics associated response heterogeneity. Furthermore, it critically examines application nanotechnology-driven drug delivery as a promising avenue amplify efficacy, facilitating controlled and targeted release. Recognizing comprehensive dynamic interplay among tumor cells, stromal cells catalyzed transformative advances reverse translational research. approach enables researchers gain insights into underlying mechanisms responses, resistance mechanisms. convergence biomarkers, revolutionary nanotechnology, research emerges an indispensable focal point, propelling frontiers oncology within complex landscape therapy.

Язык: Английский

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Targeting tumor microenvironment with photodynamic nanomedicine

Medicinal Research Reviews, Год журнала: 2024, Номер unknown

Опубликована: Авг. 16, 2024

Photodynamic therapy (PDT) is approved for the treatment of certain cancers and precancer lesions. While early Photosensitizers (PS) have found their way to clinic, research in last two decades has led development third-generation PS, including photodynamic nanomedicine improved tumor delivery minimal systemic or phototoxicity. In terms nanoparticle design PDT, we are witnessing a shift from passive active outcomes with reduced PS dosage. Tumor microenvironment (TME) comprises complex dynamic landscape myriad potential targets nanocarriers that surface-modified ligands. Herein, review ways improvise PDT by actively targeting nanoparticles (NPs) intracellular organelles such as mitochondria lysosomes so forth, overcoming limitations caused PDT-induced hypoxia, disrupting blood vascular networks tissues-vascular targeted (VTP) immune cells photoimmunotherapy. We propose synergistic outlook will help address challenges deep-seated tumors, metastasis, relapse would lead robust response patients.

Язык: Английский

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Nuclear translocation of plasma membrane protein ADCY7 potentiates T cell-mediated antitumour immunity in HCC

Gut, Год журнала: 2024, Номер 74(1), С. 128 - 140

Опубликована: Сен. 30, 2024

Background The potency of T cell-mediated responses is a determinant immunotherapy effectiveness in treating malignancies; however, the clinical efficacy T-cell therapies has been limited hepatocellular carcinoma (HCC) owing to extensive immunosuppressive microenvironment. Objective Here, we aimed investigate key genes contributing immune escape HCC and raise new therapeutic strategy for remoulding Design genome-wide vivo clustered regularly interspaced short palindromic repeats (CRISPR) screen library was conducted identify associated with tolerance. Single-cell RNA-seq (scRNA-seq), flow cytometry, mouse models, chromatin immunoprecipitation coimmunoprecipitation were used explore function mechanism adenylate cyclase 7 (ADCY7) surveillance. Results CRISPR identified novel modulator-ADCY7. transmembrane protein ADCY7 undergoes subcellular translocation via caveolae-mediated endocytosis then translocates nucleus help leucine-rich repeat-containing 59 (LRRC59) karyopherin subunit beta 1 (KPNB1). In nucleus, it functions as transcription cofactor CCAAT/enhancer binding alpha (CEBPA) induce CCL5 transcription, thereby increasing CD8 + cell infiltration restrain progression. Furthermore, can be secreted exosomes enter neighbouring tumour cells promote induction. Exosomes high levels intratumoural suppress growth. Conclusion We delineate unconventional location ADCY7, highlighting its pivotal role immunity potential promising treatment target.

Язык: Английский

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Effective design of therapeutic nanovaccines based on tumor neoantigens

Journal of Controlled Release, Год журнала: 2025, Номер 380, С. 17 - 35

Опубликована: Фев. 3, 2025

Язык: Английский

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