Dendritic Polymer‐Based Nanomedicines Remodel the Tumor Stroma: Improve Drug Penetration and Enhance Antitumor Immune Response

Advanced Materials, Год журнала: 2024, Номер 36(25)

Опубликована: Март 12, 2024

Abstract The dense extracellular matrix (ECM) in solid tumors, contributed by cancer‐associated fibroblasts (CAFs), hinders penetration of drugs and diminishes their therapeutic outcomes. A sequential treatment strategy remodeling the ECM via a CAF modifier (dasatinib, DAS) is proposed to promote an immunogenic cell death (ICD) inducer (epirubicin, Epi) apoptotic vesicles, ultimately enhancing efficacy against breast cancer. Dendritic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA)‐based nanomedicines (poly[OEGMA‐Dendron(G2)‐Gly‐Phe‐Leu‐Gly‐DAS] (P‐DAS) poly[OEGMA‐Dendron(G2)‐hydrazone‐Epi] (P‐Epi)) are developed for delivery DAS Epi, respectively. P‐DAS reprograms CAFs reduce collagen downregulating anabolism energy metabolism, thereby reducing deposition. regulated can enhance tumor P‐Epi strengthen its ICD effect, leading amplified antitumor immune response. In cancer‐bearing mice, this approach alleviates barrier, resulting reduced burden increased cytotoxic T lymphocyte infiltration, more encouragingly, synergizes effectively with anti‐programmed 1 (PD‐1) therapy, significantly inhibiting growth preventing lung metastasis. Furthermore, systemic toxicity barely detectable after P‐Epi. This opens new avenue treating desmoplastic tumors metabolically targeting overcome barrier.

Язык: Английский

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Unravelling the potential of mitochondria-targeted liposomes for enhanced cancer treatment

Drug Discovery Today, Год журнала: 2023, Номер 29(1), С. 103819 - 103819

Опубликована: Ноя. 7, 2023

Язык: Английский

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Single-organelle localization-based super-resolution imaging for subcellular molecules micro-dynamics

Coordination Chemistry Reviews, Год журнала: 2024, Номер 504, С. 215670 - 215670

Опубликована: Янв. 13, 2024

Язык: Английский

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Unlocking the Mitochondria for Nanomedicine-based Treatments: Overcoming Biological Barriers, Improving Designs, and Selecting Verification Techniques

Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 207, С. 115195 - 115195

Опубликована: Фев. 5, 2024

Enhanced targeting approaches will support the treatment of diseases associated with dysfunctional mitochondria, which play critical roles in energy generation and cell survival. Obstacles to mitochondria-specific include presence distinct biological barriers need pass through (or avoid) various internalization mechanisms. A range studies have reported design mitochondrially-targeted nanomedicines that navigate complex routes required influence mitochondrial function; nonetheless, a significant journey lies ahead before become suitable for clinical use. Moving swiftly forward require safety studies, vivo assays confirming effectiveness, methodologies validate mitochondria-targeted nanomedicines' subcellular location/activity. From nanomedicine standpoint, we describe involved (from administration arrival within mitochondria), features influencing rational design, techniques used identify/validate successful targeting. Overall, rationally-designed mitochondria-targeted-based hold great promise precise therapeutic delivery.

Язык: Английский

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Precise subcellular targeting approaches for organelle-related disorders

Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 212, С. 115411 - 115411

Опубликована: Июль 19, 2024

Язык: Английский

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Intraneuronal Aβ accumulation causes tau hyperphosphorylation via endolysosomal leakage

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(3)

Опубликована: Март 1, 2025

Abstract INTRODUCTION Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) peptide plaques and intracellular neurofibrillary tangles formed hyperphosphorylated tau. Many attempts have been made to clarify the link between Aβ tau in pathogenesis, but conclusive data describing a pathway for this connection are still lacking. METHODS We developed neuronal model of Aβ‐induced toxicity studied downstream effects intraneuronal Aβ42 accumulation on hyperphosphorylation using confocal microscopy live cell imaging. RESULTS added medium was endocytosed into neurons, inducing formation endolysosomal protofibrils leakage, which turn promoted hyperphosphorylation. Asparaginyl endopeptidase (AEP) released from disrupted lysosomes, inhibition peptidase activity reduced DISCUSSION The suggest mechanism AD accumulates aggregates gradually neurons over time, leading leakage release AEP, subsequently triggers Highlights endocytosis leads its time. polymerizes causes leakage. Tau induced asparagine inhibited an inhibitor.

Язык: Английский

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Subcellular targeting strategies for protein and peptide delivery

Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 212, С. 115387 - 115387

Опубликована: Сен. 1, 2024

Язык: Английский

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Organelle Targeted Drug Delivery: Key Challenges, Recent Advancements and Therapeutic Implications

Endocrine Metabolic & Immune Disorders - Drug Targets, Год журнала: 2024, Номер 24(13), С. 1480 - 1487

Опубликована: Фев. 2, 2024

Organelle-specific targeted drug delivery has emerged as a promising approach in the field of and therapeutics. This innovative strategy involves precise therapeutic agents to specific organelles within cells, such nucleus, mitochondria, endoplasmic reticulum, or lysosomes, with aim enhancing efficacy while minimizing offtarget effects. Despite its tremendous potential, organelle-specific faces several key challenges. One major challenge is development systems that can accurately navigate complex intracellular environment deliver drugs exclusively desired organelles. Achieving this level precision demands advanced nanotechnology biomaterials engineering. Furthermore, ensuring safety biocompatibility these paramount. Recent advancements include nanocarriers, liposomes, nanoparticles, dendrimers, designed target through ligandreceptor interactions pH-responsive mechanisms. Additionally, molecular biology genetic engineering have enabled design genetically encoded organellespecific systems. The implications are vast. potential revolutionize treatment diseases organelle- pathologies, neurodegenerative disorders, cancer, mitochondrial diseases. By precisely targeting involved disease progression, therapies be significantly improved collateral damage healthy tissues.

Язык: Английский

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A Trackable Mitochondria-Targeting Nanosystem for Mitochondrial Redox and Mitophagy Regulation in Diabetic Retinopathy Management

Chemical Engineering Journal, Год журнала: 2025, Номер 505, С. 159618 - 159618

Опубликована: Янв. 15, 2025

Язык: Английский

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Green and sustainable separation processes for environmental and chemical engineering

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 457 - 479

Опубликована: Янв. 1, 2025

Язык: Английский

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