Microneedle Patch Delivery of PROTACs for Anti-Cancer Therapy

ACS Nano, Год журнала: 2023, Номер 17(12), С. 11855 - 11868

Опубликована: Июнь 9, 2023

Proteolysis-targeting chimera (PROTAC) is an emerging technique for degrading disease-related proteins. However, the current PROTACs suffer from inadequate solubility and lack of organ targeting, which has hampered their druggability. Herein, we report direct sustained delivery using microneedle patches to diseased tissues. In this study, use estrogen receptor alpha (ERα)-degrading PROTAC, ERD308, treat ER-positive breast cancer. A pH-sensitive micelle, MPEG-poly(β-amino ester) (MPEG-PAE), used encapsulate ERD308 along with FDA-approved CDK4/6 inhibitor, Palbociclib (Pal), before loading into biodegradable patches. These enable prolonged drug release deep tumors, maintaining therapeutic levels at least 4 days, excellent retention rate over 87% in tumors. released can sufficiently degrade ERα MCF7 cells. Co-administration exhibits efficacy by 80% tumor reduction as well a good safety profile. Our work demonstrates feasibility proof-of-concept potential directly deliver

Язык: Английский

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Engineering multifunctional dynamic hydrogel for biomedical and tissue regenerative applications

Chemical Engineering Journal, Год журнала: 2024, Номер 487, С. 150403 - 150403

Опубликована: Март 16, 2024

Hydrogels have emerged in various biomedical applications, including tissue engineering and medical devices, due to their ability imitate the natural extracellular matrix (ECM) of tissues. However, conventional static hydrogels lack dynamically respond changes surroundings withstand robust biophysical microenvironment trigger on-demand functionality such as drug release mechanical change. In contrast, multifunctional dynamic can adapt external stimuli drawn great attention recent studies. It is realized that integration nanomaterials into provides numerous functionalities for a variety applications cannot be achieved by hydrogels. This review article comprehensive overview advances designing fabricating applications. We describe different types based on breakable reversible covalent bonds well noncovalent interactions. These mechanisms are described detail useful reference crosslinking strategies strongly influence properties also discuss use potential benefits. further explores nanocomposite hydrogels, delivery, engineering, bioadhesives, wound healing, cancer treatment, mechanistic study, multiple-scale Finally, we challenges future perspectives field diverse technologies.

Язык: Английский

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Inflammation‐Responsive Cell Membrane‐Camouflaged Nanoparticles against Liver Fibrosis via Regulating Endoplasmic Reticulum Stress and Oxidative Stress

Advanced Materials, Год журнала: 2024, Номер 36(19)

Опубликована: Фев. 19, 2024

Abstract Liver fibrosis represents a reversible stage of various chronic liver diseases that progresses to cirrhosis. This condition is characterized by an imbalance between tissue damage and repair, the production fibers in exceeds their degradation. Oxidative stress (OS) resulting from injury endoplasmic reticulum (ERS) triggered overproduction proteins are pivotal factors fibrosis. Melatonin demonstrates capability neutralize free radicals, shielding cells oxidative harm. It also specific inhibitor ERS receptor transcription activating factor 6 (ATF6), indicating its great potential ameliorating However, limited water solubility oral bioavailability under 15% present hurdles achieving therapeutic blood concentrations for treating The PLGA@Melatonin constructed loading melatonin with poly (lactic‐co‐glycolic acid) (PLGA). Platelet membranes (PM) activated hepatic stellate cell (HSCM) high expression platelet‐derived growth (PDGFR) extracted successfully construct PM@PLGA@Melatonin HSCM@PLGA@Melatonin, which subsequently utilized treat mice results illustrated remarkable effects two nanoparticles on fibrosis, along excellent targeting biosafety properties.

Язык: Английский

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Nano-PROTACs: state of the art and perspectives

Nanoscale, Год журнала: 2024, Номер 16(9), С. 4378 - 4391

Опубликована: Янв. 1, 2024

Schematic illustration of the combinational strategy nanotechnology and PROTACs (Nano-PROTACs): typical shortcomings traditional nanotechnology-based strategies for PROTAC drugs optimization.

Язык: Английский

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Cancer cell membrane-coated nanoparticles: a promising anti-tumor bionic platform

RSC Advances, Год журнала: 2024, Номер 14(15), С. 10608 - 10637

Опубликована: Янв. 1, 2024

This review summarized the function of cancer cell membranes and comprehensively discussed preparation membrane-coated nanoparticles (CCM-NPs) their application in anti-tumor therapy. The graphical abstract figure was drawn by Figdraw (https://www.figdraw.com).

Язык: Английский

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Double‐Network DNA Macroporous Hydrogel Enables Aptamer‐Directed Cell Recruitment to Accelerate Bone Healing

Advanced Science, Год журнала: 2023, Номер 11(1)

Опубликована: Ноя. 10, 2023

Abstract Recruiting endogenous bone marrow mesenchymal stem cells (BMSCs) in vivo to defect sites shows great promise cell therapies for tissue engineering, which tackles the shortcomings of delivering exogenous cells, including limited sources, low retention, stemness loss, and immunogenicity. However, it remains challenging efficiently recruit while simultaneously directing differentiation dynamic microenvironment promoting neo‐regenerated ingrowth achieve augmented regeneration. Herein, a synthetic macroporous double‐network hydrogel presenting nucleic acid aptamer nano‐inducer enhances BMSCs recruitment, osteogenic is demonstrated. An air‐in‐water template enables rapid construction highly interconnective structures, physical self‐assembly DNA strands chemical cross‐linking gelatin chains synergistically generate resilient double network. The Apt19S black phosphorus nanosheets‐specific demonstrate efficient differentiation, extracellular matrix mineralization. Notably, enhanced calvarial healing with promising mineralization new formation accompanied by adapting this engineered defects. findings suggest an appealing material approach overcoming traditional limitations cell‐delivery therapy that can inspire future design next‐generation

Язык: Английский

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Injectable smart stimuli-responsive hydrogels: pioneering advancements in biomedical applications

Biomaterials Science, Год журнала: 2023, Номер 12(1), С. 8 - 56

Опубликована: Окт. 25, 2023

Hydrogels have established their significance as prominent biomaterials within the realm of biomedical research. However, injectable hydrogels garnered greater attention compared with conventional counterparts due to excellent minimally invasive nature and adaptive behavior post-injection. With rapid advancement emerging chemistry deepened understanding biological processes, contemporary been endowed an "intelligent" capacity respond various endogenous/exogenous stimuli (such temperature, pH, light magnetic field). This innovation has spearheaded revolutionary transformations across fields such tissue engineering repair, controlled drug delivery, disease-responsive therapies, beyond. In this review, we comprehensively expound upon raw materials (including natural synthetic materials) principles these advanced hydrogels, concurrently providing a detailed discussion prevalent strategies for conferring stimulus responsiveness. Finally, elucidate latest applications "smart" stimuli-responsive in domain, offering insights into prospects.

Язык: Английский

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Enhancing cancer immunotherapy: Nanotechnology-mediated immunotherapy overcoming immunosuppression

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(9), С. 3834 - 3854

Опубликована: Июнь 3, 2024

Immunotherapy is an important cancer treatment method that offers hope for curing patients. While immunotherapy has achieved initial success, a major obstacle to its widespread adoption the inability benefit majority of The success or failure closely linked tumor's immune microenvironment. Recently, there been significant attention on strategies regulate tumor microenvironment in order stimulate anti-tumor responses immunotherapy. distinctive physical properties and design flexibility nanomedicines have extensively utilized target cells (including tumor-associated macrophages (TAMs), T cells, myeloid-derived suppressor (MDSCs), fibroblasts (TAFs)), offering promising advancements In this article, we reviewed aimed at targeting various focus models are based nanomedicines, with goal inducing enhancing improve It worth noting combining other treatments, such as chemotherapy, radiotherapy, photodynamic therapy, can maximize therapeutic effects. Finally, identified challenges nanotechnology-mediated needs overcome more effective nanosystems.

Язык: Английский

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Hydrogel-based platforms for site-specific doxorubicin release in cancer therapy

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Сен. 30, 2024

Язык: Английский

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Custom‐Design of Multi‐Stimuli‐Responsive Degradable Silica Nanoparticles for Advanced Cancer‐Specific Chemotherapy

Small, Год журнала: 2024, Номер 20(35)

Опубликована: Апрель 23, 2024

Chemotherapy is crucial in oncology for combating malignant tumors but often encounters obatacles such as severe adverse effects, drug resistance, and biocompatibility issues. The advantages of degradable silica nanoparticles tumor diagnosis treatment lie their ability to target delivery, minimizing toxicity normal tissues while enhancing therapeutic efficacy. Moreover, responsiveness both endogenous exogenous stimuli opens up new possibilities integrating multiple modalities. This review scrutinizes the burgeoning utility combination with chemotherapy other Commencing elucidation synthesis degradation mechanisms, emphasis placed on these materials (e.g., pH, redox reactions, hypoxia, enzymes) light high-intensity focused ultrasound). this exploration delves into strategies harnessing alone, coupled radiotherapy, photothermal therapy, photodynamic gas immunotherapy, starvation chemodynamic elucidating multimodal synergies. Concluding an assessment advances, challenges, constraints oncology, despite hurdles, future investigations are anticipated augment role cancer therapy. These insights can serve a compass devising more efficacious combined strategies.

Язык: Английский

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