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1.
Nanoscale ; 16(10): 5280-5293, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38369899

RESUMO

Macrophage-driven inflammation is the central player in a range of pathological conditions, comprising autoimmune disorders, various cancers, as well as chronic inflammatory states like rheumatoid arthritis. Therapeutic strategies tailored to specifically target macrophage behavior have acquired substantial interest for their potential to alleviate chronic inflammation effectively. In this study, we introduce a pioneering therapeutic approach utilizing specialized CD44-targeted immunoliposomes carrying bortezomib to address inflammation at the cellular level and the significance of this strategy lies in its precision nature. Bortezomib's inhibition of the proteasome interferes with the finely-tuned mechanism that controls NFκB activation, ultimately leading to a downregulation of the inflammatory response. After performing computational docking demonstrating its strong binding affinity to the proteasome molecule, the resulting nano-construct displayed a hydrodynamic size of 144.26 ± 74.4 nm and a quasi-spherical morphology. Moreover, the nano-construct ensured a minimum shelf-life of 30 days, aiming for targeted delivery with practical longevity. Upon internalization of immunoliposomes, the interaction with CD44 receptors exhibited downstream signaling events. This included the activation of Jun amino-terminal kinases 1/2 (JNK1/2) and the extracellular-signal-regulated kinases (ERK) pathway. JNK1/2 activation may lead to the release of mitochondrial pro-apoptotic factors, triggering the intrinsic apoptotic pathway and activation of caspases, which was confirmed from the level of apoptotic gene and protein expression. The precise targeting and anti-inflammatory action of this therapy against macrophages hold promise for therapeutic interventions in a wide range of inflammatory conditions, offering a novel avenue for precision medicine in the battle against excessive inflammation.


Assuntos
Inflamação , Complexo de Endopeptidases do Proteassoma , Humanos , Bortezomib/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Complexo de Endopeptidases do Proteassoma/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipossomos/metabolismo , Macrófagos/metabolismo , Receptores de Hialuronatos/metabolismo
2.
Life Sci ; 334: 122232, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37918626

RESUMO

Chronic wounds, burns, and surgical incisions represent critical healthcare challenges that significantly impact patient quality of life and strain healthcare resources. In response to these pressing needs, the field of wound healing has witnessed a radical advancement with the emergence of functional hydrogel-based dressings. This review article underscores the severity and importance of this transformative study in the domain of wound healing. The hydrogel matrix offers a moist and supportive environment that facilitates cellular migration, proliferation, and tissue regeneration, vital for efficient wound closure. Their conformable nature ensures patient comfort, reducing pain and uneasiness during dressing changes, particularly in chronic wounds where frequent interventions are required. Beyond their structural merits, functional hydrogel dressings possess the capability of incorporating bioactive molecules such as growth factors and antimicrobial agents. This facilitates targeted and sustained delivery of therapeutics directly to the wound site, addressing the multifactorial nature of chronic wounds and enhancing the healing trajectory. The integration of advanced nanotechnology has propelled the design of hydrogel dressings with enhanced mechanical strength and controlled drug release profiles, amplifying their therapeutic potential. In conclusion, the significance of this study lies in its ability to revolutionize wound healing practices and positively impact the lives of countless individuals suffering from chronic wounds and burns. As this transformative technology gains momentum, it holds the promise of addressing a major healthcare burden worldwide, thus heralding a new era in wound care management.


Assuntos
Queimaduras , Hidrogéis , Humanos , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Qualidade de Vida , Bandagens , Cicatrização , Queimaduras/tratamento farmacológico
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