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1.
Sci Adv ; 10(33): eado3919, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39141742

RESUMO

Postoperative rehemorrhage following intracerebral hemorrhage surgery is intricately associated with a high mortality rate, yet there is now no effective clinical treatment. In this study, we developed a hemoglobin (Hb)-responsive in situ implantable DNA hydrogel comprising Hb aptamers cross-linked with two complementary chains and encapsulating deferoxamine mesylate (DFO). Functionally, the hydrogel generates signals upon postoperative rehemorrhage by capturing Hb, demonstrating a distinctive "self-diagnosis" capability. In addition, the ongoing capture of Hb mediates the gradual disintegration of the hydrogel, enabling the on-demand release of DFO without compromising physiological iron-dependent functions. This process achieves self-treatment by inhibiting the ferroptosis of neurocytes. In a collagenase and autologous blood injection model-induced mimic postoperative rehemorrhage model, the hydrogel exhibited a 5.58-fold increase in iron absorption efficiency, reducing hematoma size significantly (from 8.674 to 4.768 cubic millimeters). This innovative Hb-responsive DNA hydrogel not only offers a therapeutic intervention for postoperative rehemorrhage but also provides self-diagnosis feedback, holding notable promise for enhancing clinical outcomes.


Assuntos
Hemorragia Cerebral , Hemoglobinas , Hidrogéis , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/tratamento farmacológico , Hidrogéis/química , Hemoglobinas/metabolismo , Animais , Desferroxamina/farmacologia , Desferroxamina/uso terapêutico , Desferroxamina/química , DNA/metabolismo , Humanos , Masculino , Ratos , Modelos Animais de Doenças , Ferroptose/efeitos dos fármacos , Ferro/metabolismo , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/diagnóstico , Aptâmeros de Nucleotídeos/farmacologia , Aptâmeros de Nucleotídeos/química
2.
Adv Healthc Mater ; 12(12): e2203141, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36648020

RESUMO

Intracerebral hemorrhage (ICH) is the most devastating form of stroke, which accounts for 10-15% of cases and causes high morbidity and mortality. With the continuous exploration of the pathological mechanism of ICH, extensive research focusing on ICH therapy has been conducted. However, the traditional treatment methods, such as surgery for removing the hematoma and pharmacotherapy for improving the clearance of the hematoma and neuroprotection, are greatly limited due to their poor practicality and treatment efficiency. The rapid development of drug delivery systems offers an important prospect for treating ICH as they exhibit great versatility, which can improve the pharmacokinetic behavior of drugs in vivo, increase the drug accumulation in specific cell types or tissues, and enhance the therapeutic effect with diminished toxic effect. In this review, the main molecular pathological mechanisms of ICH are comprehensively described and the limitation of traditional pharmacotherapy are also discussed. Then the development based on drug delivery systems for treating ICH is highlighted. Finally, based on these discussions the challenges of drug delivery systems with a view to providing a new feasible path for the treatment of ICH are summarized.


Assuntos
Hemorragia Cerebral , Acidente Vascular Cerebral , Humanos , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/metabolismo , Sistemas de Liberação de Medicamentos , Hematoma/tratamento farmacológico , Hematoma/metabolismo
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