聚合物材料抑制由胞外核酸引起的炎症和肿瘤转移

Polymers inhibit inflammation and tumor metastasis caused by extracellular nucleic acids

细胞死亡所释放的游离核酸引发了免疫细胞的异常激活,这一现象使机体组织受损,引发慢性或急性炎症反应,导致多种疾病,从而威胁生命.近几年,研究人员开始探索利用表面具有丰富功能化官能团聚合物材料与游离核酸相互作用,以抑制炎症反应、促进伤口愈合以及阻止肿瘤转移.本文概述了采用不同类型的功能化聚合物在抗炎和抗肿瘤等领域的研究进展.通过调控聚合物的表面官能团,精确地控制聚合物与核酸之间的相互作用,使其能够有效地捕获和降解游离核酸.例如:功能化树枝状聚合物、功能化聚合物纳米颗粒等材料有效抑制类风湿性关节炎和银屑病等自身免疫疾病;利用核酸清除功能化聚合物水凝胶有效促进糖尿病并发症中的伤口修复;设计合成具有良好生物安全性的功能化聚氨基酸材料破坏中性粒细胞胞外陷阱,有效抑制肿瘤转移.在此基础上,具有催化核酸水解功能的聚合物模拟酶可以更高效地降解游离核酸,抑制炎症反应.总的来说,利用功能化聚合物与游离核酸相互作用的策略,为多种疾病提供了新的治疗方案.未来的研究可以进一步调控聚合物的结构,为更多相关疾病的治疗提供新的思路和方法.

The liberation of free nucleic acids upon cell death serves as a critical biological event,triggering aberrant responses from the immune system.This cascade of events involves the release of cytokines by immune cells,which can lead to tissue damage,instigate acute or chronic inflammatory reactions,and precipitate the onset of various diseases,some of which can be life-threatening.Addressing the management of these free nucleic acids to prevent adverse immune reactions has emerged as a pressing challenge in biomedical research.In tackling this challenge,researchers have turned to the versatile properties of polymer materials,particularly the diverse functional groups present on their surfaces.These functional groups offer opportunities for interactions with nucleic acid molecules,enabling the orchestration of their activities in vivo.Through such interactions,inflammation can be modulated,wound healing can be expedited,and the metastasis of tumors can be impeded.Consequently,the application of functional polymers has garnered significant attention as a promising avenue for the treatment of various diseases.Our research group has made notable advancements in utilizing functional polymers for nucleic acid clearance,particularly in the context of autoimmune diseases.Rheumatoid arthritis,for instance,has been effectively attenuated through the application of functionalized dendrimers,showcasing the potential of polymer-based interventions in autoimmune conditions.Moreover,to address the challenge of limited retention time of materials at affected sites,we have engineered functional polymer nanoparticles.These nanoparticles undergo surface modifications aimed at mitigating toxicity while facilitating enhanced drug loading,thereby improving their therapeutic efficacy and applicability.Expanding the scope of our research,we have also explored the application of functional polymers in the treatment of psoriasis,a chronic autoimmune skin condition.Through meticulous optimization of particle size,we have achieved promising outcomes in terms of therapeutic efficacy,further underscoring the versatility and potential of functional polymer-based interventions in autoimmune diseases.In addition to direct interactions with nucleic acids,we have developed polymer-mimicking enzymes capable of degrading free nucleic acids in vivo.In contrast to the non-specific binding observed with functional polymers,these artificial nucleic acid hydrolases offer the advantage of complete degradation of free nucleic acids with lower toxicity.This novel approach expands the repertoire of polymer-based interventions in autoimmune disease management.Turning our focus to the realm of external injuries,we have leveraged functional polymer hydrogels to expedite the healing of diabetic wounds.Additionally,functional polymer nanovesicles have demonstrated promising results in accelerating recovery from traumatic brain injuries,highlighting their potential in diverse clinical applications beyond autoimmune diseases.In the context of cancer metastasis,our research efforts have centered on impeding the binding of neutrophil extracellular traps to cancer cell surface proteins using functionalized polyamino acid nanoparticles.This intervention has effectively curtailed cancer cell skeletal deformation and migration,significantly prolonging the survival duration of animals afflicted with cancer.In conclusion,the utilization of functional polymers represents a versatile and promising approach for the treatment of various diseases,including autoimmune conditions,external injuries,and cancer metastasis.Further research endeavors should aim to refine the design and application of these polymers,harnessing their full therapeutic potential to revolutionize disease management strategies and improve patient outcomes.