Combined Core Stability and Degradability of Nanomedicine via Amorphous PDLLA-Dextran Bottlebrush Copolymer for Alzheimer’s Disease Combination Treatment,ACS Applied Materials & Interfaces

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Combined Core Stability and Degradability of Nanomedicine via Amorphous PDLLA-Dextran Bottlebrush Copolymer for Alzheimer’s Disease Combination Treatment
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2023-05-25 , DOI: 10.1021/acsami.3c03174
Fengying Dai ₁ , Xinpo Li ₁ , Kepeng Lv ₁ , Jing Wang ₂ , Yiping Zhao ₁

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Nanomedicine faces the challenges of infinite dilution, shear force, biological protein, or electrolyte competition. However, core cross-linking leads to biodegradability deficiency and brings inevitable side effects of nanomedicine on normal tissues. In order to overcome this bottleneck problem, we turn to amorphous poly(d,l)lactic acid (PDLLA)-dextran bottlebrush to emphasize the core stability of nanoparticles, and the amorphous structure offers an additional advantage of fast degradation property over the crystalline PLLA polymer. The graft density and side chain length of amorphous PDLLA together played important influence roles in controlling the architecture of nanoparticles. This effort produces structure-abundant particles, including micelles, vesicles, and large compound vesicles after self-assembly. Here, the amorphous bottlebrush PDLLA was verified to play a beneficial role in the structure stability and degradability of nanomedicines. The codelivery of the hydrophilic antioxidant of citric acid (CA), vitamin C (V_C), and gallic acid (GA) via the optimum nanomedicines could effectively repair the SH-SY5Y cell damage caused by H₂O₂. The CA/V_C/GA combination treatment repaired the neuronal function efficiently, and the cognitive abilities of senescence-accelerated mouse prone 8 (SAMP8) recovered.

中文翻译：

通过无定形 PDLLA-葡聚糖洗瓶刷共聚物结合纳米药物的核心稳定性和可降解性用于阿尔茨海默病联合治疗

纳米医学面临着无限稀释、剪切力、生物蛋白质或电解质竞争的挑战。然而，核心交联导致生物降解性不足，并带来纳米药物对正常组织不可避免的副作用。为了克服这个瓶颈问题，我们转向非晶聚（d，l)乳酸 (PDLLA)-dextran bottlebrush 强调纳米颗粒的核心稳定性，非晶结构提供了比结晶 PLLA 聚合物快速降解性能的额外优势。非晶PDLLA的接枝密度和侧链长度共同对控制纳米粒子的结构起着重要的影响作用。这种努力产生了结构丰富的颗粒，包括胶束、囊泡和自组装后的大复合囊泡。在这里，无定形瓶刷 PDLLA 被证实在纳米药物的结构稳定性和可降解性中发挥有益作用。柠檬酸 (CA)、维生素 C (V _C_{)和没食子酸(GA)通过优化的纳米药物可有效修复H 2} O ₂引起的SH-SY5Y细胞损伤。CA/V _C /GA 联合治疗有效修复了神经元功能，衰老加速小鼠 prone 8 (SAMP8) 的认知能力得以恢复。

更新日期：2023-05-25

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