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载有葡萄糖氧化酶的胶体稳定 WS 纳米碗用于结直肠肿瘤的联合饥饿/光热治疗。

Glucose oxidase-loaded colloidal stable WS nanobowls for combined starvation/photothermal therapy of colorectal tumors.

机构信息

School of Materials and Chemistry, the University of Shanghai for Science and Technology, No. 516 Jungong Road, Shanghai 200093, PR China.

Department of Gastroenterology, Changhai Hospital, Naval Military Medical University, No. 168 Changhai Road, Shanghai 200433, PR China.

出版信息

Int J Pharm. 2023 Apr 5;636:122848. doi: 10.1016/j.ijpharm.2023.122848. Epub 2023 Mar 15.

Abstract

Glucose is used as an important nutrient to support cell growth. The glucose oxidase (GOx) can transform glucose into gluconic acid and toxic HO, which can be used for tumor starvation therapy. However, the leakage of GOx may cause severe side effects to the normal tissue. To prevent the accidental leakage of GOx, this study proposes the chemical modification of GOx on the photothermal transducing agent surface, to realize the safe and combined starvation and photothermal therapy of colorectal tumors. Polyvinylpyrrolidone (PVP)-modified WS nanobowls (WS-PVP) as a photothermal transducing agent were produced using a one-pot preparation method. Then, α-lipoic acid (LA) molecules were immobilized at the sulfur-deficient sites on the surface of WS nanobowls to afford the chemical loading of GOx through amide bonds. Under the irradiation of a near-infrared laser (808 nm), thermal energy is generated by WS to kill colorectal cancer cells locally. The photothermal conversion efficiency of WS-PVP-LA was 27.2%. This study is anticipated to open up an alternative avenue for the rational design of multifunctional nanotherapeutics for tumor therapy.

摘要

葡萄糖被用作支持细胞生长的重要营养物质。葡萄糖氧化酶(GOx)可以将葡萄糖转化为葡萄糖酸和有毒的 HO,可用于肿瘤饥饿治疗。然而,GOx 的泄漏可能会对正常组织造成严重的副作用。为了防止 GOx 的意外泄漏,本研究提出在光热转换剂表面对 GOx 进行化学修饰,以实现结直肠肿瘤的安全联合饥饿和光热治疗。通过一锅法制备了聚维酮(PVP)修饰的 WS 纳米碗(WS-PVP)作为光热转换剂。然后,通过酰胺键将巯基缺陷位点固定在 WS 纳米碗表面上的 α-硫辛酸(LA)分子,从而通过酰胺键实现 GOx 的化学负载。在近红外激光(808nm)的照射下,WS 产生热能,局部杀死结直肠癌细胞。WS-PVP-LA 的光热转换效率为 27.2%。本研究有望为肿瘤治疗的多功能纳米治疗药物的合理设计开辟一条新途径。

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