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剂型对克服肿瘤乏氧的固体氧捕获材料的影响。

Impact of formulation on solid oxygen-entrapping materials to overcome tumor hypoxia.

机构信息

Department of Radiation Oncology, University of Iowa, Iowa City, Iowa, USA.

Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, USA.

出版信息

J Biomed Mater Res A. 2024 Jun;112(6):931-940. doi: 10.1002/jbm.a.37671. Epub 2024 Jan 17.

Abstract

Tumor hypoxia, resulting from rapid tumor growth and aberrant vascular proliferation, exacerbates tumor aggressiveness and resistance to treatments like radiation and chemotherapy. To increase tumor oxygenation, we developed solid oxygen gas-entrapping materials (O-GeMs), which were modeled after clinical brachytherapy implants, for direct tumor implantation. The objective of this study was to investigate the impact different formulations of solid O-GeMs have on the entrapment and delivery of oxygen. Using a Parr reactor, we fabricated solid O-GeMs using carbohydrate-based formulations used in the confectionary industry. In evaluating solid O-GeMs manufactured from different sugars, the sucrose-containing formulation exhibited the highest oxygen concentration at 1 mg/g, as well as the fastest dissolution rate. The addition of a surface coating to the solid O-GeMs, especially polycaprolactone, effectively prolonged the dissolution of the solid O-GeMs. In vivo evaluation confirmed robust insertion and positioning of O-GeMs in a malignant peripheral nerve sheath tumor, highlighting potential clinical applications.

摘要

肿瘤缺氧是由肿瘤的快速生长和血管异常增殖引起的,它加剧了肿瘤的侵袭性和对放疗、化疗等治疗的耐药性。为了增加肿瘤的氧合作用,我们根据临床近距离放射治疗植入物的原理,开发了用于直接肿瘤植入的固体氧气体捕获材料 (O-GeMs)。本研究的目的是研究不同配方的固体 O-GeMs 对氧的捕获和输送的影响。我们使用 Parr 反应堆,使用糖果工业中使用的基于碳水化合物的配方来制造固体 O-GeMs。在评估由不同糖制成的固体 O-GeMs 时,含有蔗糖的配方在 1mg/g 时表现出最高的氧浓度,以及最快的溶解速度。在固体 O-GeMs 表面涂覆一层物质,特别是聚己内酯,可以有效地延长固体 O-GeMs 的溶解时间。体内评估证实了 O-GeMs 在恶性外周神经鞘瘤中的稳健插入和定位,突出了其潜在的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/10984782/3f655e8610e5/nihms-1957739-f0001.jpg

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