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磁场/pH 驱动热化疗防治乳腺癌术后复发的非磁性高渗盐水基植入物

Nonmagnetic Hypertonic Saline-Based Implant for Breast Cancer Postsurgical Recurrence Prevention by Magnetic Field/pH-Driven Thermochemotherapy.

机构信息

Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science , Northwest University , Xi'an , Shaanxi 710069 , China.

Beijing Laboratory of Biomedical Materials , Beijing University of Chemical Technology , Beijing 100029 , China.

出版信息

ACS Appl Mater Interfaces. 2019 Mar 20;11(11):10597-10607. doi: 10.1021/acsami.9b02013. Epub 2019 Mar 6.

Abstract

Magnetic-mediated hyperthermia (MMT) is emerging as one of the promising techniques, which could synergistically treat cancer along with current treatment techniques such as chemotherapy and radiotherapy and trigger on-demand release of therapeutic macromolecules. However, the low specific absorption rate and potential in vivo toxicity of magnetic nanomaterials as the MMT mediators restrict the new advancements in MMT treatment. Herein, for the first trial, the unique inductive heating property of hypertonic saline (HTS), a clinically applied solution exhibiting several physiological effects under alternative magnetic field (AMF), was systematically investigated. Though without magnetic property, due to the dipolar polarization under the electromagnetic radiation, HTS can induce enough high and rapid temperature increase upon exposure under AMF. Based on such an observation, PEG-based HTS hydrogel was fabricated for the inhibition of unwanted diffusion of ions so as to ensure the ideal temperature rise at the targeted region for a longer time. Furthermore, an anticancer drug (doxorubicin) was also incorporated into the hydrogel to achieve the magnetic field/pH stimuli-responsive drug-sustainable release as well as synergistic thermochemotherapy. The potential application of the drug-loaded HTS-PEG-injectable hydrogel for breast cancer postsurgical recurrence prevention is demonstrated. Significant in vivo suppression of two kinds of breast cancer models was achieved by the hybrid hydrogel system. This work explores a new biomedical use of clinical HTS and a promising cancer treatment protocol based on HTS-PEG hydrogel for magnetic hyperthermia combined with stimuli-responsive chemotherapy for breast cancer postsurgical recurrence prevention.

摘要

磁介热疗(MMT)作为一种很有前途的技术正在兴起,它可以与化疗、放疗等现有治疗技术协同治疗癌症,并触发治疗性大分子的按需释放。然而,作为 MMT 介质的磁性纳米材料的低特异性吸收率和潜在的体内毒性限制了 MMT 治疗的新进展。在此,首次尝试系统研究了高渗盐水(HTS)的独特感应加热特性,HTS 是一种临床应用的溶液,在交变磁场(AMF)下具有多种生理效应。尽管 HTS 没有磁性,但由于在电磁辐射下的偶极子极化,它在 AMF 暴露下可以引起足够高和快速的温度升高。基于这一观察结果,制备了基于 PEG 的 HTS 水凝胶,以抑制离子的不必要扩散,从而确保在靶向区域长时间保持理想的升温。此外,还将一种抗癌药物(阿霉素)掺入水凝胶中,以实现磁场/pH 刺激响应性药物可持续释放以及协同热化疗。展示了载药 HTS-PEG 可注射水凝胶在乳腺癌术后复发预防中的潜在应用。该混合水凝胶系统在两种乳腺癌模型中均实现了显著的体内抑制。这项工作探索了临床 HTS 的新的生物医学用途,以及基于 HTS-PEG 水凝胶的 MMT 联合刺激响应化疗用于乳腺癌术后复发预防的有前途的癌症治疗方案。

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