Self-Assembled Hybrid Nanogel as a Multifunctional Theranostic Probe for Enzyme-Regulated Ultrasound Imaging and Tumor Therapy,ACS Applied Bio Materials

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Self-Assembled Hybrid Nanogel as a Multifunctional Theranostic Probe for Enzyme-Regulated Ultrasound Imaging and Tumor Therapy
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2021-05-05 , DOI: 10.1021/acsabm.1c00079
Qing Wu ₁ , Qi Zhang ₂ , Tianyu Yu ₂ , Xia Wang ₂ , Chunping Jia ₃ , Zonghui Zhao ₁ , Jianlong Zhao ₃

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Multifunctional theranostic nanoprobes integrated with stimuli-responsive imaging and therapeutic capabilities have shown great potential to enhance the early cancer diagnostic efficacy and therapeutic efficiency. Elevated levels of lactate and hydrogen peroxide have been considered as the characteristic feature of the tumor microenvironment and can thus be exploited for developing promising theranostic strategies. We demonstrate here that the biocompatible and responsive enzyme-based nanogel probe has been designed as a promising theranostic tool to target high lactate and hydrogen peroxide for ultrasound imaging (US) and cancer treatment. We encapsulate the dual enzyme lactate oxidase (LOD) and catalase (CAT) into the self-assembled nanogels to fabricate responsive nanoprobe LOD/CAT-loaded nanogels (LCNGs). The nanoprobes can respond to the lactate and H₂O₂ rich tumor microenvironment to generate abundant oxygen, which further accumulates into microbubbles for enhanced US imaging. Besides, LCNGs@DOX has been further created by integrating the nanoprobes with doxorubicin (DOX) for cancer therapy. Both in vitro and in vivo results demonstrate enhanced US imaging and effective cell proliferation inhibition of LCNGs@DOX, allowing the preparation of safe and efficient theranostic nanoprobes capable of responsive US imaging and treating tumors.

中文翻译：

自组装混合纳米凝胶作为酶调节超声成像和肿瘤治疗的多功能治疗探针

与刺激响应成像和治疗能力相结合的多功能治疗诊断纳米探针已显示出提高早期癌症诊断功效和治疗效率的巨大潜力。乳酸和过氧化氢水平升高被认为是肿瘤微环境的特征，因此可用于开发有前景的治疗策略。我们在此证明，生物相容性和响应性酶基纳米凝胶探针已被设计为一种有前途的治疗诊断工具，可靶向用于超声成像（美国）和癌症治疗的高乳酸和过氧化氢。我们将双酶乳酸氧化酶 (LOD) 和过氧化氢酶 (CAT) 封装到自组装纳米凝胶中，以制造响应纳米探针 LOD/CAT 负载的纳米凝胶 (LCNG)。₂ O ₂丰富的肿瘤微环境以产生丰富的氧气，进一步积累成微泡以增强超声成像。此外，通过将纳米探针与多柔比星 (DOX) 相结合，进一步创建了 LCNGs@DOX，用于癌症治疗。体外和体内结果均表明 LCNGs@DOX 可增强超声成像和有效抑制细胞增殖，从而能够制备安全高效的治疗诊断纳米探针，能够响应超声成像和治疗肿瘤。

更新日期：2021-05-17

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