Wu Huayu, Zhong Dan, Zhang Zhijun, Wu Yahui, Li Yunkun, Mao Hongli, Luo Kui, Kong Deling, Gong Qiyong, Gu Zhongwei
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, P. R. China.
Huaxi MR Research Center (HMRRC) Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University, Chengdu 610041, P. R. China.
ACS Nano. 2021 Mar 23;15(3):4845-4860. doi: 10.1021/acsnano.0c09594. Epub 2021 Feb 24.
Morphology genetic biomedical materials (MGBMs), referring to fabricating materials by learning from the genetic morphologies and strategies of natural species, hold great potential for biomedical applications. Inspired by the cargo-carrying-bacterial therapy (microbots) for cancer treatment, a MGBM (artificial microbots, AMBs) was constructed. Rather than the inherent bacterial properties (cancerous chemotaxis, tumor invasion, cytotoxicity), AMBs also possessed ingenious nitric oxide (NO) generation strategy. Mimicking the bacterial construction, the hyaluronic acid (HA) polysaccharide was induced as a coating capsule of AMBs to achieve long circulation in blood and specific tissue preference (tumor tropism). Covered under the capsule-like polysaccharide was the combinatorial agent, the self-assembly constructed by the amphiphilic dendrons with abundant l-arginine residues peripherally (as endogenous NO donor) and hydrophobic chemotherapeutic drugs at the core stacking on the surface of SWNTs (the photothermal agent) for a robust chemo-photothermal therapy (chemo-PTT) and the elicited immune therapy. Subsequently, the classic inducible nitric oxide synthase (iNOS) pathway aroused by immune response was revolutionarily utilized to oxidize the l-arginine substrates for NO production, the process for which could also be promoted by the high reactive oxygen species level generated by chemo-PTT. The NO generated by AMBs was intended to regulate vasodilation and cause a dramatic invasion (as the microbots) to disperse the therapeutic agents throughout the solid tumor for a much more enhanced curative effect, which we defined as "self-propulsion". The self-propelled AMBs exhibiting impressive primary tumor ablation, as well as the distant metastasis regression to conquer the metastatic triple negative breast cancer, provided pioneering potential therapeutic opportunities, and enlightened broad prospects in biomedical application.
形态学遗传生物医学材料（MGBMs），是指通过借鉴天然物种的遗传形态和策略来制造材料，在生物医学应用中具有巨大潜力。受用于癌症治疗的载药细菌疗法（微型机器人）启发，构建了一种MGBM（人工微型机器人，AMB）。与细菌的固有特性（癌趋化性、肿瘤侵袭、细胞毒性）不同，AMB还拥有巧妙的一氧化氮（NO）生成策略。模仿细菌结构，诱导透明质酸（HA）多糖作为AMB的包衣胶囊，以实现血液中的长循环和特定的组织偏好（肿瘤靶向性）。在类似胶囊的多糖覆盖下的是组合剂，它由两亲性树枝状分子自组装而成，外周有丰富的L-精氨酸残基（作为内源性NO供体），核心是疏水性化疗药物，堆积在单壁碳纳米管（光热剂）表面，用于强大的化学-光热疗法（化学-PTT）和引发的免疫疗法。随后，免疫反应引发的经典诱导型一氧化氮合酶（iNOS）途径被创新性地用于氧化L-精氨酸底物以产生NO，化学-PTT产生的高活性氧水平也可促进这一过程。AMB产生的NO旨在调节血管舒张，并引发剧烈侵袭（如微型机器人），将治疗剂分散到实体瘤中，以增强治疗效果，我们将其定义为“自我推进”。自我推进的AMB在原发性肿瘤消融方面表现出色，同时对远处转移有消退作用，可攻克转移性三阴性乳腺癌，提供了开创性的潜在治疗机会，并为生物医学应用带来了广阔前景。
