Intravesical In Situ Immunostimulatory Gel for Triple Therapy of Bladder Cancer,ACS Applied Materials & Interfaces

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Intravesical In Situ Immunostimulatory Gel for Triple Therapy of Bladder Cancer
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2020-11-25 , DOI: 10.1021/acsami.0c15176
Pengyu Guo _{1,

2,

3,

4} , Lu Wang _{1,

2,

3} , Wenting Shang ₄ , Jiuwei Chen _{1,

2,

3} , Ziyin Chen _{1,

2,

3} , Feng Xiong _{1,

2,

3} , Ziqi Wang _{1,

2,

3} , Zhichao Tong _{1,

2,

3} , Keliang Wang _{1,

2,

3} , Liming Yang ₅ , Jie Tian ₄ , Wanhai Xu _{1,

2,

3}

Affiliation

Bladder cancer displays multiple biological features aided in drug resistance; therefore, single therapy fails to induce complete tumor regression. To address this issue, various kinds of cell death of cancer cells as well as restoring tumor immune microenvironment need to be taken into consideration. Here, we introduce a gel system termed AuNRs&IONs@Gel, which target-delivers a combination of photothermal, ferroptotic, and immune therapy through intravesical instillation. AuNRs&IONs@Gel consists of a gel delivery platform, embedded gold nanorods (AuNRs), and iron oxide nanoparticles (IONs). The targeted delivery gel platform provides dextran aldehyde-selective adhesion with cancer collagen. In this condition, photothermal therapy can be performed by gold nanorods (AuNRs) under imaging-guided near-infrared radiation. Local high concentrations of IONs can be absorbed by cancer cell to induce ferroptosis. Moreover, tumor-associated macrophages which often display an immune-suppressive M2-like phenotype will be repolarized by IONs into the antitumor M1-like phenotype, exerting a direct antitumor effect and professional antigen presentation of dead cancer cells. This process triggers a potent immune response of innate and adapt immunities to protect tumor rechallenge in long terms. Our triple-therapy strategy employs FDA-approved nanoparticles to inhibit bladder cancer which may possess great potential for clinical translation.

中文翻译：

膀胱原位免疫刺激凝胶用于膀胱癌的三联疗法

膀胱癌显示出多种生物学特性，有助于耐药性；因此，单一疗法不能诱导肿瘤完全消退。为了解决这个问题，需要考虑癌细胞的各种细胞死亡以及恢复肿瘤免疫微环境。在这里，我们介绍了一种称为AuNRs＆IONs @ Gel的凝胶系统，该系统可通过膀胱内滴注来实现光热疗法，促铁疗法和免疫疗法的结合。AuNRs＆IONs @ Gel由凝胶递送平台，嵌入的金纳米棒（AuNRs）和氧化铁纳米颗粒（IONs）组成。靶向递送凝胶平台提供了与癌症胶原蛋白的葡聚糖醛选择性粘附。在这种情况下，可以通过金纳米棒（AuNR）在成像引导的近红外辐射下进行光热疗法。癌细胞可以吸收局部高浓度的IONs，从而引起肥大症。此外，通常会显示免疫抑制性M2样表型的肿瘤相关巨噬细胞将被IONs极化为抗肿瘤M1样表型，从而发挥直接的抗肿瘤作用和死细胞的专业抗原呈递。这个过程会触发先天性强免疫反应，并通过长期免疫来保护肿瘤再发。我们的三联疗法策略采用FDA批准的纳米颗粒抑制膀胱癌，这可能具有很大的临床翻译潜力。发挥直接的抗肿瘤作用和专业的死癌细胞抗原呈递功能。这个过程会触发先天性强免疫反应，并通过长期免疫来保护肿瘤再发。我们的三联疗法策略采用FDA批准的纳米颗粒抑制膀胱癌，这可能具有很大的临床翻译潜力。发挥直接的抗肿瘤作用和专业的死癌细胞抗原呈递功能。这个过程会触发先天性强免疫反应，并通过长期免疫来保护肿瘤再发。我们的三联疗法策略采用FDA批准的纳米颗粒抑制膀胱癌，这可能具有很大的临床翻译潜力。

更新日期：2020-11-25

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