Immune-theranostic gold nanorod-based NIR-responsive nanomedicine for the delivery of TLR7/8 adjuvant-induced effective anticancer therapy

Karunanidhi Gowsalya, Babu Rithisa, Selvaraj Shyamsivappan and Raju Vivek
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Abstract

Presently, there are several challenges that need to be overcome in the development of treatments that can effectively inhibit tumor growth, prevent the spread of tumor metastases, and protect the host against recurrence. Accordingly, a powerful synergistic immunotherapy method was developed to achieve the treatment of cancer. Herein, we established an improvement in the nanoengineering of gold nanorod (GNR)-mediated photothermal therapy (PTT) with theranostic indocyanine green (ICG), which also produced heat for effective PTT under near-infrared (NIR) light. Furthermore, co-encapsulated resiquimod (R848) induced the activation of an immune response against the tumor. In addition, a nuclear-targeted transactivator of transcription (TAT) peptide conjugated with FA-functionalized GNRs was produced for intranuclear tumor-targeted in vivo photothermal therapeutic efficacy, inducing DAMPs for immunogenic cell death (ICD). Post-PTT release of R848-activated TLR7/8 is essential for the development of a potent antitumor immune response by increasing the number of T cells, which recognize and kill tumors. Thus, this integrated immunotherapy method can be utilized for both the diagnosis and treatment of tumor recurrence, providing novel opportunities for both basic and clinical research. Collectively, our findings suggest that nanotechnology may be a useful technique for improving the efficacy of vaccine-based cancer immunotherapy.

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基于免疫theranostic金纳米棒的近红外响应纳米药物,用于传递TLR7/8佐剂诱导的有效抗癌疗法
目前,在开发能有效抑制肿瘤生长、防止肿瘤转移扩散和保护宿主免受复发的治疗方法方面,有几个难题需要克服。因此,一种强大的协同免疫疗法方法应运而生,以实现对癌症的治疗。在本文中,我们改进了金纳米棒(GNR)介导的光热疗法(PTT)的纳米工程,并加入了治疗性吲哚青绿(ICG),在近红外(NIR)光下也能产生热量,从而实现有效的光热疗法。此外,共同封装的雷喹莫德(R848)可诱导激活针对肿瘤的免疫反应。此外,一种核靶向转录激活因子(TAT)多肽与 FA 功能化 GNRs 共轭,用于核内肿瘤靶向体内光热疗效,诱导免疫原性细胞死亡(ICD)的 DAMPs。PTT后释放的R848激活的TLR7/8对于通过增加识别和杀死肿瘤的T细胞数量来形成有效的抗肿瘤免疫反应至关重要。因此,这种综合免疫疗法可用于肿瘤复发的诊断和治疗,为基础和临床研究提供了新的机遇。总之,我们的研究结果表明,纳米技术可能是提高基于疫苗的癌症免疫疗法疗效的有用技术。
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