A Facile Low-Dose Photosensitizer-Incorporated Dissolving Microneedles-Based Composite System for Eliciting Antitumor Immunity and the Abscopal Effect
A Facile Low-Dose Photosensitizer-Incorporated Dissolving Microneedles-Based Composite System for Eliciting Antitumor Immunity and the Abscopal Effect
复制标题
一种简便的低剂量光敏剂溶解微针复合系统，用于激发抗肿瘤免疫和远隔效应
DOI：
10.1021/acsnano.1c06225
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发表时间：
2021-12-28
期刊：
影响因子：
17.1
通讯作者：
Gao, Jianqing
中科院分区：
文献类型：
--
作者：
Bian, Qiong;Huang, Lingling;Gao, Jianqing
基于纳米医学的光动力学疗法（PDT）治疗黑色素瘤引起了人们的极大关注。然而，聚合物纳米颗粒的复杂设计和静脉注射中使用的高剂量光敏剂（用于肿瘤病灶中药物的充分积累）对商业化和进一步的临床应用提出了巨大的挑战。在此，我们通过简单的制造方法制造了二氢卟酚e6（L-Ce 6 NAs）集成的快速溶解微针贴片（L-Ce 6 MN）的无载体纳米组装体，所述微针贴片在针尖中仅富集约3 μ g的Ce 6。L-Ce 6 MN具有足够的机械强度以穿透皮肤，并促进L-Ce 6 NA运输至皮肤下200-500 μ m的深度，从而实现有效和准确的药物递送至肿瘤病变。在异种移植小鼠黑色素瘤模型中，具有低剂量Ce 6（0.12 mg/kg）的基于L-Ce 6 MN的PDT通过活性氧（ROS）的产生而在原位发挥原发性病变的有效消融。更重要的是，还通过激活免疫原性细胞死亡（ICD）和释放免疫原性相关分子模式（DAMP）引起显著的远位效应，这反过来又促进树突状细胞（DC）成熟和随后的抗原呈递，从而促进T细胞介导的免疫应答而无需协同免疫疗法。总的来说，我们的研究结果表明，具有低剂量光敏剂的易操作、可控和快速溶解的微针贴片为增强的光免疫疗法提供了巨大的治疗潜力。
Nanomedicine-based photodynamic therapy (PDT) for melanoma treatment has attracted great attention. However, the complex design of polymer nanoparticles and high doses of photosensitizers used in intravenous injections (for sufficient accumulation of drugs in tumor lesions) pose a huge challenge to the commercialization and further clinical application. Herein, we fabricated the carrier-free nanoassemblies of a chlorin e6 (L-Ce6 NAs)-integrated fast-dissolving microneedles patch (L-Ce6 MNs) enriching only about 3 mu g of Ce6 in the needle tips via a facile fabrication method. The L-Ce6 MNs had sufficient mechanical strength to penetrate the skin and facilitated the transportation of L-Ce6 NAs to a depth of 200-500 mu m under the skin, thereby achieving efficient and accurate drug delivery to tumor lesions. In a xenograft mouse melanoma model, the L-Ce6 MNs-based PDT with low dose of Ce6 (0.12 mg/kg) exerted efficient ablation of the primary lesions in situ through reactive oxygen species (ROS) generation. More importantly, a significant abscopal effect was also elicited by activating immunogenic cell death (ICD) and releasing danger-associated molecular patterns (DAMPs), which in turn promoted dendritic cells (DCs) maturation and the subsequent antigen presentation, thereby facilitating the T-cell-mediated immune response without synergetic immunotherapies. Collectively, our findings indicate the facile, controllable, and fast-dissolving microneedles patch with a low dose of photosensitizers presented great therapeutic potential for enhanced photoimmunotherapy.