Multifunctional Nanoparticle Loaded Injectable Thermoresponsive Hydrogel as NIR Controlled Release Platform for Local Photothermal Immunotherapy to Prevent Breast Cancer Postoperative Recurrence and Metastases
Multifunctional Nanoparticle Loaded Injectable Thermoresponsive Hydrogel as NIR Controlled Release Platform for Local Photothermal Immunotherapy to Prevent Breast Cancer Postoperative Recurrence and Metastases
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装载多功能纳米颗粒的可注射热响应水凝胶作为近红外控释平台，用于局部光热免疫治疗，以预防乳腺癌术后复发和转移
DOI：
10.1002/adfm.202001059
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发表时间：
2020-05-11
影响因子：
19
通讯作者：
Wei, Xia Wei
中科院分区：
文献类型：
--
作者：
Jia, Yan Peng;Shi, Kun;Wei, Xia Wei
对于接受保乳手术的乳腺癌患者来说，有效的治疗以防止局部复发和转移是非常必要的。在这里，开发了一种基于具有近红外（NIR）刺激药物释放的热敏PLEL水凝胶的局部可注射治疗平台，以实现用于预防乳腺癌术后复发的协同光热免疫治疗。自组装多功能纳米颗粒（RIC NP）由三种治疗组分组成，包括光热剂吲哚菁绿色、TLR-7/8激动剂瑞喹莫特（R848）和TLR-9激动剂CPG ODN。将RIC NP物理掺入热敏PLEL水凝胶中。然后将RIC NPs包封的PLEL水凝胶（RIC NPs@PLEL）局部注射到肿瘤切除腔中用于局部光热治疗以消融残余肿瘤组织并产生肿瘤相关抗原。同时，NIR还触发免疫组分CPG ODN和R848从温敏水凝胶PLEL中释放。释放的免疫组分与肿瘤相关抗原一起，通过诱导有效和持续的抗肿瘤免疫效应，作为用于手术后免疫治疗的原位癌症疫苗。总体而言，这项工作表明，光热免疫治疗的基础上，局部水凝胶输送系统具有很大的潜力，作为一个有前途的工具，乳腺癌的术后管理，以防止复发和转移。
For breast cancer patients who have undergone breast-conserving surgery, effective treatments to prevent local recurrences and metastases is very essential. Here, a local injectable therapeutic platform based on a thermosensitive PLEL hydrogel with near-infrared (NIR)-stimulated drug release is developed to achieve synergistic photothermal immunotherapy for prevention of breast cancer postoperative relapse. Self-assembled multifunctional nanoparticles (RIC NPs) are composed of three therapeutic components including indocyanine green, a photothermal agent; resiquimod (R848), a TLR-7/8 agonist; and CPG ODNs, a TLR-9 agonist. RIC NPs are physically incorporated into the thermosensitive PLEL hydrogel. The RIC NPs encapsulated PLEL hydrogel (RIC NPs@PLEL) is then locally injected into the tumor resection cavity for local photothermal therapy to ablate residue tumor tissues and produce tumor-associated antigens. At the same time, NIR also triggers the release of immune components CPG ODNs and R848 from thermoresponsive hydrogels PLEL. The released immune components, together with tumor-associated antigens, work as an in situ cancer vaccine for postsurgical immunotherapy by inducing effective and sustained antitumor immune effect. Overall, this work suggests that photothermal immunotherapy based on local hydrogel delivery system has great potential as a promising tool for the postsurgical management of breast cancer to prevent recurrences and metastases.