Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing Medical University, Chongqing, People's Republic of China.
Int J Nanomedicine. 2023 Jun 9;18:3109-3124. doi: 10.2147/IJN.S408855. eCollection 2023.
Breast cancer has become the most common cancer in women. Compare with other subtypes of breast cancer, triple-negative breast cancer (TNBC) is more likely to relapse and metastasize. Highly effective therapeutic strategies are desperately needed to be explored. In this study, a multifunctional nanoplatform is expected to mediate chemo-photothermal therapy, which can combine immunogenic cell death with checkpoint blockade to combat TNBC and distant metastasis.
Poly (lactic acid-glycolic acid)-Poly (ethylene glycol) (PLGA-PEG) nanoparticles (NPs), a type of polymeric NPs, loaded with IR780, a near-infrared (NIR) dye, and doxorubicin (DOX) as the chemotherapeutic drug, were assembled by an improved double emulsification method (designated as IDNPs). The characterization, intracellular uptake, biosafety, photoacoustic (PA) imaging performance, and biodistribution of IDNPs were studied. Chemo-photothermal therapeutic effect and immunogenic cell death (ICD) were evaluated both in vitro and in vivo. The potency of chemo-photothermal therapy-triggered ICD in combination with anti-PD-1 immune checkpoint blockade (ICB) immunotherapy in eliciting immune response and treating distant tumors was further investigated.
IR780 and DOX were successfully loaded into PLGA-PEG to form the IDNPs, with size of 243.87nm and Zeta potential of -6.25mV. The encapsulation efficiency of IR780 and DOX was 83.44% and 5.98%, respectively. IDNPs demonstrated remarkable on-site accumulation and PA imaging capability toward 4T1 TNBC models. Chemo-photothermal therapy demonstrated satisfactory therapeutic effects both in vitro and in vivo, and triggered ICD efficiently. ICD, in combination with anti-PD-1, provoked a systemic antitumor immune response against distant tumors.
Multifunctional IDNPs were successfully synthesized to mediate chemo-photothermal therapy, which combines immunogenic cell death with checkpoint blockade to combat TNBC and distant metastasis, showing great promise preclinically and clinically.
乳腺癌已成为女性最常见的癌症。与其他乳腺癌亚型相比，三阴性乳腺癌（TNBC）更容易复发和转移。迫切需要探索更有效的治疗策略。在这项研究中，期望一种多功能纳米平台能够介导化疗-光热治疗，将免疫原性细胞死亡与检查点阻断相结合，以治疗 TNBC 和远处转移。
聚（乳酸-乙醇酸）-聚（乙二醇）（PLGA-PEG）纳米粒子（NPs），一种聚合物 NPs，负载近红外（NIR）染料 IR780 和阿霉素（DOX）作为化疗药物，通过改进的双乳化法（命名为 IDNPs）组装而成。研究了 IDNPs 的表征、细胞内摄取、生物安全性、光声（PA）成像性能和体内分布。在体外和体内评估了化疗-光热治疗效果和免疫原性细胞死亡（ICD）。进一步研究了化疗-光热治疗触发的 ICD 与抗 PD-1 免疫检查点阻断（ICB）免疫治疗联合在引发免疫反应和治疗远处肿瘤方面的效果。
IR780 和 DOX 成功负载到 PLGA-PEG 中形成 IDNPs，粒径为 243.87nm，Zeta 电位为-6.25mV。IR780 和 DOX 的包封效率分别为 83.44%和 5.98%。IDNPs 对 4T1 TNBC 模型表现出显著的原位积累和 PA 成像能力。化疗-光热治疗在体外和体内均显示出令人满意的治疗效果，并有效地触发了 ICD。ICD 与抗 PD-1 联合使用，引发了针对远处肿瘤的全身性抗肿瘤免疫反应。
成功合成了多功能 IDNPs 来介导化疗-光热治疗，将免疫原性细胞死亡与检查点阻断相结合，以治疗 TNBC 和远处转移，在临床前和临床方面都显示出巨大的潜力。
