Aboeleneen Sara B, Azevedo Grace M, Li Kejian, Wolverton Avery M, Scully Mackenzie A, Kramarenko George C, Day Emily S
Biomedical Engineering, University of Delaware, Newark, Delaware 19713, United States.
Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware 19716, United States.
ACS Appl Nano Mater. 2025 Aug 15;8(35):17311-17328. doi: 10.1021/acsanm.5c03543. eCollection 2025 Sep 5.
Triple-negative breast cancer (TNBC) is one of the most aggressive and challenging subtypes of breast cancer to treat, primarily due to a lack of targeted therapies. Photothermal therapy (PTT) has emerged as a promising noninvasive strategy, wherein systemically administered light-responsive nanoparticles accumulate at the tumor site and convert externally applied near-infrared light into heat, culminating in tumor ablation. Nonetheless, the clinical application of PTT is impeded by insufficient nanoparticle accumulation within tumors. We present the development of silica core/gold shell nanoshells that are coated with TNBC cell membranes (MWNS) to enhance tumor accumulation through homotypic recognition and immune evasion. We demonstrate that MWNS preferentially target 4T1 TNBC cells over EpH4-Ev noncancerous breast epithelial cells and accumulate more readily in orthotopic 4T1 TNBC tumors in mice following intravenous injection compared to poly-(ethylene glycol)-coated nanoshells (PEG-NS). Congruently, MWNS improved PTT and photoacoustic (PA) imaging of TNBC cells , relative to PEG-NS. When assessed in an orthotopic syngeneic spontaneous metastasis tumor model , intravenously administered MWNS notably enhanced PA signals throughout the tumor volume by ∼7X compared to PEG-NS. Moreover, MWNS-mediated PTT inhibited tumor growth by ∼1.7X, diminished intratumoral proliferation by 2X, increased intratumoral apoptosis by 1.8X, and curtailed the formation of lung metastases by 1.8X compared with PTT mediated by PEG-NS. These findings establish MWNS as a promising biomimetic platform for precision imaging and therapy of TNBC. With ongoing development, image-guided PTT mediated by MWNS could improve the prognosis for patients suffering from advanced TNBC or other solid tumor cancers that are refractory to existing therapies.
三阴性乳腺癌（TNBC）是最难治疗且最具挑战性的乳腺癌亚型之一，主要原因是缺乏靶向治疗方法。光热疗法（PTT）已成为一种有前景的非侵入性治疗策略，在此疗法中，经全身给药的光响应纳米颗粒会在肿瘤部位聚集，并将外部施加的近红外光转化为热量，最终实现肿瘤消融。尽管如此，纳米颗粒在肿瘤内的积累不足阻碍了PTT的临床应用。我们研发了一种二氧化硅核/金壳纳米壳，其表面包覆有TNBC细胞膜（MWNS），通过同源识别和免疫逃逸来增强肿瘤积累。我们证明，与EpH4-Ev非癌性乳腺上皮细胞相比，MWNS优先靶向4T1 TNBC细胞，并且与聚乙二醇包覆的纳米壳（PEG-NS）相比，静脉注射后MWNS在小鼠原位4T1 TNBC肿瘤中更容易积累。同样，相对于PEG-NS，MWNS改善了TNBC细胞的PTT和光声（PA）成像。在原位同基因自发转移肿瘤模型中进行评估时，与PEG-NS相比，静脉注射的MWNS使整个肿瘤体积内的PA信号显著增强了约7倍。此外，与PEG-NS介导的PTT相比，MWNS介导的PTT使肿瘤生长抑制了约1.7倍，肿瘤内增殖减少了2倍，肿瘤内凋亡增加了1.8倍，肺转移形成减少了1.8倍。这些发现确立了MWNS作为一种有前景的仿生平台，可用于TNBC的精准成像和治疗。随着研究的不断深入，MWNS介导的图像引导PTT可能会改善晚期TNBC或其他对现有疗法难治的实体肿瘤癌症患者的预后。
