Here we report that reactive oxygen species (ROS) can reprogram cancer cells to increase the expression of specific receptors and modulate the delivery of nanomaterials. Gold and γ-polyglutamic acid (γ-PGA) hybrid nanoparticles (PGANP) were prepared via a facile single-step process. Gold nanoclusters in PGANP were dispersed within the tangled γ-PGA matrix of the nanoparticles. The condensed assembly of gold nanoclusters in γ-PGA matrix enabled the interparticle plasmon coupling effect, which lacks in single gold nanoparticles. Compared with gold nanoparticles of the similar sizes, PGANP showed significantly higher absorbance at near infrared (NIR) wavelength and light-to-heat converting ratios, resulting in greater temperature increase upon NIR light irradiation. Pretreatment of HeLa cancer cells with methylene blue (MB) generated reactive oxygen species. The ROS reprogrammed the cancer cells to express higher cell membrane levels of gamma glutamyl transferase (GGT), which is known to bind to γ-PGA of PGANP. MB pretreatment significantly enhanced delivery of PGANP to cancer cells. Cancer cells internalized PGANP to a greater extent and, were highly susceptible to irradiation with NIR light, which reduced cell viability to near zero. In vivo, MB pretreatment of HeLa xenograft mice increased the expression of GGT in tumor tissues. In mice pretreated with MB and exposed to NIR irradiation, PGANP treatment resulted in complete tumor ablation. The strategy of actively reprogramming tumor membrane levels of target receptors could be widely applied to overcome the heterogeneity of cancer cells. Although we used interparticle plasmon coupling effect-based PGANP for proving the concept of receptor-modulated delivery, this strategy could be broadly applicable to the active modulation of the receptor-mediated delivery of anticancer nanomaterials.

在这里，我们报道活性氧（ROS）可以重新编程癌细胞以增加特定受体的表达并调节纳米材料的传递。金和γ-聚谷氨酸（γ-PGA）杂化纳米粒子（PGANP）是通过简便的单步过程制备的。PGANP中的金纳米簇分散在纳米颗粒纠缠的γ-PGA基质中。金纳米团簇在γ-PGA基质中的浓缩组装能够实现粒子间等离子体激元耦合效应，而单个金纳米粒子则缺乏。与类似尺寸的金纳米颗粒相比，PGANP在近红外（NIR）波长和光热转换比下显示出显着更高的吸光度，从而在NIR光照射下导致更大的温度升高。用亚甲蓝（MB）预处理HeLa癌细胞会产生活性氧。ROS对癌细胞进行了重新编程，使其表达更高的细胞膜水平的γ-谷氨酰转移酶（GGT），该酶已知与PGANP的γ-PGA结合。MB预处理显着增强了PGANP向癌细胞的递送。癌细胞在更大程度上内化了PGANP，并且高度易受NIR光照射，从而将细胞活力降低到接近零。在体内，MB预处理HeLa异种移植小鼠可增加肿瘤组织中GGT的表达。在用MB预处理并暴露于NIR辐射的小鼠中，PGANP治疗可导致肿瘤完全消融。主动重编程靶受体的肿瘤膜水平的策略可广泛应用于克服癌细胞的异质性。