Sancho-Albero Maria, Fenaroli Alessia Lucrezia, Scaccaglia Mirco, Matteo Cristina, Grasselli Chiara, Zucchetti Massimo, Frapolli Roberta, Nastasi Claudia, De Cola Luisa
Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan 20156, Italy.
Department of Oncology, Laboratory of Cancer Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan 20156, Italy.
ACS Omega. 2024 Sep 25;9(40):41225-41235. doi: 10.1021/acsomega.4c02838. eCollection 2024 Oct 8.
The combination of chemo- and immunotherapy was recently demonstrated to improve a patient's response to therapy, giving rise to an emerging cancer treatment known as chemoimmunotherapy (CIT). Despite the promising benefits of CIT, the most important challenges are (i) the simultaneous or time-controlled delivery of two drugs and (ii) the selective uptake into different cells for each of the drugs: cancer cells for the chemotherapeutic and macrophages for the immunostimulation actives. Herein, a delivery strategy based on morphologically different stimuli-responsive breakable organosilica nanocarriers is exploited to transport two distinct drugs in the different cells using different times of delivery. We employ stimulus-sensitive, PEGylated organosilica nanocages to encapsulate the chemotherapeutic agent doxorubicin, which is preferentially taken up by tumor cells vs macrophages. On the other hand, similar size mesoporous organosilica nanoparticles, preferentially internalized by macrophages, are filled with the immunostimulator resiquimod. The administration in a sequential manner of the two different nanocarriers allowed us to assess the integrated effect of the combined therapy versus treatment with a single drug. work clearly shows an important reduction of tumor cell viability when both chemo- and immunotherapeutic agents are delivered.
化疗与免疫疗法的联合使用最近被证明可改善患者的治疗反应，从而产生了一种新兴的癌症治疗方法，即化学免疫疗法（CIT）。尽管CIT有诸多益处，但最重要的挑战在于：（i）两种药物的同时或定时递送；（ii）每种药物对不同细胞的选择性摄取：化疗药物针对癌细胞，免疫刺激活性药物针对巨噬细胞。在此，我们利用基于形态不同的刺激响应性可断裂有机硅纳米载体的递送策略，在不同时间将两种不同药物递送至不同细胞。我们使用刺激敏感的聚乙二醇化有机硅纳米笼来包裹化疗药物阿霉素，肿瘤细胞比巨噬细胞更优先摄取该药物。另一方面，大小相似、优先被巨噬细胞内化的介孔有机硅纳米颗粒则填充有免疫刺激剂瑞喹莫德。以序贯方式给予两种不同的纳米载体，使我们能够评估联合治疗与单一药物治疗的综合效果。研究清楚地表明，当同时递送化疗和免疫治疗药物时，肿瘤细胞活力会显著降低。
