Nanoparticles with rough surface improve the therapeutic effect of photothermal immunotherapy against melanoma  

作　　者：Jiao Xue Yining Zhu Shuting Bai Chunting He Guangsheng Du Yuandong Zhang Yao Zhong Wenfei Chen Hairui Wang Xun Sun 

机构地区：[1]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province,Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology,West China School of Pharmacy,Sichuan University,Chengdu 610041,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第6期2934-2949,共16页药学学报（英文版）

基　　金：the financial support of the National Natural Science Foundation of China (Nos.81925036 & 81872814);the Science & Technology Major Project of Sichuan Province (No.2018SZDZX0018,China);the Key Research and Development Program of Science and Technology Department of Sichuan Province (No.2020YFS0570,China);111 project (No.b18035,China);the Fundamental Research Funds for the Central Universities (China)。

摘　　要：Photothermal therapy has been intensively investigated for treating cancer in recent years.However,the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence.To address this challenge,immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites.Here,we engineered silica-based core-shell nanoparticles(JQ-1@PSNs-R),in which silica cores were coated with the photothermal agent polydopamine,and a bromodomain-containing protein 4(BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photo thermal and immune therapy for tumor elimination.Importantly,to improve the therapeutic effect,we increased the surface roughness of the nanoparticles by hydrofluoric acid(HF) etching during the fabrication process,and found that the internalization of JQ-1@PSNs-R was significantly improved,leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1.In the animal studies,the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy,successfully activated tumor-specific immune responses against residual tumor cells,and further prevented tumor metastasis and recurrence.Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.

关 键 词：Photothermal therapy IMMUNOTHERAPY Rough surface Polydopamine-coated silica nanoparticles JQ-1 MELANOMA 

分 类 号：R739.5[医药卫生—肿瘤]