A novel pH- and glutathione-responsive drug delivery system based on in situ growth of MOF199 on mesoporous organic silica nanoparticles targeting the hepatocellular carcinoma niche
作者全名："Ling, Jiaji; Jiang, Yongmei; Yan, Shaoying; Dang, Hao; Yue, Huan; Liu, Kanglin; Kuang, Linghan; Liu, Xingxin; Tang, Hua"
作者地址："[Ling, Jiaji; Dang, Hao; Yue, Huan; Liu, Kanglin; Tang, Hua] Chongqing Med Univ, Affiliated Hosp 2, Key Lab Mol Biol Infect Dis, Dept Infect Dis,Inst Viral Hepatitis,Minist Educ, 1 Yi Xue Yuan Rd, Chongqing 400016, Peoples R China; [Ling, Jiaji; Jiang, Yongmei; Kuang, Linghan; Liu, Xingxin] Sichuan Univ, West China Univ Hosp 2, Dept Lab Med, Chengdu 610041, Sichuan, Peoples R China; [Yan, Shaoying] Nanchang Univ, Affiliated Hosp 1, Dept Clin Lab, Nanchang, Jiangxi, Peoples R China"
通信作者："Tang, H (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Key Lab Mol Biol Infect Dis, Dept Infect Dis,Inst Viral Hepatitis,Minist Educ, 1 Yi Xue Yuan Rd, Chongqing 400016, Peoples R China."
关键词：HCC therapy; Nanocarrier; pH-responsive; GSH-responsive; Multifunctional nanocomposites; Drug delivery
摘要："Background For people with advanced hepatocellular carcinoma (HCC), systemic chemotherapy remains the only choice of palliative treatment. However, chemotherapy efficacy is not effective due to its short blood circulation times, nonspecific cell and tissue biodistribution, and rapid metabolism or excretion from the body. Therefore, a targeted nanomedicine delivery system is urgently needed. Methods In order to improve the treatment efficiency of HCC, based on in situ growth of a copper metal organic framework on mesoporous organic silica nanoparticles, dual pH- and glutathione (GSH)-responsive multifunctional nanocomposites were synthesized as nanocarriers for enhanced HCC therapy. In this research, cellular uptake studies were performed using CLSM and Bio-TEM observations. Flow cytometry, AO-EB fluorescent staining, EdU test and Western blot were utilized to explore the apoptosis and proliferation process. In vivo imaging was employed to research the distribution of the nanocomposites in HCC tumor-bearing nude mice and the xenograft model of HCC tumor-bearing nude mice was applied to investigate the anti-tumor effects of drug-loaded nanocomposites in vivo. Results This newly constructed degradable nanocomposite DOX/SOR@SP94 and mPEG-anchored MONs@MOF199 (D/S@SPMM) has the benefits of controllable pore size, high encapsulation efficiency, and precise targeting. According to the results of in vivo imaging and anti-tumor studies, as well as pharmacokinetic research, D/S@SPMM possessed precise HCC tumor targeting and long-lasting accumulation properties at the tumor region. Compared with traditional chemotherapy and non-targeted drug delivery systems, anti-tumor efficiency was increased by approximately 10- and 5-fold, respectively. The nanocomposites exhibited excellent anti-tumor properties without inducing observable systemic toxicity, owing to efficient DOX and SOR loading and release as well as the HCC specific targeting peptide SP94. Conclusions The in vitro and in vivo anti-tumor results indicated that these nanocomposites could be an efficient nanomedicine for targeting HCC therapy."
基金机构："Key Laboratory of Infectious Diseases, CQMU ; Science and Technology Bureau of Chengdu [2021-YF05-01691-SN]; Province Natural Science Foundation of Sichuan Province [2022NSFSC1420]; West China Second University Hospital Clinical Research Fund [KL105]"
基金资助正文："This study was supported by the Key Laboratory of Infectious Diseases, CQMU (202004), the Grant from Science and Technology Bureau of Chengdu (No. 2021-YF05-01691-SN), the Province Natural Science Foundation of Sichuan Province (2022NSFSC1420), and the West China Second University Hospital Clinical Research Fund (No.KL105)."