文献类型：期刊文献

英文题名：Antibacterial tellurium-containing polycarbonate drug carriers to eliminate intratumor bacteria for synergetic chemotherapy against colorectal cancer

作者：Hu, Jieni[1];Ran, Shujun[2];Huang, Zhengwei[2];Liu, Yanyuan[1];Hu, Haiyan[3];Zhou, Yan[3];Ding, Xiaomin[3];Yin, Junyi[3];Zhang, Yan[1]

机构：[1]East China Univ Sci & Technol, Sch Mat Sci & Engn, Shanghai Key Lab Adv Polymer Mat, Key Lab Ultrafine Mat,Minist Educ, Shanghai 200237, Peoples R China;[2]Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Endodont & Operat Dent, Sch Med,Coll Stomatol,Natl Ctr Stomatol,Natl Clin, Shanghai, Peoples R China;[3]Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, MD Clinicaltrial Ctr, 600 Yishan Rd, Shanghai 200233, Peoples R China

年份：2024

卷号：185

起止页码：323

外文期刊名：ACTA BIOMATERIALIA

收录：;EI(收录号：20243216812085);WOS:【SCI-EXPANDED(收录号:WOS:001309324400001)】；

基金：This work was supported by National Natural Science Foundation of China (51873062 , 52073093 , 82072967 , 82102866 , 82373391 , 81800953 , 82001033) , Science Foundation of Shanghai Sixth People's Hospital (NO. ynqn202114) , and the Research Discipline fund No. KQYJXK2020 from Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, and College of Stomatology, Shanghai Jiao Tong University.

语种：英文

外文关键词：Intratumor microbes; Fusobacterium nucleatum; Antibacteria; Tellurium; Polycarbonate

摘要：Intratumor microbes have attracted great attention in cancer research due to its influence on the tumorigenesis, progression and metastasis of cancer. However, the therapeutic strategies targeting intratumoral microbes are still in their infancy. Specific microorganisms, such as Fusobacterium nucleatum ( F. nucleatum ), are abundant in various cancer and always result in the CRC progression and chemotherapy resistance. Here, a combined anticancer and antibacterial therapeutic strategy is proposed to deliver antitumor drug to the tumors containing intratumor microbiota by the antibacerial polymeric drug carriers. We construct oral tellurium-containing drug carriers using a complex of tellurium-containing polycarbonate with cisplatin (PTE@CDDP). The results show that the particle size of the prepared nanoparticles could be maintained at about 105 nm in the digestive system environment, which is in line with the optimal particle size of oral nanomedicine. In vitro mechanism study indicates that the tellurium-containing polymers are highly effective in killing F.nucleatum through a membrane disruption mechanism. The pharmacokinetic experiments confirmed that PTE@CDDP has the potential function of enhancing the oral bioavailability of cisplatin. Both in vitro and in vivo studies show that PTE@CDDP could inhibit intratumor F.nucleatum and lead to a reduction in cell proliferation and inflammation in the tumor site. Together, the study identifies that the CDDP-loaded tellurium-containing nanoparticles have great potential for treating the F.nucleatum -promoted colorectal cancer (CRC) by combining intratumor microbiota modulation and chemotherapy. The synergistic therapeutic strategy provide new insight into treating various cancers combined with bacterial infection. The synthesized antibacterial polymer was first employed to remodel the intratumor microbes in tumor microenvironment (TME). Moreover, it was the first report of tellurium-containing polymers against F.nucleatum and employed for treatment of the CRC. A convenient oral dosage form of cisplatin (CDDP)loaded tellurium-containing nanoparticles (PTE@CDDP) was adopted here, and the synergistic antibacterial/chemotherapy effect occurred. The PTE@CDDP could quickly and completely eliminate F.nucleatum in a safe dose. In the CRC model, PTE@CDDP effectively reversed the inflammation level and even restored the intestinal barrier damaged by F.nucleatum . The ultrasensitive ROS-responsiveness of PTE@CDDP triggered the fast oxidation and efficient drug release of CDDP and thus a highly efficient apoptosis of the tumors. Therefore, the tellurium-containing polymers are expected to serve as novel antibacterial agentsin vivo and have great potential in the F.nucleatum-associated cancers. The achievements provided new insight into treating CRC and other cancers combined with bacterial infection. (c) 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.