Therapeutic Nanocarriers Inhibit Chemotherapy-Induced Breast Cancer Metastasis.
Therapeutic Nanocarriers Inhibit Chemotherapy-Induced Breast Cancer Metastasis.
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DOI：
10.1002/advs.202203949
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发表时间：
2022-11
期刊：
影响因子：
15.1
通讯作者：
Leong, Kam W.
中科院分区：
文献类型：
--
作者：
Li, Tianyu;Akinade, Tolulope;Zhou, Jie;Wang, Hongxia;Tong, Qisong;He, Siyu;Rinebold, Emily;Salazar, Luis E. Valencia;Bhansali, Divya;Zhong, Yiling;Ruan, Jing;Du, Jinzhi;Dalerba, Piero;Leong, Kam W.
化疗虽然对原发性肿瘤有效，但可能通过引起受损细胞释放促炎因子而促进转移。在这里，开发了同时递送化疗剂和促炎因子以抑制化疗诱导的乳腺癌转移的聚合物纳米颗粒。阳离子纳米颗粒可以基于电荷-电荷相互作用吸附无细胞核酸（cfNA），其下调Toll样受体的表达，然后减少炎性细胞因子的分泌。通过体外结构优化，用药物结合十二烷基基团和二乙基乙醇胺表面基团（PAMAM-G3-C125-DEEA 20）修饰的阳离子聚酰胺胺（PAMAM）树枝状聚合物表现出最理想的纳米颗粒尺寸（约140 nm）、药物负载、细胞毒性、cfNA结合和抗炎活性的组合。在乳腺癌转移的小鼠模型中，与紫杉醇单独治疗相比，紫杉醇负载的纳米颗粒降低了cfNA和炎性细胞因子的血清水平，并抑制原发性肿瘤生长和肿瘤转移。此外，在血清或主要器官中未检测到显著的副作用。这些结果提供了一种将化疗药物递送至原发性肿瘤同时降低化疗的促转移作用的策略。开发了聚合物纳米颗粒，其同时递送化疗药物和肿瘤损伤相关分子模式以抑制化疗诱导的乳腺癌转移。阳离子纳米颗粒可以基于电荷-电荷相互作用吸附无细胞核酸，其下调Toll样受体的表达，从而减少炎性细胞因子的分泌。
Chemotherapy, although effective against primary tumors, may promote metastasis by causing the release of proinflammatory factors from damaged cells. Here, polymeric nanoparticles that deliver chemotherapeutics and scavenge proinflammatory factors simultaneously to inhibit chemotherapy‐induced breast cancer metastasis are developed. The cationic nanoparticles can adsorb cell‐free nucleic acids (cfNAs) based on charge–charge interaction, which downregulates the expression of Toll‐like receptors and then reduces the secretion of inflammatory cytokines. Through in vitro structural optimization, cationic polyamidoamine (PAMAM) dendrimers modified with drug‐binding dodecyl groups and diethylethanolamine surface groups (PAMAM‐G3‐C125‐DEEA20) exhibit the most desirable combination of nanoparticle size (≈140 nm), drug loading, cytotoxicity, cfNA binding, and anti‐inflammatory activity. In the mouse models of breast cancer metastasis, paclitaxel‐loaded nanoparticles reduce serum levels of cfNAs and inflammatory cytokines compared with paclitaxel treatment alone and inhibit both primary tumor growth and tumor metastasis. Additionally, no significant side effects are detected in the serum or major organs. These results provide a strategy to deliver chemotherapeutics to primary tumors while reducing the prometastatic effects of chemotherapy. Polymeric nanoparticles are developed, that deliver chemotherapeutics and scavenge damage‐associated molecular patterns simultaneously to inhibit chemotherapy‐induced breast cancer metastasis. The cationic nanoparticles can adsorb cell‐free nucleic acids based on charge–charge interaction, which downregulates the expression of Toll‐like receptors and then reduces the secretion of inflammatory cytokines.
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核酸清除超细纤维网抑制创伤引起的炎症和血栓形成。
影响因子：
14
作者：
Lee J;Jackman JG;Kwun J;Manook M;Moreno A;Elster EA;Kirk AD;Leong KW;Sullenger BA
通讯作者：
Sullenger BA
DOI：
10.1073/pnas.1105777108
发表时间：
2011-08-23
影响因子：
11.1
作者：
Lee, Jaewoo;Sohn, Jang Wook;Sullenger, Bruce A.
通讯作者：
Sullenger, Bruce A.
影响因子：
120.7
作者：
Bejnordi, Babak Ehteshami;Veta, Mitko;van der Laak, Jeroen A. W. M.
通讯作者：
van der Laak, Jeroen A. W. M.
特定的化疗药物通过基质和肿瘤来源的细胞因子和血管生成因子信号传导诱导转移行为。
影响因子：
7.3
作者：
Liu, Guanghua;Chen, Yang;Luo, Yongzhang
通讯作者：
Luo, Yongzhang
影响因子：
16.6
作者：
Bae, Y;Fukushima, S;Kataoka, K
通讯作者：
Kataoka, K