Your browser doesn't support javascript.
loading
A two-step precise targeting nanoplatform for tumor therapy via the alkyl radicals activated by the microenvironment of organelles.
Wang, Lei; Niu, Xiuxiu; Song, Qingling; Jia, Jiajia; Hao, Yongwei; Zheng, Cuixia; Ding, Kaili; Xiao, Huifang; Liu, Xinxin; Zhang, Zhenzhong; Zhang, Yun.
Afiliación
  • Wang L; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, 100 Kexu
  • Niu X; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, 100 Kexu
  • Song Q; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, 100 Kexu
  • Jia J; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, 100 Kexu
  • Hao Y; School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, 453003, China.
  • Zheng C; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, 100 Kexu
  • Ding K; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, 100 Kexu
  • Xiao H; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, 100 Kexu
  • Liu X; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, 100 Kexu
  • Zhang Z; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, 100 Kexu
  • Zhang Y; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, 100 Kexu
J Control Release ; 318: 197-209, 2020 02.
Article en En | MEDLINE | ID: mdl-31672622
With the in-depth research of organelles, the microenvironment characteristics of their own, such as the acid environment of lysosomes and the high temperature environment of mitochondria, could be used as a natural and powerful condition for tumor therapy. Based on this, we constructed a two-step precise targeting nanoplatform which can realize the drug release and drug action triggered by the microenvironment of lysosomes (endosomes) and mitochondria, respectively. To begin with, the mesoporous silica nanoparticles (MSNs) were modified with triphenylphosphonium (TPP) and loaded with 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH). Then, folic acid (FA) targeted pH-sensitive liposomes containing docetaxel (Lipo/DTX-FA) were prepared by thin-film dispersion method, and the core-shell AIPH/MSN-TPP@Lipo/DTX-FA nanoparticles were constructed by self-assembly during the hydration of the liposomes. When this nanoplatform entered into the tumor cells through FA receptor-mediated endocytosis, the pH-sensitive liposomes were destabilized in the lysosomes, resulting in the release of DTX and AIPH/MSN-TPP nanoparticles. After that, AIPH was delivered to mitochondria by AIPH/MSN-TPP, and the alkyl radicals produced by AIPH under the high temperature environment can cause oxidative damage to mitochondria. Not only that, the DTX could enhance the anti-tumor effect of AIPH by downregulating the expression of anti-apoptotic Bcl-2 protein. The in vitro and in vivo results demonstrate that this delivery system could induce apoptosis based on organelles' s own microenvironment, which provides a new approach for tumor therapy.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nanopartículas / Antineoplásicos Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nanopartículas / Antineoplásicos Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Países Bajos