title: Domino-Like Intercellular Delivery of Undecylenic Acid-Conjugated Porous Silicon Nanoparticles for Deep Tumor Penetration.
abstract: Improving the intratumoral distribution of anticancer agents remains the critical challenge for developing efficient cancer chemotherapy. Luminescent porous silicon nanoparticles (PSiNPs) have attracted considerable attention in the biomedical field especially in drug delivery. Here, we described the lysosomal exocytosis-mediated domino-like intercellular delivery of undecylenic acid-conjugated PSiNPs (UA-PSiNPs) for deep tumor penetration. UA-PSiNPs with significantly improved stability in physiological conditions were internalized into tumor cells by macropinocytosis-, caveolae-, and clathrin-mediated endocytosis and mainly colocalized with Golgi apparatus and lysosomes. Substantial evidence showed that UA-PSiNPs was excreted from cells via lysosomal exocytosis after cellular uptake. The exocytosed UA-PSiNPs induced a domino-like infection of adjacent cancer cells and allowed encapsulated doxorubicin (DOX) to deeply penetrate into both three-dimensional tumor spheroids and in vivo tumors. In addition, DOX-loaded UA-PSiNPs exhibited strong antitumor activity and few side effects in vivo. This study demonstrated that UA-PSiNPs as a drug carrier might be applied for deep tumor penetration, offering a new insight into the design of more efficient delivery systems of anticancer drugs.
authors.affiliation: National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan, Hubei 430074, China.
authors.forename: Tuying
authors.initials: T
authors.lastname: Yong
authors.affiliation: National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan, Hubei 430074, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan, Hubei 430074, China.
authors.forename: Xiaoqiong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan, Hubei 430074, China.
authors.forename: Fuying
authors.initials: F
authors.lastname: Li
authors.affiliation: National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan, Hubei 430074, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan, Hubei 430074, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan, Hubei 430074, China.
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
keywords: intercellular delivery; lysosomal exocytosis; porous silicon; tumor penetration; undecylenic acid conjugation