TY - JOUR
T1 - Preoccupation of Empty Carriers Decreases Endo-/Lysosome Escape and Reduces the Protein Delivery Efficiency of Mesoporous Silica Nanoparticles
AU - Li, Wen Qing
AU - Sun, Li Ping
AU - Xia, Yiqiu
AU - Hao, Sijie
AU - Cheng, Gong
AU - Wang, Zhigang
AU - Wan, Yuan
AU - Zhu, Chuandong
AU - He, Hongzhang
AU - Zheng, Si Yang
N1 - Funding Information:
We appreciate the National Cancer Institute of the National Institutes of Health for funding this work (award no. DP2CA174508).
Funding Information:
*E-mail: sxz10@psu.edu. Phone: 1-(814) 865-8090. ORCID Gong Cheng: 0000-0002-2217-6408 Si-Yang Zheng: 0000-0002-0616-030X Author Contributions W.-Q.L. and L.-P.S. contributed equally. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Funding We appreciate the National Cancer Institute of the National Institutes of Health for funding this work (award no. DP2CA174508). Notes The authors declare no competing financial interest.
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/2/14
Y1 - 2018/2/14
N2 - Endo-/lysosome escape is a major challenge in nanoparticle-based protein delivery for cancer therapy. To enhance the endo-/lysosomal escape and increase the efficacy of protein delivery, current strategies mainly focus on destroying endo-/lysosomes by employing modified nanoparticles, such as pH-sensitive polyplexes, cell-penetrating peptides, and photosensitive molecules. Herein, we hypothesize that pretreatment with empty nanocarriers might make endo-/lysosomes occupied and affect the endo/lysosomal escape of protein subsequently delivery by nanocarriers. We first treated breast carcinoma MDA-MB-231 cells with a high concentration of empty nanocarriers, mesoporous silica nanoparticles (MSN), to occupy the endo-/lysosome. After 2 h, we treated the cells with a lower concentration of fluorescein isothiocyanate-labeled MSN (MSN-FITC) and investigated the intracellular spatial and temporal distribution of MSN-FITC and their colocalization with endo-/lysosomes. We discovered the preoccupation of endo-/lysosomes by the empty nanocarriers did exist, mainly through changing the spatial distribution of the subsequently introduced nanocarriers. Furthermore, for the protein delivery, we observed reduced MSN-saporin delivery after endo-/lysosome preoccupation by MSN empty carriers. A similar result is observed for the delivery of cytochrome C by MSN but not for the small-molecule anticancer drug doxorubicin. The results show that the empty nanocarriers inhibit the endo-/lysosome intracellular trafficking process and decrease the endo-/lysosome escape of proteins subsequently delivered by the nanocarriers. This new discovered phenomenon of declined endo-/lysosome escape after endo-/lysosome preoccupation indicates that repeated treatment by nanomaterials with low protein-loading capacity may not yield a good cancer therapeutic effect. Therefore, it provides a new insightful perspective on the role of nanomaterial carriers in intracellular protein delivery.
AB - Endo-/lysosome escape is a major challenge in nanoparticle-based protein delivery for cancer therapy. To enhance the endo-/lysosomal escape and increase the efficacy of protein delivery, current strategies mainly focus on destroying endo-/lysosomes by employing modified nanoparticles, such as pH-sensitive polyplexes, cell-penetrating peptides, and photosensitive molecules. Herein, we hypothesize that pretreatment with empty nanocarriers might make endo-/lysosomes occupied and affect the endo/lysosomal escape of protein subsequently delivery by nanocarriers. We first treated breast carcinoma MDA-MB-231 cells with a high concentration of empty nanocarriers, mesoporous silica nanoparticles (MSN), to occupy the endo-/lysosome. After 2 h, we treated the cells with a lower concentration of fluorescein isothiocyanate-labeled MSN (MSN-FITC) and investigated the intracellular spatial and temporal distribution of MSN-FITC and their colocalization with endo-/lysosomes. We discovered the preoccupation of endo-/lysosomes by the empty nanocarriers did exist, mainly through changing the spatial distribution of the subsequently introduced nanocarriers. Furthermore, for the protein delivery, we observed reduced MSN-saporin delivery after endo-/lysosome preoccupation by MSN empty carriers. A similar result is observed for the delivery of cytochrome C by MSN but not for the small-molecule anticancer drug doxorubicin. The results show that the empty nanocarriers inhibit the endo-/lysosome intracellular trafficking process and decrease the endo-/lysosome escape of proteins subsequently delivered by the nanocarriers. This new discovered phenomenon of declined endo-/lysosome escape after endo-/lysosome preoccupation indicates that repeated treatment by nanomaterials with low protein-loading capacity may not yield a good cancer therapeutic effect. Therefore, it provides a new insightful perspective on the role of nanomaterial carriers in intracellular protein delivery.
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U2 - 10.1021/acsami.7b18577
DO - 10.1021/acsami.7b18577
M3 - Article
C2 - 29345456
AN - SCOPUS:85042095511
SN - 1944-8244
VL - 10
SP - 5340
EP - 5347
JO - ACS applied materials & interfaces
JF - ACS applied materials & interfaces
IS - 6
ER -
