TY - JOUR
T1 - Silica nano supra-assembly for the targeted delivery of therapeutic cargo to overcome chemoresistance in cancer
AU - Thorat, Nanasaheb D.
AU - Bauer, Joanna
AU - Tofail, Syed A.M.
AU - Gascón Pérez, Victoria
AU - Bohara, Raghvendra A.
AU - Yadav, Hemraj M.
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Cancer cells become resistant over the period to chemotherapeutic drugs and pose a challenging impediment for oncologists in providing effective treatment. Nanomedicine allows to overcome chemoresistance and is the focus of our investigation. Silica nanostructures have been highlighted as an interesting drug delivery platform in vitro and in vivo applications. Here we show the validity of nanomedicine approach for targeted chemotherapeutic cargo delivery to overcome chemoresistance in cancer cells both in vitro and in vivo. For demonstrating the concept, we functionalised ∼100 nm long porous silica nanoparticles (∼20 nm diameter ordered pore structure) by conjugating anticancer drug, cytochrome c enzyme and dual-function anticancer aptamer AS1411 in single supra-assembled nanocargos. The supra-assembly on the porous silica nanostructure allows for a high loading of catalytic enzyme cytochrome c, anticancer drug and aptamer. The silica supra-assembly is characterized by transmission electron microscopy (TEM) and Brunauer-Emmett-Teller (BET) surface area analysis. Conjugation of cargoes has been monitored at each step by UV–vis and Fluorescence spectroscopy. Finally, the constructed supra-assembled nanocarrier tested on chemoresistance colon cancer (HCT116) cells. A pH-responsive, intracellular theranostic cargo delivery has been achieved and the triple action of the nanocargo made an efficient killing of drug resistance colon cancer cells in vitro (∼ 92% cell death) through triplex therapy effects by supressing the P-glycoprotein (P-gp) level. Furthermore, in vivo animal toxicity studies demonstrated, the supra-assembled nanocargos have encouraging safety index to be used in cancer therapy and drug delivery applications.
AB - Cancer cells become resistant over the period to chemotherapeutic drugs and pose a challenging impediment for oncologists in providing effective treatment. Nanomedicine allows to overcome chemoresistance and is the focus of our investigation. Silica nanostructures have been highlighted as an interesting drug delivery platform in vitro and in vivo applications. Here we show the validity of nanomedicine approach for targeted chemotherapeutic cargo delivery to overcome chemoresistance in cancer cells both in vitro and in vivo. For demonstrating the concept, we functionalised ∼100 nm long porous silica nanoparticles (∼20 nm diameter ordered pore structure) by conjugating anticancer drug, cytochrome c enzyme and dual-function anticancer aptamer AS1411 in single supra-assembled nanocargos. The supra-assembly on the porous silica nanostructure allows for a high loading of catalytic enzyme cytochrome c, anticancer drug and aptamer. The silica supra-assembly is characterized by transmission electron microscopy (TEM) and Brunauer-Emmett-Teller (BET) surface area analysis. Conjugation of cargoes has been monitored at each step by UV–vis and Fluorescence spectroscopy. Finally, the constructed supra-assembled nanocarrier tested on chemoresistance colon cancer (HCT116) cells. A pH-responsive, intracellular theranostic cargo delivery has been achieved and the triple action of the nanocargo made an efficient killing of drug resistance colon cancer cells in vitro (∼ 92% cell death) through triplex therapy effects by supressing the P-glycoprotein (P-gp) level. Furthermore, in vivo animal toxicity studies demonstrated, the supra-assembled nanocargos have encouraging safety index to be used in cancer therapy and drug delivery applications.
KW - Anticancer
KW - Drug delivery
KW - Nanocargos
KW - Nanomedicine
KW - Silica
UR - http://www.scopus.com/inward/record.url?scp=85074213010&partnerID=8YFLogxK
U2 - 10.1016/j.colsurfb.2019.110571
DO - 10.1016/j.colsurfb.2019.110571
M3 - Article
C2 - 31683204
AN - SCOPUS:85074213010
SN - 0927-7765
VL - 185
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
M1 - 110571
ER -