The goal of the proposed research is to use mesoporous silica nanoparticles with bistable molecular machines to deliver anticancer drugs. The active structures are nanomachines that consist of a solid silica support that contains designed pores, and moving parts that trap drug molecules and release them from the pores only on external command or under desired conditions. Two types of machines, nanoimpellers that actively eject molecules from the pores, and nanovalves that block and unblock the entrances to the pores will be used to control the delivery of drugs. The assembly is coated with molecules or proteins that target the capsules to cancer cells. The first specific aim is to improve and optimize nanomachines (a pH activated valve, a light-activated impeller, a light activated valve) that were developed in the principal investigators laboratories, modify the surfaces for specific cancer cell targeting, and optimize their performance.
The second aim will demonstrate operation of the machines in human cancer cells by studying the release of a fluorescent DNA binding agent and to demonstrate the delivery and on-demand release of anticancer drugs (paclitaxel, camptothecin and doxorubicin) in human carcinoma cell lines. Finally, the third aim will evaluate and utilize the nanoparticles in human tumor xenografts grown in athymic mice. By having the valves open only in a tumor, it will be possible to achieve release of anticancer drugs only at specific sites or in response to specific stimuli, thus eliminating unwanted effects on non-cancerous cells. The nano valves and impellers allow sophisticated control of the delivery of the drugs.

Public Health Relevance

Nanoparticles that contain pores controlled by molecular machines will be used to release anticancer drugs under control. The result of the research will be a novel system for cancer chemotherapy that eliminates unwanted effects on non-cancerous cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA133697-04S1
Application #
8605676
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Ogunbiyi, Peter
Project Start
2010-01-01
Project End
2014-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
4
Fiscal Year
2013
Total Cost
$64,637
Indirect Cost
$22,665
Name
University of California Los Angeles
Department
Type
Organized Research Units
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Shahin, Sophia A; Wang, Ruining; Simargi, Shirleen I et al. (2018) Hyaluronic acid conjugated nanoparticle delivery of siRNA against TWIST reduces tumor burden and enhances sensitivity to cisplatin in ovarian cancer. Nanomedicine 14:1381-1394
Dong, Juyao; Zink, Jeffrey I (2016) Simultaneous spectroscopic measurements of the interior temperature and induced cargo release from pore-restricted mesoporous silica nanoparticles. Nanoscale 8:10558-63
Rühle, Bastian; Saint-Cricq, Philippe; Zink, Jeffrey I (2016) Externally Controlled Nanomachines on Mesoporous Silica Nanoparticles for Biomedical Applications. Chemphyschem 17:1769-79
Wu, Yilei; Shi, Rufei; Wu, Yi-Lin et al. (2015) Complexation of polyoxometalates with cyclodextrins. J Am Chem Soc 137:4111-8
Meng, Huan; Wang, Meiying; Liu, Huiyu et al. (2015) Use of a lipid-coated mesoporous silica nanoparticle platform for synergistic gemcitabine and paclitaxel delivery to human pancreatic cancer in mice. ACS Nano 9:3540-57
Yilmaz, M Deniz; Xue, Min; Ambrogio, Michael W et al. (2015) Sugar and pH dual-responsive mesoporous silica nanocontainers based on competitive binding mechanisms. Nanoscale 7:1067-72
Mekaru, Harutaka; Lu, Jie; Tamanoi, Fuyuhiko (2015) Development of mesoporous silica-based nanoparticles with controlled release capability for cancer therapy. Adv Drug Deliv Rev 95:40-9
Finlay, James; Roberts, Cai M; Dong, Juyao et al. (2015) Mesoporous silica nanoparticle delivery of chemically modified siRNA against TWIST1 leads to reduced tumor burden. Nanomedicine 11:1657-66
Hwang, Angela A; Lu, Jie; Tamanoi, Fuyuhiko et al. (2015) Functional nanovalves on protein-coated nanoparticles for in vitro and in vivo controlled drug delivery. Small 11:319-328
Saint-Cricq, P; Deshayes, S; Zink, J I et al. (2015) Magnetic field activated drug delivery using thermodegradable azo-functionalised PEG-coated core-shell mesoporous silica nanoparticles. Nanoscale 7:13168-13172

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