Journal
MATERIALS SCIENCE AND ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
Volume 108, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.msec.2019.110386
Keywords
Macroporous silica nanoparticles; Targeted delivery; Bcl-2-converting peptide; Cancer treatment; Folate receptor
Categories
Funding
- National Natural Science Foundation of China [81702988, U1405229, 81672749, 91429306, 81670709]
- Natural Science Foundation of Fujian Province [2017J05137, 2017J01145]
- Regional Demonstration of Marine Economy Innovative Development Project [16PYY007SF17]
- Fujian Provincial Science and Technology Department [2017YZ0002-1]
- XMU Training Program of Innovation and Enterpreneurship for Undergraduates [2018X0557, 2018Y0921]
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Therapeutic peptide, NuBCP-9 (N9) as a Bcl-2 functional converter, has been demonstrated to have the remarkable anticancer efficiency in Bcl-2-abundant cancer. However, it faced technical challenges in clinical use, such as the low bioavailability, the easily-destroyed bio-stability, and the insusceptibility to cellular interior. With the potential of mesoporous silica nanoparticles (MSNs) as the promising delivery vehicle of therapeutic macromolecules, we developed a kind of MSNs with the surface coating of folic acid (FA) for cancer cell targeting and with the macropore loading of N9 peptide for cancer therapy. Our results showed that the functional MSNs had the relatively greater biosafety than the naked MSNs in zebrafish models, leading to less than 30% embryo of death at 200 mu g/ml, which could further specifically target the folate receptor (FR)-overexpressed cervical cancer HeLa cells instead of FR-negative normal embryonic kidney HEK 293T cells in a FA-competitive manner. N9 peptide with the delivery of functional MSNs could be internalized by HeLa cells, and co-localized with mitochondria in a BcI-2-dependent manner. Moreover, N9 peptide delivered by FA-modified MSNs displayed the excellent anticancer efficiency with great selectivity, inducing approximately 52% HeLa cells into apoptosis. In summary, our results illustrated the potential of functional MSNs with large pore size as an efficient nanocarrier for the intracellular delivery of peptide drugs with targeting proteins to realize cancer therapy.
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