Cancer-targeted and intracellular delivery of Bcl-2-converting peptide with functional macroporous silica nanoparticles for biosafe treatment

Publication date: March 2020Source: Materials Science and Engineering: C, Volume 108Author(s): Yuehuang Wu, Pengjin Ge, Weixia Xu, Mingyu Li, Qi Kang, Xiaokun Zhang, Jingjing XieAbstractTherapeutic 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 μg/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 Bcl-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 apop...
Source: Materials Science and Engineering: C - Category: Materials Science Source Type: research