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首页> 外文期刊>Materials science & engineering >Cancer-targeted and intracellular delivery of Bcl-2-converting peptide with functional macroporous silica nanoparticles for biosafe treatment
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Cancer-targeted and intracellular delivery of Bcl-2-converting peptide with functional macroporous silica nanoparticles for biosafe treatment

机译：具有功能性大孔二氧化硅纳米粒子的Bcl-2转化肽的靶向癌和细胞内递送，可进行生物安全治疗

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摘要

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.
机译：已证明治疗性肽NuBCP-9（N9）作为Bcl-2的功能转换器，在Bcl-2丰富的癌症中具有显着的抗癌功效。但是，它在临床使用中面临技术挑战，例如生物利用度低，生物稳定性容易破坏以及对细胞内部不敏感。鉴于中孔二氧化硅纳米颗粒（MSNs）有望成为治疗性大分子的运载工具，我们开发了一种具有叶酸（FA）表面涂层的癌细胞靶向性MSNs和具有N9肽的大孔负载能力的MSNs用于癌症治疗。我们的结果表明，功能性MSN在斑马鱼模型中具有比裸MSN更高的生物安全性，导致200μg / ml的死亡胚胎不到30％，这可能进一步针对过度表达叶酸受体（FR）的子宫颈可以通过FA竞争的方式替代HeLa细胞而不是FR阴性的正常胚胎肾HEK 293T细胞。具有功能性MSN传递的N9肽可以被HeLa细胞内在化，并以Bcl-2依赖性方式与线粒体共定位。此外，由FA修饰的MSN传递的N9肽具有出色的抗癌效率和很高的选择性，可诱导约52％的HeLa细胞凋亡。总而言之，我们的研究结果表明，具有大孔径的功能性MSN可以作为有效的纳米载体用于细胞内递送靶向药物的肽类药物，从而实现癌症治疗。

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