期刊
ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 8, 期 10, 页码 4163-4174出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.1c00653
关键词
glioblastoma multiforme; tumor penetration; targeting peptide; drug delivery system; porous silicon nanoparticle
资金
- Basic Science Research Program through the National Research Foundation (NRF) of Korea - Ministry of Education [2018R1A6A1A03025124, 2018R1D1A1B07043383]
- Bio & Medical Technology Development Program of the NRF of Korea - Korean government (MSIT) [2019-M3A9H1103783]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI21C0239]
- National Research Foundation of Korea (NRF) - Korean Government (MSIP) [2018R1A5A2025964]
- National Research Foundation of Korea [2018R1D1A1B07043383] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
GBM is an aggressive malignant tumor that is difficult to regulate with conventional chemotherapy due to anatomical structure specificity, low drug targeting ability, and limited penetration depth. A study prepared four types of nanoparticles based on porous silicon nanoparticles incorporating PEG, iRGD peptide, and SIWV tetra-peptide, and evaluated their deep-tumor penetration abilities in different models. The SIWV tetra-peptide significantly enhanced the penetration depth of the nanoparticles and showed higher anticancer efficacy in therapeutic formulations, promising for nanotherapeutics and peptide-conjugated drugs for GBM.
Glioblastoma multiforme (GBM) is the most aggressive malignant tumor. It is difficult to regulate GBM using conventional chemotherapy-based methods due to its anatomical structure specificity, low drug targeting ability, and limited penetration depth capability to reach the tumor interior. Numerous approaches have been proposed to overcome such issues, including nanoparticle-based drug delivery system (DDS) with the development of GBM site targeting and penetration depth enhancing moieties (e.g., peptides, sugars, proteins, etc.). In this study, we prepared four different types of nanoparticles, which are based on porous silicon nanoparticles (pSiNPs) incorporating polyethylene glycol (PEG), iRGD peptide (well-known cancer targeting peptide), and SIWV tetra-peptide (a recently disclosed GBM-targeting peptide), and analyzed their deep-tumor penetration abilities in cell spheroids, in GBM patient-derived tumoroids, and in GBM xenograft mice. We found that SIWV tetra -peptide significantly enhanced the penetration depth of pSiNPs, and its therapeutic formulation (temozolomide-loaded/SIWV-functionalized pSiNPs) showed a higher anticancer efficacy compared with other formulations. These findings hold great promise for the development of nanotherapeutics and peptide-conjugated drugs for GBM.
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