Vertaisarvioitu alkuperäisartikkeli tai data-artikkeli tieteellisessä aikakauslehdessä (A1)
A Multifunctional Porous Silicon Nanocarrier for Glioblastoma Treatment
Julkaisun tekijät: Luo Meihua, Li Yuchen, Peng Bo, White Jacinta, Mäkilä Ermei, Tong Wing Yin, Choi Chung Hang Jonathan, Day Bryan, Voelcker Nicolas H
Kustantaja: American Chemical Society
Julkaisuvuosi: 2023
Journal: Molecular Pharmaceutics
Tietokannassa oleva lehden nimi: MOLECULAR PHARMACEUTICS
Lehden akronyymi: MOL PHARMACEUT
Volyymi: 20
Julkaisunumero: 1
Aloitussivu: 545
Lopetussivun numero: 560
Sivujen määrä: 16
ISSN: 1543-8384
eISSN: 1543-8392
DOI: http://dx.doi.org/10.1021/acs.molpharmaceut.2c00763
Verkko-osoite: https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.2c00763
Clinical treatment of glioblastoma (GBM) remains a major challenge because of the blood-brain barrier, chemotherapeutic resistance, and aggressive tumor metastasis. The development of advanced nanoplatforms that can efficiently deliver drugs and gene therapies across the BBB to the brain tumors is urgently needed. The protein "downregulated in renal cell carcinoma" (DRR) is one of the key drivers of GBM invasion. Here, we engineered porous silicon nanoparticles (pSiNPs) with antisense oligonucleotide (AON) for DRR gene knockdown as a targeted gene and drug delivery platform for GBM treatment. These AON-modified pSiNPs (AON@pSiNPs) were selectively internalized by GBM and human cerebral microvascular endothelial cells (hCMEC/D3) cells expressing Class A scavenger receptors (SR-A). AON was released from AON@pSiNPs, knocked down DRR and inhibited GBM cell migration. Additionally, a penetration study in a microfluidic-based BBB model and a biodistribution study in a glioma mice model showed that AON@pSiNPs could specifically cross the BBB and enter the brain. We further demonstrated that AON@pSiNPs could carry a large payload of the chemotherapy drug temozolomide (TMZ, 1.3 mg of TMZ per mg of NPs) and induce a significant cytotoxicity in GBM cells. On the basis of these results, the nanocarrier and its multifunctional strategy provide a strong potential for clinical treatment of GBM and research for targeted drug and gene delivery.