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A Multifunctional Porous Silicon Nanocarrier for Glioblastoma Treatment




Julkaisun tekijätLuo Meihua, Li Yuchen, Peng Bo, White Jacinta, Mäkilä Ermei, Tong Wing Yin, Choi Chung Hang Jonathan, Day Bryan, Voelcker Nicolas H

KustantajaAmerican Chemical Society

Julkaisuvuosi2023

JournalMolecular Pharmaceutics

Tietokannassa oleva lehden nimiMOLECULAR PHARMACEUTICS

Lehden akronyymiMOL PHARMACEUT

Volyymi20

Julkaisunumero1

Aloitussivu545

Lopetussivun numero560

Sivujen määrä16

ISSN1543-8384

eISSN1543-8392

DOIhttp://dx.doi.org/10.1021/acs.molpharmaceut.2c00763

Verkko-osoitehttps://pubs.acs.org/doi/10.1021/acs.molpharmaceut.2c00763


Tiivistelmä

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.


Last updated on 2023-23-02 at 14:23