Combined Delivery of Temozolomide and Anti-miR221 PNA Using Mesoporous Silica Nanoparticles Induces Apoptosis in Resistant Glioma Cells

Bertucci, Alessandro; Prasetyanto, Eko Adi; Septiadi, Dedy; Manicardi, Alex; Brognara, Eleonora; Gambari, Roberto; Corradini, Roberto; Cola, Luisa De

doi:10.1002/smll.201500540

Cited by 130 publications

(80 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The high EE and DLC achieved in the present study, as compared to the previous reports 13, 26, 27 was probably due to the partitioning of TMZ in the hydrophobic patches of Lf in the LfNPs.…”

Section: Resultscontrasting

confidence: 50%

Overcoming blood brain barrier with a dual purpose Temozolomide loaded Lactoferrin nanoparticles for combating glioma (SERP-17-12433)

Kumari

Ahsan

Kumar

et al. 2017

Sci Rep

122

View full text Add to dashboard Cite

Targeted delivery of drugs to the brain is challenging due to the restricted permeability across the blood brain barrier (BBB). Gliomas are devastating cancers and their positive treatment outcome using Temozolomide (TMZ) is limited due to its short plasma half-life, systemic toxicity and limited access through the blood-brain barrier (BBB). Nanoparticles made of Lactoferrin (Lf) protein, have been shown to enhance the pharmacological properties of drugs. Here, we report the specific ability of Lf nanoparticles to cross BBB and target over-expressed Lf receptors on glioma for enhanced TMZ delivery. TMZ-loaded Lf nanoparticles (TMZ-LfNPs) were prepared by our previously reported sol-oil method. While the Lf protein in the NP matrix aids in transcytosis across the BBB and preferential tumor cell uptake, the pH responsiveness leads to TMZ release exclusively in the tumor microenvironment. Delivery through LfNPs results in an enhanced and sustained intracellular concentration of TMZ in GL261 cells in vitro along with improving its in vivo pharmacokinetics and brain accumulation. TMZ-LfNPs treatment results in a significant reduction of tumor volume, higher tumor cell apoptosis and improved median survival in glioma bearing mice. These results demonstrate that LfNPs present an efficient TMZ delivery platform for an effective treatment of gliomas.

show abstract

Section: Resultscontrasting

confidence: 50%

Overcoming blood brain barrier with a dual purpose Temozolomide loaded Lactoferrin nanoparticles for combating glioma (SERP-17-12433)

Kumari

Ahsan

Kumar

et al. 2017

Sci Rep

122

View full text Add to dashboard Cite

show abstract

“…Increasing number of studies have reported that miRNAs can enhance the sensitivity of glioma cells to TMZ or improve TMZ-induced apoptosis of miR-181b [30], and miR-143 [31]. Furthermore, antisense miRNA has been used as an adjuvant agent for evaluating the effects of TMZ on glioma cells [32, 33]. Taken together, elucidation of TMZ-mediated miRNA networks can provide novel directions for understanding TMZ-mediated cytotoxic mechanisms.…”

Section: Discussionmentioning

confidence: 99%

The Inhibition of microRNA-128 on IGF-1-Activating mTOR Signaling Involves in Temozolomide-Induced Glioma Cell Apoptotic Death

et al. 2016

View full text Add to dashboard Cite

Temozolomide (TMZ), an alkylating agent of the imidazotetrazine series, is a first-line chemotherapeutic drug used in the clinical therapy of glioblastoma multiforme, the most common and high-grade primary glioma in adults. Micro (mi)RNAs, which are small noncoding RNAs, post-transcriptionally regulate gene expressions and are involved in gliomagenesis. However, no studies have reported relationships between TMZ and miRNA gene regulation. We investigated TMZ-mediated miRNA profiles and its molecular mechanisms underlying the induction of glioma cell death. By performing miRNA microarray and bioinformatics analyses, we observed that expression of 248 miRNAs was altered, including five significantly upregulated and 17 significantly downregulated miRNAs, in TMZ-treated U87MG cells. miR-128 expression levels were lower in different glioma cells and strongly associated with poor survival. TMZ treatment significantly upregulated miR-128 expression. TMZ significantly enhanced miR-128-1 promoter activity and transcriptionally regulated miR-128 levels through c-Jun N-terminal kinase 2/c-Jun pathways. The overexpression and knockdown of miR-128 expression significantly affected TMZ-mediated cell viability and apoptosis-related protein expression. Furthermore, the overexpression of miR-128 alone enhanced apoptotic death of glioma cells through caspase-3/9 activation, poly(ADP ribose) polymerase degradation, reactive oxygen species generation, mitochondrial membrane potential loss, and non-protective autophagy formation. Finally, we identified that key members in mammalian target of rapamycin (mTOR) signaling including mTOR, rapamycin-insensitive companion of mTOR, insulin-like growth factor 1, and PIK3R1, but not PDK1, were direct target genes of miR-128. TMZ inhibited mTOR signaling through miR-128 regulation. These results indicate that miR-128-inhibited mTOR signaling is involved in TMZ-mediated cytotoxicity. Our findings may provide a better understanding of cytotoxic mechanisms of TMZ involved in glioblastoma development.

show abstract

“…Mesoporous silica NPs containing polyarginine-peptide nucleic acid (R8-PNA) conjugates targeting miR221 were used to treat temozolomide (TMZ)-resistant glioma cells. These NPs, combined with TMZ treatment, led to a significant increase in apoptosis [51]. …”

Section: Using Nanotechnology Formulations To Deliver Mirnas To Tumorsmentioning

confidence: 99%

miRNA nanotherapeutics for cancer

Ganju

Khan

Hafeez

et al. 2017

Drug Discovery Today

257

165

View full text Add to dashboard Cite

miRNAs are noncoding RNA molecules that regulate gene expression through diverse mechanisms. Increasing evidence suggests that miRNA-based therapies, either restoring or repressing miRNA expression and activity, hold great promise. However, the efficient delivery of miRNAs to target tissues is a major challenge in the transition of miRNA therapy to the clinic. Cationic polymers or viral vectors are efficient delivery agents but their systemic toxicity and immunogenicity limit their clinical usage. Efficient targeting and sustained release of miRNAs/anti-miRNAs using nanoparticles (NPs) conjugated with antibodies and/or peptides could reduce the required therapeutic dosage while minimizing systemic and cellular toxicity. Given their importance in clinical oncology, here we focus on the development of miRNA nanoformulations to achieve enhanced cellular uptake, bioavailability, and accumulation at the tumor site.

show abstract

Combined Delivery of Temozolomide and Anti-miR221 PNA Using Mesoporous Silica Nanoparticles Induces Apoptosis in Resistant Glioma Cells

Cited by 130 publications

References 83 publications

Overcoming blood brain barrier with a dual purpose Temozolomide loaded Lactoferrin nanoparticles for combating glioma (SERP-17-12433)

Overcoming blood brain barrier with a dual purpose Temozolomide loaded Lactoferrin nanoparticles for combating glioma (SERP-17-12433)

The Inhibition of microRNA-128 on IGF-1-Activating mTOR Signaling Involves in Temozolomide-Induced Glioma Cell Apoptotic Death

miRNA nanotherapeutics for cancer

Contact Info

Product

Resources

About