2020
DOI: 10.1126/sciadv.aaz9798
|View full text |Cite|
|
Sign up to set email alerts
|

Pretargeted delivery of PI3K/mTOR small-molecule inhibitor–loaded nanoparticles for treatment of non-Hodgkin’s lymphoma

Abstract: Overactivation of the PI3K/mTOR signaling has been identified in non-Hodgkin’s lymphoma. BEZ235 is an effective dual PI3K/mTOR inhibitor, but it was withdrawn from early-phase clinical trials owing to poor solubility and on-target/off-tumor toxicity. Here, we developed a nanoparticle (NP)–based pretargeted system for the therapeutic delivery of BEZ235 to CD20- and HLA-DR–expressing lymphoma cells for targeted therapy. The pretargeted system is composed of dibenzocyclooctyne-functionalized anti-CD20 and anti-Ly… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

0
22
0

Year Published

2020
2020
2024
2024

Publication Types

Select...
9
1

Relationship

2
8

Authors

Journals

citations
Cited by 38 publications
(22 citation statements)
references
References 36 publications
0
22
0
Order By: Relevance
“…DBCO-functionalized α-CD16, α-4-1BB, and α-EFGR were prepared via primary amine N -hydroxysuccinimide (NHS) coupling reaction with DBCO-NHCO-PEG13-NHS ester (BroadPharm; catalog number, BP-22960), as previously reported ( 26 , 46 ). The target degree of functionalization was 15 for α-CD16 and α-4-1BB, and 8 for α-EFGR.…”
Section: Methodsmentioning
confidence: 99%
“…DBCO-functionalized α-CD16, α-4-1BB, and α-EFGR were prepared via primary amine N -hydroxysuccinimide (NHS) coupling reaction with DBCO-NHCO-PEG13-NHS ester (BroadPharm; catalog number, BP-22960), as previously reported ( 26 , 46 ). The target degree of functionalization was 15 for α-CD16 and α-4-1BB, and 8 for α-EFGR.…”
Section: Methodsmentioning
confidence: 99%
“…Despite the promising efficacy in hematologic cancers, there is still a poor prognosis for solid tumors due to poor cancer-targeting specificity. A recent report indicates that a nanoparticle-based pre-targeted delivery system improves the therapeutic window of small-molecule inhibitors [161]. This approach increases the number of nanoparticles retained on the target tumor cells, improves the drug delivery, and shows the antitumor activity of BEZ235 through the inhibition of PI3K/mTOR.…”
Section: Discussionmentioning
confidence: 99%
“…For instance, proteoglycans and glycosaminoglycans biosynthesis related pathways have been reported to be involved in cancer development [ 25 , 26 ]. Another pathway regulated by miRNAs here described is the mTOR signaling, an intracellular member of the activator cascade within the BCR pathway, a well-known cascade responsible for cellular proliferation, survival, differentiation and migration of normal and malignant B cells [ 27 , 28 ]. In addition, pathways and processes associated to drug resistance were regulated as well by the miRNAs here found, such as the fatty acid biosynthesis and metabolism.…”
Section: Discussionmentioning
confidence: 99%