Tissue-Penetrating Delivery of Compounds and Nanoparticles into Tumors

Sugahara, Kazuki N.; Teesalu, Tambet; Karmali, Priya; Kotamraju, Venkata Ramana; Agemy, Lilach; Girard, Olivier; Hanahan, Douglas; Mattrey, Robert F.; Ruoslahti, Erkki

doi:10.1016/j.ccr.2009.10.013

Cited by 1,007 publications

(1,213 citation statements)

References 49 publications

Supporting

Mentioning

1,186

Contrasting

Unclassified

Order By: Relevance

“…We then seeded the chamber with ∼10 4 PPC-1 human prostate carcinoma cells in 2 mL of culture medium. PPC-1 cells were selected as a model because they express high levels of NRP-1, a well characterized receptor that binds and internalizes peptides with C-terminal arginine residues, typically within a consensus context of R/KXXR/K (the C-end Rule or CendR motif) (29)(30)(31). As a negative control, we used phage expressing hepta-glycine (G7), which exhibits negligible binding to PPC-1 cells (28).…”

Section: Resultsmentioning

confidence: 99%

Selection of phage-displayed peptides on live adherent cells in microfluidic channels

Wang

Teesalu

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Affinity reagents that bind to specific molecular targets are an essential tool for both diagnostics and targeted therapeutics. There is a particular need for advanced technologies for the generation of reagents that specifically target cell-surface markers, because transmembrane proteins are notoriously difficult to express in recombinant form. We have previously shown that microfluidics offers many advantages for generating affinity reagents against purified protein targets, and we have now significantly extended this approach to achieve successful in vitro selection of T7 phagedisplayed peptides that recognize markers expressed on live, adherent cells within a microfluidic channel. As a model, we have targeted neuropilin-1 (NRP-1), a membrane-bound receptor expressed at the surface of human prostate carcinoma cells that plays central roles in angiogenesis, cell migration, and invasion. We show that, compared to conventional biopanning methods, microfluidic selection enables more efficient discovery of peptides with higher affinity and specificity by providing controllable and reproducible means for applying stringent selection conditions against minimal amounts of target cells without loss. Using our microfluidic system, we isolate peptide sequences with superior binding affinity and specificity relative to the well known NRP-1-binding RPARPAR peptide. As such microfluidic systems can be used with a wide range of biocombinatorial libraries and tissue types, we believe that our method represents an effective approach toward efficient biomarker discovery from patient samples.

show abstract

Section: Resultsmentioning

confidence: 99%

Selection of phage-displayed peptides on live adherent cells in microfluidic channels

Wang

Teesalu

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Through phage display35 and in vivo biopanning techniques, lots of core ligand fragments or homing peptides targeting specific organs or tissues have been obtained and verified, so that targeting modification of exosomes can be realized. Displaying the tumor penetration peptide iRGD (CRGDKGPDC)36 on the surface of exosomes enabled them to specifically deliver doxorubicin to breast cancer cells expressing αv integrins, leading to inhibition of tumor growth 37. GE11 peptide (YHWYGYTPQNVI) fused to exosomes facilitates exosomes loaded with therapeutic microRNA targeting epidermal growth factor receptor–positive xenograft breast cancer cells 38.…”

Section: Discussionmentioning

confidence: 99%

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Wang

Chen

Zhao

et al. 2018

JAHA

286

206

View full text Add to dashboard Cite

BackgroundExosomes are membranous vesicles generated by almost all cells. Recent studies demonstrated that mesenchymal stem cell–derived exosomes possessed many effects, including antiapoptosis, anti‐inflammatory effects, stimulation of angiogenesis, anticardiac remodeling, and recovery of cardiac function on cardiovascular diseases. However, targeting of exosomes to recipient cells precisely in vivo still remains a problem. Ligand fragments or homing peptides discovered by phage display and in vivo biopanning methods fused to the enriched molecules on the external part of exosomes have been exploited to improve the ability of exosomes to target specific tissues or organs carrying cognate receptors. Herein, we briefly elucidated how to improve targeting ability of exosomes to ischemic myocardium.Methods and ResultsWe used technology of molecular cloning and lentivirus packaging to engineer exosomal enriched membrane protein (Lamp2b) fused with ischemic myocardium‐targeting peptide CSTSMLKAC (IMTP). In vitro results showed that IMTP‐exosomes could be internalized by hypoxia‐injured H9C2 cells more efficiently than blank‐exosomes. Compared with blank‐exosomes, IMTP‐exosomes were observed to be increasingly accumulated in ischemic heart area (P<0.05). Meanwhile, attenuated inflammation and apoptosis, reduced fibrosis, enhanced vasculogenesis, and cardiac function were detected by mesenchymal stem cell–derived IMTP‐exosome treatment in ischemic heart area.ConclusionsOur research concludes that exosomes engineered by IMTP can specially target ischemic myocardium, and mesenchymal stem cell–derived IMTP‐exosomes exert enhanced therapeutic effects on acute myocardial infarction.

show abstract

“…74 Critically, iRGD can increase the permeability of tumor cells, mediate cellular internalization and extravasation and enhance deep tissue penetration to improve the imaging sensitivity and therapeutic efficacy mediated by integrins and neuropilin-1 (NRP-1) receptors. 75 …”

Section: Applying Spion To the Imaging Of Pancreatic Duct Adenocarcinmentioning

confidence: 99%

Superparamagnetic iron oxide nanoparticles for MR imaging of pancreatic cancer: Potential for early diagnosis through targeted strategies

Zhang¹,

Zou²,

Chen³

et al. 2015

Asia-Pac J Clncl Oncology

View full text Add to dashboard Cite

Superparamagnetic iron oxide nanoparticles (SPION)-based magnetic resonance imaging is a powerful, noninvasive tool in biomedical imaging. The recent embedding of SPIO in nanoencapsulations that had different controllable surface properties has now made it possible to use SPIO in the imaging of metabolic processes. The two major issues to realize maximized and selective SPIO cancer targeting are the minimization of macrophage uptake and the preferential binding to cancerous cells over healthy neighbor cells. The utility of SPIO has been shown in clinical applications using a series of marketed SPION-based contrast agents. Applications have ranged from detecting inflammatory diseases to the specific identification of cell surface markers expressed on tumors. This review focuses on iron-oxide-based nanoparticles, to include the physiochemical properties of SPION surface engineering and its synthetic methods as well as SPIO imaging applications and specifically targeted SPIO conjugates (e.g. targeted probes) for labeling cancerous, cell-surface molecules. As a specific application of this technology, we discuss its use in the imaging of pancreatic duct adenocarcinoma in addition to its potential for use in early diagnosis through targeted strategies.

show abstract

Tissue-Penetrating Delivery of Compounds and Nanoparticles into Tumors

Cited by 1,007 publications

References 49 publications

Selection of phage-displayed peptides on live adherent cells in microfluidic channels

Selection of phage-displayed peptides on live adherent cells in microfluidic channels

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Superparamagnetic iron oxide nanoparticles for MR imaging of pancreatic cancer: Potential for early diagnosis through targeted strategies

Contact Info

Product

Resources

About