Nanoparticle-induced vascular blockade in human prostate cancer

Agemy, Lilach; Sugahara, Kazuki N.; Kotamraju, Venkata Ramana; Gujraty, Kunal V.; Girard, Olivier; Kono, Yuko; Mattrey, Robert F.; Park, Ji Ho; Sailor, Michael J.; Jiménez, Ana I.; Cativiela, Carlos; Zanuy, David; Sayago, Francisco J.; Alemán, Carlos; Nussinov, Ruth; Ruoslahti, Erkki

doi:10.1182/blood-2010-03-274258

Cited by 154 publications

(197 citation statements)

References 30 publications

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“…elongated shape and which have been shown to have more effective targeting properties than spherical nanoparticles (23,24). The two peptides were synthesized as a chimeric peptide, which was covalently linked to the NWs through a 5K-polyethylene glycol (PEG) linker ( Fig.…”

Section: Cgkrk Peptide Homes To Brain Tumors and Colocalizes With Mito-mentioning

confidence: 99%

Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma

Agemy

Friedmann‐Morvinski

Kotamraju

et al. 2011

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

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323

309

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Antiangiogenic therapy can produce transient tumor regression in glioblastoma (GBM), but no prolongation in patient survival has been achieved. We have constructed a nanosystem targeted to tumor vasculature that incorporates three elements: ( i ) a tumor-homing peptide that specifically delivers its payload to the mitochondria of tumor endothelial cells and tumor cells, ( ii ) conjugation of this homing peptide with a proapoptotic peptide that acts on mitochondria, and ( iii ) multivalent presentation on iron oxide nanoparticles, which enhances the proapoptotic activity. The iron oxide component of the nanoparticles enabled imaging of GBM tumors in mice. Systemic treatment of GBM-bearing mice with the nanoparticles eradicated most tumors in one GBM mouse model and significantly delayed tumor development in another. Coinjecting the nanoparticles with a tumor-penetrating peptide further enhanced the therapeutic effect. Both models used have proven completely resistant to other therapies, suggesting clinical potential of our nanosystem.

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Section: Cgkrk Peptide Homes To Brain Tumors and Colocalizes With Mito-mentioning

confidence: 99%

Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma

Agemy

Friedmann‐Morvinski

Kotamraju

et al. 2011

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

Self Cite

323

309

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“…To prepare the tumor-bearing nude mouse model, female BALB/c nude mice were inoculated subcutaneously in the right armpits with 0.1 mL of MCF-7/ADR cell suspension (1×10 7 ).…”

Section: Materials and Methods Materialsmentioning

confidence: 99%

“…The experimental results obtained indicate that CREKA-modified nanoparticles accumulate in tumor vessels, where they induce additional local clotting and thereby produce new binding sites for more nanoparticles in tumor tissues without causing clotting in normal tissues. [7][8][9] Liposomes have been widely used as nanosize carriers in drug delivery systems for tumor therapy. 10 It is well known that pegylated liposomes can spontaneously accumulate in solid tumors via an enhanced permeability and retention effect through a passive targeting mechanism.…”

Section: Introductionmentioning

confidence: 99%

The antitumor activity of tumor-homing peptide-modified thermosensitive liposomes containing doxorubicin on MCF-7/ADR: in vitro and in vivo

Wang¹,

Wang²,

Zhong³

et al. 2015

IJN

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Clotted plasma proteins are present on the walls of tumor vessels and in tumor stroma. Tumor-homing peptide Cys-Arg-Glu-Lys-Ala (CREKA) could recognize the clotted plasma proteins in tumor vessels. Thermosensitive liposomes could immediately release the encapsulated drug in the vasculature of the heated tumor. In this study, we designed a novel form of targeted thermosensitive liposomes, CREKA-modified lysolipid-containing thermosensitive liposomes (LTSLs), containing doxorubicin (DOX) (DOX-LTSL-CREKA), to investigate the hypothesis that DOX-LTSL-CREKA might target the clotted plasma proteins in tumor vessels as well as tumor stroma and then exhibit burst release of the encapsulated DOX at the heated tumor site. We also hypothesized that the high local drug concentration produced by these thermosensitive liposomes after local hyperthermia treatment will be useful for treatment of multidrug resistance. The multidrug-resistant human breast adenocarcinoma (MCF-7/ADR) cell line was chosen as a tumor cell model, and the targeting and immediate release characteristics of DOX-LTSL-CREKA were investigated in vitro and in vivo. Furthermore, the antitumor activity of DOX-LTSL-CREKA was evaluated in MCF-7/ADR tumor-bearing nude mice in vivo. The targeting effect of the CREKA-modified thermosensitive liposomes on the clotted plasma proteins was confirmed in our in vivo imaging and immunohistochemistry experiments. The burst release of this delivery system was observed in our in vitro temperature-triggered DOX release and flow cytometry analysis and also by confocal microscopy experiments. The antitumor activity of the DOX-LTSL-CREKA was confirmed in tumor-bearing nude mice in vivo. Our findings suggest that the combination of targeting the clotted plasma proteins in the tumor vessel wall as well as tumor stroma by using CREKA peptide and temperature-triggered drug release from liposomes by using thermosensitive liposomes offers an attractive strategy for chemotherapeutic drug delivery to tumors.

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“…To evaluate the capability of tLyP-1 to deliver nanoparticles into tumors and penetrate into tumor tissue, we conjugated FAM-tLyP-1 to elongated iron oxide nanoparticles dubbed nanoworms (tLyP-1-NWs; dimensions: 30 Â 80-100 nm) (Park et al, 2009;Agemy et al, 2010). Iron oxide nanoparticles have the advantage that they can serve as a contrast agent in magnetic resonance imaging.…”

Section: Lyp-1 Internalization Uses the Cendr Pathwaymentioning

confidence: 99%

“…NWs coated with peptides were prepared as previously described (Park et al, 2009;Agemy et al, 2010).…”

Section: Peptides and Peptide-conjugated Nwsmentioning

confidence: 99%

Transtumoral targeting enabled by a novel neuropilin-binding peptide

et al. 2011

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We have recently described a class of peptides that improve drug delivery by increasing penetration of drugs into solid tumors. These peptides contain a C-terminal Cend Rule (CendR) sequence motif (R/K)XX(R/K), which is responsible for cell internalization and tissue-penetration activity. Tumor-specific CendR peptides contain both a tumor-homing motif and a cryptic CendR motif that is proteolytically unmasked in tumor tissue. A previously described cyclic tumor-homing peptide, LyP-1 (sequence: CGNKRTRGC), contains a CendR element and is capable of tissue penetration. We use here the truncated form of LyP-1, in which the CendR motif is exposed (CGNKRTR; tLyP-1), and show that both LyP-1 and tLyP-1 internalize into cells through the neuropilin-1-dependent CendR internalization pathway. Moreover, we show that neuropilin-2 also binds tLyP-1 and that this binding equally activates the CendR pathway. Fluorescein-labeled tLyP-1 peptide and tLyP-1-conjugated nanoparticles show robust and selective homing to tumors, penetrating from the blood vessels into the tumor parenchyma. The truncated peptide is more potent in this regard than the parent peptide LyP-1. tLyP-1 furthermore improves extravasation of a co-injected nanoparticle into the tumor tissue. These properties make tLyP-1 a promising tool for targeted delivery of therapeutic and diagnostic agents to breast cancers and perhaps other types of tumors.

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Nanoparticle-induced vascular blockade in human prostate cancer

Cited by 154 publications

References 30 publications

Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma

Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma

The antitumor activity of tumor-homing peptide-modified thermosensitive liposomes containing doxorubicin on MCF-7/ADR: in vitro and in vivo

Transtumoral targeting enabled by a novel neuropilin-binding peptide

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