Targeting of albumin-embedded paclitaxel nanoparticles to tumors

A significant barrier to the clinical translation of systemically administered therapeutic nanoparticles is their tendency to be removed from circulation by the mononuclear phagocyte system. The addition of a targeting ligand that selectively interacts with cancer cells can improve the therapeutic efficacy of nanomaterials, although these systems have met with only limited success. Here, we present a cooperative nanosystem consisting of two discrete nanomaterials. The first component is gold nanorod (NR) "activators" that populate the porous tumor vessels and act as photothermal antennas to specify tumor heating via remote near-infrared laser irradiation. We find that local tumor heating accelerates the recruitment of the second component: a targeted nanoparticle consisting of either magnetic nanoworms (NW) or doxorubicinloaded liposomes (LP). The targeting species employed in this work is a cyclic nine-amino acid peptide LyP-1 (Cys-Gly-Asn-Lys-Arg-ThrArg-Gly-Cys) that binds to the stress-related protein, p32, which we find to be upregulated on the surface of tumor-associated cells upon thermal treatment. Mice containing xenografted MDA-MB-435 tumors that are treated with the combined NR/LyP-1LP therapeutic system display significant reductions in tumor volume compared with individual nanoparticles or untargeted cooperative system. cancer therapy | gold nanorods | liposomes | magnetic nanoworms | protein expression

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“…S8). However, addition of the targeting ligand LyP-1 to the LP formulation slows tumor growth, in accord with previous work (27).…”

Section: Resultssupporting

confidence: 89%

“…relatively low therapeutic dose (3 mgDOX∕kg) is able to achieve significant tumor regression or elimination, which has not been observed in this tumor model with previous targeted therapies even with multiple high doses (27,28). For all the treatments studied in this work, no significant loss of body mass was observed.…”

Section: Resultsmentioning

confidence: 55%

Cooperative nanomaterial system to sensitize, target, and treat tumors

Park

Maltzahn²,

Xu³

et al. 2009

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

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287

232

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“…The presence of the cryptic CendR motif suggests the possibility of secondary binding to NRP1 (and perhaps to NRP2 in the lymphatics) and involvement of the CendR pathway. This hypothesis is supported by previous studies showing that LyP-1 is able to extravasate and penetrate the tumor parenchyma (Laakkonen et al, 2002;von Maltzahn et al, 2008;Karmali et al, 2009).…”

Section: Introductionsupporting

confidence: 82%

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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“…enhances significantly the anti-tumor activity of untargeted abraxane in mice, since the tumorhoming peptides facilitate the accumulation and penetration of the nanoparticles in tumors [534,536]. Similarly, the F3 peptide binds to nucleolin, a protein that is overexpressed on the surface of tumor endothelial cells [537].…”

Section: Peptidic Targetingmentioning

confidence: 99%

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Pérez-Herrero

Fernández‐Medarde

2015

European Journal of Pharmaceutics and Biopharmaceutics

1,396

754

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Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vasculatization and, in time, adquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastasic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, like the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic Código de campo cambiado

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Targeting of albumin-embedded paclitaxel nanoparticles to tumors

Cited by 203 publications

References 29 publications

Cooperative nanomaterial system to sensitize, target, and treat tumors

Cooperative nanomaterial system to sensitize, target, and treat tumors

Transtumoral targeting enabled by a novel neuropilin-binding peptide

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

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