Pericyte-Coverage of Human Tumor Vasculature and Nanoparticle Permeability

Zhang, Liuzhe; Nishihara, Hiroshi; Kano, Mitsunobu R.

doi:10.1248/bpb.35.761

Cited by 37 publications

(25 citation statements)

References 35 publications

(51 reference statements)

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“…Of note, EL1-luc/TAg transgenic mice may develop tumors with pericyte-covered vasculature, which has been strongly associated with reduced penetration of macromolecules and nanocarriers in solid tumors (40,41). Twenty-four hours after injection, DACHPt/m were found broadly distributed within the tumors, which can be associated with the prolonged blood circulation and high stability in the bloodstream of the micelles (24)(25)(26), as well as their densely PEGylated shielding and their relatively small diameter (30 nm) (25,26).…”

Section: Discussionmentioning

confidence: 99%

Targeted therapy of spontaneous murine pancreatic tumors by polymeric micelles prolongs survival and prevents peritoneal metastasis

Cabral¹,

Murakami²,

Hojo

et al. 2013

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

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Nanoscaled drug-loaded carriers are of particular interest for efficient tumor therapy as numerous studies have shown improved targeting and efficacy. Nevertheless, most of these studies have been performed against allograft and xenograft tumor models, which have altered microenvironment features affecting the accumulation and penetration of nanocarriers. Conversely, the evaluation of nanocarriers on genetically engineered mice, which can gradually develop clinically relevant tumors, permits the validation of their design under normal processes of immunity, angiogenesis, and inflammation. Therefore, considering the poor prognosis of pancreatic cancer, we used the elastase 1-promoted luciferase and Simian virus 40 T and t antigens transgenic mice, which develop spontaneous bioluminescent pancreatic carcinoma, and showed that long circulating micellar nanocarriers, incorporating the parent complex of oxaliplatin, inhibited the tumor growth as a result of their efficient accumulation and penetration in the tumors. The reduction of the photon flux from the endogenous tumor by the micelles correlated with the decrease of serum carbohydrate-associated antigen 19-9 marker. Micelles also reduced the incidence of metastasis and ascites, extending the survival of the transgenic mice.chemotherapy | drug delivery | (1,2-diaminocyclohexane)platinum (II)

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Section: Discussionmentioning

confidence: 99%

Targeted therapy of spontaneous murine pancreatic tumors by polymeric micelles prolongs survival and prevents peritoneal metastasis

Cabral¹,

Murakami²,

Hojo

et al. 2013

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

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“…The relationship between pericyte coverage and NP extravasation has been investigated in detail by various groups [1, 81–83]. Different from the initial assumption that all tumor microvessels have low and loose pericyte coverage [54], emerging evidence has demonstrated heterogeneous pericyte coverage within in one single tumor or with regards to different tumor types.…”

Section: Paradoxical Features Of the Tumor Microenvironment Impactimentioning

confidence: 99%

Exploring the Tumor Microenvironment with Nanoparticles

Miao

Huang

2015

Cancer Treatment and Research

105

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Recent developments in nanotechnology have brought new approaches to cancer diagnosis and therapy. While enhanced permeability and retention effect (EPR) promotes nanoparticle (NP) extravasation, the abnormal tumor vasculature, high interstitial pressure and dense stroma structure limit homogeneous intratumoral distribution of NP and compromise their imaging and therapeutic effect. Moreover, heterogeneous distribution of NP in nontumor-stroma cells damages the nontumor cells, and interferes with tumor-stroma crosstalk. This can lead to inhibition of tumor progression, but can also paradoxically induce acquired resistance and facilitate tumor cell proliferation and metastasis. Overall, the tumor microenvironment plays a crucial, yet controversial role in regulating NP distribution and their biological effects. In this review, we summarize recent studies on the stroma barriers for NP extravasation, and discuss the consequential effects of NP distribution in stroma cells. We also highlight design considerations to improve NP delivery and propose potential combinatory strategies to overcome acquired resistance induced by damaged stroma cells.

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“…Our results also indicate that although the extent of vascularity was not directly related to the tumor disposition of PEG liposomes, the vascular permeability within tumors substantially affected the tumor disposition of PEG liposomes and would be one of the major factors determining in vivo anti-tumor efficacy of PEG liposomal DOX, which was supported by the finding that the vascular permeability within C26 tumors assessed by Evans-blue extravasation assay was higher than that within other types of tumors. 24) Efficacy in the delivery of nanoparticles to pancreatic tumors is known to be very low 25) due to their poor vascular permeability compared with other solid tumors. 26) Thus, establishment of methods to enhance the vascular permeability within tumors may be highly beneficial to improve efficacy in the delivery of nanoparticles and the subsequent outcome of nanoparticle-based therapy for refractory cancer types such as pancreatic tumors.…”

Section: Determinants Of Epr Effect-driven Tumor Delivery Of Nanopartmentioning

confidence: 99%

Nanoparticle-Based Photodynamic Therapy: Current Status and Future Application to Improve Outcomes of Cancer Treatment

Ogawara

Higaki

2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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Photodynamic therapy (PDT) is an emerging cancer treatment that uses photosensitizers (PS), along with light to activate them, resulting in oxidation of various biological components in cancer tissues. However, since most potential PS are solubilized and given as aqueous solution, PS is non-specifically distributed in the body, leading to the induction of various side effects in normal tissues that are exposed to daylight such as skin and eyes. To overcome the problem associated with non-specific in vivo disposition of PS, various approaches have been applied to develop safer dosage forms for PS with more efficient tumor delivery and lower disposition to normal tissues. Passive drug targeting to tumors with nanoparticulate formulations has been recognized as one of the potentially useful approaches to improve the poor tissue specificity of conventional cancer chemotherapy and this approach should also be applicable for more efficient tumor delivery of PS. In this review article, several issues concerning the efficacy of PDT using nanoparticle-based formulations are discussed and our recent attempts to temporally enhance the vascular permeability within tumors with photodynamic treatment for the better therapeutic outcome of nanoparticle-based therapy are introduced.

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Pericyte-Coverage of Human Tumor Vasculature and Nanoparticle Permeability

Cited by 37 publications

References 35 publications

Targeted therapy of spontaneous murine pancreatic tumors by polymeric micelles prolongs survival and prevents peritoneal metastasis

Targeted therapy of spontaneous murine pancreatic tumors by polymeric micelles prolongs survival and prevents peritoneal metastasis

Exploring the Tumor Microenvironment with Nanoparticles

Nanoparticle-Based Photodynamic Therapy: Current Status and Future Application to Improve Outcomes of Cancer Treatment

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