Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size

Cabral, Horacio; Matsumoto, Yu; Mizuno, Kazue; Chen, Q.; Murakami, Mami; Kimura, Masanari; Terada, Yasuko; Kano, Mitsunobu R.; Miyazono, Kohei; Uesaka, Mitsuru; Nishiyama, Nobuhiro; Kataoka, Kazunori

doi:10.1038/nnano.2011.166

Cited by 2,118 publications

(1,853 citation statements)

References 33 publications

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“…The diameter of approximately 20 to 30 nm allows for movement through solid tumors (13,21) and the slightly negative ζ-potential at this size helps to minimize uptake by the mononuclear phagocyte system (22). CRLX101 is designed to have high solubility, to circulate and extravasate into solid tumors via their leaky vascular as an intact nanoparticle (13,15), to enter cancer cells, and to slowly release the active form of CPT for extended periods of time to enhance its mechanism of action (16).…”

Section: Discussionmentioning

confidence: 99%

Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle

Eliasof

Lazarus

Peters

et al. 2013

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

124

119

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Nanoparticles are currently being investigated in a number of human clinical trials. As information on how nanoparticles function in humans is difficult to obtain, animal studies that can be correlative to human behavior are needed to provide guidance for human clinical trials. Here, we report correlative studies on animals and humans for CRLX101, a 20-to 30-nm-diameter, multifunctional, polymeric nanoparticle containing camptothecin (CPT). CRLX101 is currently in phase 2 clinical trials, and human data from several of the clinical investigations are compared with results from multispecies animal studies. The pharmacokinetics of polymer-conjugated CPT (indicative of the CRLX101 nanoparticles) in mice, rats, dogs, and humans reveal that the area under the curve scales linearly with milligrams of CPT per square meter for all species. Plasma concentrations of unconjugated CPT released from CRLX101 in animals and humans are consistent with each other after accounting for differences in serum albumin binding of CPT. Urinary excretion of polymer-conjugated CPT occurs primarily within the initial 24 h after dosing in animals and humans. The urinary excretion dynamics of polymer-conjugated and unconjugated CPT appear similar between animals and humans. CRLX101 accumulates into solid tumors and releases CPT over a period of several days to give inhibition of its target in animal xenograft models of cancer and in the tumors of humans. Taken in total, the evidence provided from animal models on the CRLX101 mechanism of action suggests that the behavior of CRLX101 in animals is translatable to humans.nanomedicine | clinical translation | interspecies scaling | pharmacodynamics | Nanoparticles

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Section: Discussionmentioning

confidence: 99%

Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle

Eliasof

Lazarus

Peters

et al. 2013

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

124

119

View full text Add to dashboard Cite

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“…Functionalization of pre-made NPs presents difficulties with validation of uniform ligand density on nanoparticle surfaces and difficulties in scaleup of the conjugation reactions to commercial scale. This is especially important for optimizing cell targeting, as increasing ligand densities can improve binding in some instances, but excessively high-ligand densities can also result in decreased cell binding (Allen 2002;Cabral et al 2011;Cheng et al 2012;D'Addio et al 2013;Elias et al 2013;Kathleen et al 2007;Lee et al 2010). The FNP process enables the simultaneous encapsulation of several hydrophobic actives, including imaging modalities and hydrophobic drugs, to create theranostic NPs for novel antimicrobial treatments (Lu et al 2015(Lu et al , 2016(Lu et al , 2017Pansare et al 2012Pansare et al , 2014.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle targeting of Gram-positive and Gram-negative bacteria for magnetic-based separations of bacterial pathogens

Yang

Wilson

et al. 2017

Appl Nanosci

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Antimicrobial resistance is a healthcare problem of increasing significance, and there is increasing interest in developing new tools to address bacterial infections. Bacteria-targeting nanoparticles hold promise to improve drug efficacy, compliance, and safety. In addition, nanoparticles can also be used for novel applications, such as bacterial imaging or bioseperations. We here present the use of a scalable block-copolymer-directed self-assembly process, Flash NanoPrecipitation, to form zinc(II)-bis(dipicolylamine) modified nanoparticles that bind to both Grampositive and Gram-negative bacteria with specificity. Particles have tunable surface ligand densities that change particle avidity and binding efficacy. A variety of materials can be encapsulated into the core of the particles, such as optical dyes or iron oxide colloids, to produce imageable and magnetically active bacterial targeting constructs. As a proof-of-concept, these particles are used to bind and separate bacteria from solution in a magnetic column. Magnetic manipulation and separation would translate to a platform for pathogen identification or removal. These magnetic and targeted nanoparticles enable new methods to address bacterial infections.

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“…However, only particles in the range of 30 nm in diameter could penetrate into poorly permeable pancreatic tumors. 23 Also, only small molecules (9-40 nm in diameter) can pass through the nuclear envelop if they are to function inside the nucleus envelop. 24,25 One of the critical characteristics of nanoparticles as a drug delivery system is the ability to lower dose administration and thus toxcicity.…”

Section: Discussionmentioning

confidence: 99%

Milk derived colloid as a novel drug delivery carrier for breast cancer

Hayashi

Silanikove

Chang

et al. 2015

Cancer Biology & Therapy

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Triple negative breast cancer has an extremely poor prognosis when chemotherapy is no longer effective. To overcome drug resistance, novel drug delivery systems based on nanoparticles have had remarkable success. We produced a novel nanoparticle component 'MDC' from milk-derived colloid. In order to evaluate the anti-cancer effect of MDC, we conducted in vitro and in vivo experiments on cancer cell lines and a primary tumor derived breast xenograft. Doxorubicin (Dox) conjugated to MDC (MDC-Dox) showed higher cancer cell growth inhibition than MDC alone especially in cell lines with high EGFR expression. In a mouse melanoma model, MDC-Dox significantly suppressed tumor growth when compared with free Dox. Moreover, in a primary tumor derived breast xenograft, one of the mice treated with MDC-Dox showed partial regression, while mice treated with free Dox failed to show any suppression of tumor growth. We have shown that a novel nanoparticle compound made of simple milk-derived colloid has the capability for drug conjugation, and serves as a tumor-specific carrier of anti-cancer drugs. Further research on its safety and ability to carry various anti-cancer drugs into multiple drug-resistant primary breast models is warranted.

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Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size

Cited by 2,118 publications

References 33 publications

Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle

Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle

Nanoparticle targeting of Gram-positive and Gram-negative bacteria for magnetic-based separations of bacterial pathogens

Milk derived colloid as a novel drug delivery carrier for breast cancer

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