A Nanoparticle Size Series for In Vivo Fluorescence Imaging

Popović, Zoran V.; Liu, Wenhao; Chauhan, Vikash P.; Lee, Jungmin; Wong, Cliff; Greytak, Andrew B.; Insin, Numpon; Nocera, Daniel G.; Fukumura, Dai; Jain, Rakesh K.; Bawendi, Moungi G.

doi:10.1002/anie.201003142

Cited by 287 publications

(189 citation statements)

References 23 publications

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“…This is also recognized as a reason for the clinically approved Doxil (∼90 nm) only showing modest therapeutic benefits (27). In contrast, smaller nanoparticles show much better tumor penetration (27)(28)(29)(30), but very small particles typically suffer from short half-life time and insufficient tumor accumulation because of their rapid clearance (31,32). Therefore, an ideal delivery system should be relatively larger in its initial size to achieve longer circulation and selective extravasation (33), but once "docking" at tumor sites, it should be switchable to small particles to facilitate tumor penetration.…”

mentioning

confidence: 99%

Stimuli-responsive clustered nanoparticles for improved tumor penetration and therapeutic efficacy

et al. 2016

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

624

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A principal goal of cancer nanomedicine is to deliver therapeutics effectively to cancer cells within solid tumors. However, there are a series of biological barriers that impede nanomedicine from reaching target cells. Here, we report a stimuli-responsive clustered nanoparticle to systematically overcome these multiple barriers by sequentially responding to the endogenous attributes of the tumor microenvironment. The smart polymeric clustered nanoparticle (iCluster) has an initial size of ∼100 nm, which is favorable for long blood circulation and high propensity of extravasation through tumor vascular fenestrations. Once iCluster accumulates at tumor sites, the intrinsic tumor extracellular acidity would trigger the discharge of platinum prodrug-conjugated poly(amidoamine) dendrimers (diameter ∼5 nm). Such a structural alteration greatly facilitates tumor penetration and cell internalization of the therapeutics. The internalized dendrimer prodrugs are further reduced intracellularly to release cisplatin to kill cancer cells. The superior in vivo antitumor activities of iCluster are validated in varying intractable tumor models including poorly permeable pancreatic cancer, drug-resistant cancer, and metastatic cancer, demonstrating its versatility and broad applicability.nanomedicine | particle size | tumor penetration | tumor extracellular pH | stimuli responsive

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mentioning

confidence: 99%

Stimuli-responsive clustered nanoparticles for improved tumor penetration and therapeutic efficacy

et al. 2016

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

624

406

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“…The hydrodynamic size of nanomaterials influences their biological accessibility, local distribution, and clearance in a live animal, and it can affect the motion of the targeted species (12,13,18,19). To achieve sufficient transvascular permeability and interstitial diffusion, QD NB -Tz Ab was made as compact as possible by optimizing the incubation duration of QD NB with Tz Ab and quenching unreacted tetrazine on the antibodies using 5-norbornene-2,2-dimethanol to prevent additional aggregation.…”

Section: Significancementioning

confidence: 99%

“…These properties make QDs amenable to optical multiplexing for simultaneous study of various targets, long-term tracking, and deep-tissue imaging using multiphoton microscopy. Despite these exciting capabilities, most imaging studies using QDs have involved either in vitro targeting or ensemble measurements of QD signals over large volumes of tissue in vivo (11)(12)(13)(14)(15). This restriction is caused by a lack of technology for synthesizing QD conjugates that are optimal for single-cell imaging in vivo.…”

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confidence: 99%

Quantum dot/antibody conjugates for in vivo cytometric imaging in mice

Han¹,

Niemeyer

Huang

et al. 2015

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

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Multiplexed, phenotypic, intravital cytometric imaging requires novel fluorophore conjugates that have an appropriate size for long circulation and diffusion and show virtually no nonspecific binding to cells/serum while binding to cells of interest with high specificity. In addition, these conjugates must be stable and maintain a high quantum yield in the in vivo environments. Here, we show that this can be achieved using compact (∼15 nm in hydrodynamic diameter) and biocompatible quantum dot (QD) -Ab conjugates. We developed these conjugates by coupling whole mAbs to QDs coated with norbornene-displaying polyimidazole ligands using tetrazine–norbornene cycloaddition. Our QD immunoconstructs were used for in vivo single-cell labeling in bone marrow. The intravital imaging studies using a chronic calvarial bone window showed that our QD-Ab conjugates diffuse into the entire bone marrow and efficiently label single cells belonging to rare populations of hematopoietic stem and progenitor cells (Sca1+c-Kit+ cells). This in vivo cytometric technique may be useful in a wide range of structural and functional imaging to study the interactions between cells and between a cell and its environment in intact and diseased tissues.

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“…Therefore, very large particles ( > 100 nm in diameter) should be able to cross some of the blood vessels in hyper-permeable tumors but in low amounts. Furthermore, particles larger than 50 nm in diameter cannot penetrate deep into the tumor interstitial space (17), particularly in stromarich tumors, and will most likely cause only local effects. Taken together, we conclude that as far as transport is concerned the ideal particle size should be in the range of 12-50 nm.…”

Section: Design Considerationsmentioning

confidence: 99%

Intelligent drug delivery systems for the treatment of solid tumors

Stylianopoulos

2016

European Journal of Nanomedicine

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Abstract:The rationale for the use of nanoparticle formulations to treat cancer is based on the ability of these particles to facilitate selective delivery of drugs to the tumor site, reducing adverse effects and improving therapeutic outcomes. Current clinically approved nanomedicines have managed to reduce adverse effects significantly but the increase in overall survival is modest in many cases. Therefore, even though the goal of a better quality of life for the cancer patients has been achieved in large part, the increase in life expectancy still remains a critical challenge. Abnormalities in the tumor micro-environment prevent homogeneous distribution of nanoparticles to the interior of the tumor, decreasing the efficacy of the drug. Intelligent drug delivery systems offer new hope for overcoming these physiological barriers posed by the tumor and have the potential to provide more effective treatments. This review discusses the barriers to the delivery of nanomedicines to solid tumors, suggests design considerations that could optimize delivery and reviews promising intelligent drug delivery systems that have been developed to date.

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A Nanoparticle Size Series for In Vivo Fluorescence Imaging

Cited by 287 publications

References 23 publications

Stimuli-responsive clustered nanoparticles for improved tumor penetration and therapeutic efficacy

Stimuli-responsive clustered nanoparticles for improved tumor penetration and therapeutic efficacy

Quantum dot/antibody conjugates for in vivo cytometric imaging in mice

Intelligent drug delivery systems for the treatment of solid tumors

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