Heteromultivalent ligand-decoration for actively targeted nanomedicine

Modery-Pawlowski, Christa L.; Gupta, Anirban Sen

doi:10.1016/j.biomaterials.2013.12.047

Cited by 36 publications

(38 citation statements)

References 87 publications

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“…Inspired by these molecular interactions, nanotechnologies have sought to mimic activated platelets by conjugating antibodies or peptide sequences that recognize cancer cells [33, 34]. Nevertheless, existing platelet biomimetic strategies represent a bottom-up approach and may have certain limitations: the bottom-up approach is largely inadequate in duplicating a complex protein makeup of natural platelets on a synthetic substrate.…”

Section: Resultsmentioning

confidence: 99%

Targeted drug delivery to circulating tumor cells via platelet membrane-functionalized particles

et al. 2016

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Circulating tumor cells (CTCs) are responsible for metastases in distant organs via hematogenous dissemination. Fundamental studies in the past decade have suggested that neutralization of CTCs in circulation could represent an effective strategy to prevent metastasis. Current paradigms of targeted drug delivery into a solid tumor largely fall into two main categories: unique cancer markers (e.g. overexpression of surface receptors) and tumor-specific microenvironment (e.g. low pH, hypoxia, etc.). While relying on a surface receptor to target CTCs can be greatly challenged by cancer heterogeneity, targeting of tumor microenvironments has the advantage of recognizing a broader spectrum of cancer cells regardless of genetic differences or tumor types. The blood circulation, however, where CTCs transit through, lacks the same tumor microenvironment as that found in a solid tumor. In this study, a unique “microenvironment” was confirmed upon introduction of cancer cells of different types into circulation where activated platelets and fibrin were physically associated with blood-borne cancer cells. Inspired by this observation, synthetic silica particles were functionalized with activated platelet membrane along with surface conjugation of tumor-specific apoptosis-inducing ligand cytokine, TRAIL. Biomimetic synthetic particles incorporated into CTC-associated micro-thrombi in lung vasculature and dramatically decreased lung metastases in a mouse breast cancer metastasis model. Our results demonstrate a “Trojan Horse” strategy of neutralizing CTCs to attenuate metastasis.

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Section: Resultsmentioning

confidence: 99%

Targeted drug delivery to circulating tumor cells via platelet membrane-functionalized particles

et al. 2016

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“…Dual-targeting of disease-specific markers can be advantageous compared to single targets by being more site-selective and having superior binding affinity. 50 …”

Section: Resultsmentioning

confidence: 99%

Shaping bio-inspired nanotechnologies to target thrombosis for dual optical-magnetic resonance imaging

et al. 2015

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Arterial and venous thrombosis are among the most common causes of death and hospitalization worldwide. Nanotechnology approaches hold great promise for molecular imaging and diagnosis as well as tissue-targeted delivery of therapeutics. In this study, we developed and investigated bioengineered nanoprobes for identifying thrombus formation; the design parameters of nanoparticle shape and surface chemistry, i.e. incorporation of fibrin-binding peptides CREKA and GPRPP, were investigated. Two nanoparticle platforms based on plant viruses were studied — icosahedral cowpea mosaic virus (CPMV) and elongated rod-shaped tobacco mosaic virus (TMV). These particles were loaded to carry contrast agents for dual-modality magnetic resonance (MR) and optical imaging, and both modalities demonstrated specificity of fibrin binding in vitro with the presence of targeting peptides. Preclinical studies in a carotid artery photochemical injury model of thrombosis confirmed thrombus homing of the nanoprobes, with the elongated TMV rods exhibiting significantly greater attachment to thrombi than icosahedral (sphere-like) CPMV. While in vitro studies confirmed fibrin-specificity conferred by the peptide ligands, in vivo studies indicated the nanoparticle shape had the greatest contribution toward thrombus targeting, with no significant contribution from either targeting ligand. These results demonstrate that nanoparticle shape plays a critical role in particle deposition at the site of vascular injury. Shaping nanotechnologies opens the door for the development of novel targeted diagnostic and therapeutic strategies (i.e., theranostics) for arterial and venous thrombosis.

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“…Surface treatment of nanocrystals may modify their biodistribution behavior [62,63]. FA surface-treated PIK-75 nanocrystals increased AUC 1.90-fold at the tumor site compared with nonmodified nanocrystals, while similar AUC values in liver, spleen and lung were observed by these two nanocrystals (Table 2) [32].…”

Section: Biodistributionmentioning

confidence: 90%

Developing Nanocrystals for Cancer Treatment

Lü

Cao

Gemeinhart

et al. 2015

Nanomedicine (Lond.)

113

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Nanocrystals are carrier-free solid drug particles that are sized in the nanometer range and have crystalline characteristics. Due to high drug loading (as high as 100%) - free of organic solvents or solubilizing chemicals - nanocrystals have become attractive in the field of drug delivery for cancer treatment. Top-down and bottom-up approaches have been developed for preparing anticancer nanocrystals. In this review, preparation methods and in vivo performance of anticancer nanocrystals are discussed first, followed by an introduction of hybrid nanocrystals in cancer theranostics.

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Heteromultivalent ligand-decoration for actively targeted nanomedicine

Cited by 36 publications

References 87 publications

Targeted drug delivery to circulating tumor cells via platelet membrane-functionalized particles

Targeted drug delivery to circulating tumor cells via platelet membrane-functionalized particles

Shaping bio-inspired nanotechnologies to target thrombosis for dual optical-magnetic resonance imaging

Developing Nanocrystals for Cancer Treatment

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