Passive and Active Tumour Targeting with Nanocarriers

Hirsjärvi, Samuli; Passirani, Catherine; Benoit, Jean‐Pierre

doi:10.2174/157016311796798991

Cited by 149 publications

(81 citation statements)

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“…7,8 The second is known as "active targeting", which may result in an even greater gradient of drug concentration between the intact and injured tissue due to the specific interaction of the tissue-recognition ligand engrafted on the surface of the carrier and a unique disease marker expressed either on the cell membrane or inside the cell. 9 This interaction results in accumulation of the drug-enriched nanocarrier in the tissue of interest with subsequent release of the drug during biodegradation of the particle coating.…”

Section: Introductionmentioning

confidence: 99%

Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles

Galagudza¹,

Королев²,

Постнов³

et al. 2012

IJN

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Pharmacological agents suggested for infarct size limitation have serious side effects when used at cardioprotective doses which hinders their translation into clinical practice. The solution to the problem might be direct delivery of cardioprotective drugs into ischemic-reperfused myocardium. In this study, we explored the potential of silica nanoparticles for passive delivery of adenosine, a prototype cardioprotective agent, into ischemic-reperfused heart tissue. In addition, the biodegradation of silica nanoparticles was studied both in vitro and in vivo. Immobilization of adenosine on the surface of silica nanoparticles resulted in enhancement of adenosine-mediated infarct size limitation in the rat model. Furthermore, the hypotensive effect of adenosine was attenuated after its adsorption on silica nanoparticles. We conclude that silica nanoparticles are biocompatible materials that might potentially be used as carriers for heart-targeted drug delivery.

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Section: Introductionmentioning

confidence: 99%

Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles

Galagudza¹,

Королев²,

Постнов³

et al. 2012

IJN

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“…For this latter purpose, antibodies or peptides are often conjugated to the surface of the particles. [19][20][21] The development of nanoparticles that combine these two functions, while highly desirable, has not received as much attention as that directed towards the synthesis of particles with separate functions.…”

Section: Introductionmentioning

confidence: 99%

Paclitaxel-loaded iron platinum stealth immunomicelles are potent MRI imaging agents that prevent prostate cancer growth in a PSMA-dependent manner

Taylor¹,

Sillerud²

2012

IJN

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Background and methods:Problems with the clinical management of prostate cancer include the lack of both specific detection and efficient therapeutic intervention. We report the encapsulation of superparamagnetic iron platinum nanoparticles (SIPPs) and paclitaxel in a mixture of polyethyleneglycolated, fluorescent, and biotin-functionalized phospholipids to create multifunctional SIPP-PTX micelles (SPMs) that were conjugated to an antibody against prostate-specific membrane antigen (PSMA) for the specific targeting, magnetic resonance imaging (MRI), and treatment of human prostate cancer xenografts in mice. Results: SPMs were 45.4 ± 24.9 nm in diameter and composed of 160.7 ± 22.9 µg/mL iron, 247.0 ± 33.4 µg/mL platinum, and 702.6 ± 206.0 µg/mL paclitaxel. Drug release measurements showed that, at 37°C, half of the paclitaxel was released in 30.2 hours in serum and two times faster in saline. Binding assays suggested that PSMA-targeted SPMs specifically bound to C4-2 human prostate cancer cells in vitro and released paclitaxel into the cells. In vitro, paclitaxel was 2.2 and 1.6 times more cytotoxic than SPMs to C4-2 cells at 24 and 48 hours of incubation, respectively. After 72 hours of incubation, paclitaxel and SPMs were equally cytotoxic. SPMs had MRI transverse relaxivities of 389 ± 15.5 Hz/mM iron, and SIPP micelles with and without drug caused MRI contrast enhancement in vivo. Conclusion: Only PSMA-targeted SPMs and paclitaxel significantly prevented growth of C4-2 prostate cancer xenografts in nude mice. Furthermore, mice injected with PSMA-targeted SPMs showed significantly more paclitaxel and platinum in tumors, compared with nontargeted SPM-injected and paclitaxel-injected mice.

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“…Therefore, efficient and site-specific delivery of therapeutic drugs is a critical challenge in the clinical treatment of cancer. Nanocarriers including liposomes, micelles and polymeric nanoparticles have been applied for tumor therapeutics by various mechanisms such as the enhanced permeability and retention (EPR) effect (Hirsjarvi et al, 2011). Conjugation of targeting ligands onto nanocarriers could further improve nanocarriers selective delivery to the tumor cell or the tumor vasculature (Zhang et al, 2010a,b;Arias, 2011;Xu et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

A new peptide ligand for colon cancer targeted delivery of micelles

Ren

Song

et al. 2015

Drug Delivery

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Ligands are an imperative part of targeted drug delivery systems, and choosing a ligand with high affinity is a subject of considerable interest. In this study, we first synthesized a 12-residue peptide (TK) that interacts with integrin a 6 b 1 overexpressed on colonic cancer cells. The molecular binding affinity assay indicated that TK had a high binding affinity for integrin a 6 b 1 . The results of cellular and tumor spheroid uptake suggested that TK peptide not only increases Caco-2 cells uptake, but also effectively increases penetration of the tumor spheroids. TK-conjugated PEG-PLA was synthesized to prepare a novel PEG-PLA micelles loading DOX or coumarin-6 (TK-MS/DOX or TK-MS/C6). The obtained TK-MS/DOX exhibited uniform, spherical shape with a size of 23.80 ± 0.32 nm and zeta potential of 12.21 ± 0.31 mV. The release behavior of DOX from micelles were observed no significant changes after TK modification, however, the release profile exhibited pH-sensitive properties. Compared with MS/DOX, TK-MS/DOX exhibited significantly stronger cytotoxicity for Caco-2. Confocal laser microscopy and flow cytometry data further indicated that the targeting micelles not only had higher uptake by Caco-2 cells, but also more effectively penetrated the tumor spheroids. Therefore, TK peptide appears to be suitable as a targeting ligand with potential applications in colonic targeted therapy. KeywordsColonic drug delivery, DOX, integrin a 6 b 1 receptor, micelles, peptide ligand History

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Passive and Active Tumour Targeting with Nanocarriers

Cited by 149 publications

References 0 publications

Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles

Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles

Paclitaxel-loaded iron platinum stealth immunomicelles are potent MRI imaging agents that prevent prostate cancer growth in a PSMA-dependent manner

A new peptide ligand for colon cancer targeted delivery of micelles

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