How Stealthy are PEG-PLA Nanoparticles? An NIR In Vivo Study Combined with Detailed Size Measurements

Schädlich, Andreas; Rose, C.; Kuntsche, Judith; Caysa, Henrike; Mueller, Thomas; Göpferich, Achim; Mäder, Karsten

doi:10.1007/s11095-011-0426-5

Cited by 50 publications

(63 citation statements)

References 49 publications

(61 reference statements)

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“…FRET-NPs were found to be stable in deionized water, with no significant changes in both the size and zeta potential for 7 days ( Figure 6A). 53 In addition, there was no observable change in the size of FRET-NPs that were stored in PBS only or 10% (v/v) of FBS in MEM media ( Figure 6B). However, in the presence of 4.5% (w/v) of BSA, the particles were slightly increased in size after 24 h. This could be due to the adsorption of proteins on the particle surfaces.…”

Section: ■ Results and Discussionmentioning

confidence: 94%

Development of Biocompatible Polymeric Nanoparticles for in Vivo NIR and FRET Imaging

2012

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The majority of near-infrared (NIR) fluorophores are organic molecules that show significant overlap between the excitation and emission spectra and therefore exhibit high fluorescence backgrounds during in vivo imaging. Recently, cyanine dyes with a large Stokes shift have shown great promise for NIR imaging but often undergo rapid photodegradation and nonspecific protein adsorption. Alternatively, fluorescence resonance energy transfer (FRET) is a promising technique to generate a larger gap between the excitation and emission maxima and thus can reduce the background signal. Here, we report the rational design of FRET-based polymeric nanoparticles for NIR and FRET imaging. The particles were assembled from diblock copolymers of poly(d,l-lactic-co-glycolic acid) and maleimide-activated poly(ethylene glycol), which were also encapsulated with both the donor (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocyanine) and acceptor (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine) fluorophores. Because of their extreme hydrophobicity, thousands of fluorophores could be encapsulated inside a single particle without causing leakage. FRET resulted in a large Stokes shift (>100 nm) of the emission maxima, and the transfer efficiency could be fine-tuned by further adjusting the doping ratio of the donor and acceptor fluorophores. The optimized formulation was less than 100 nm in size, brighter than quantum dots, stable in biological media, and demonstrated similar biodistribution to most nanomaterials. Additional animal phantom studies demonstrated that the FRET imaging platform developed could have far-reaching applications in optical imaging.

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Section: ■ Results and Discussionmentioning

confidence: 94%

Development of Biocompatible Polymeric Nanoparticles for in Vivo NIR and FRET Imaging

2012

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“…SSL-DiR and iRGD-SSL-DiR exhibited similar size distribution (134.9 ± 9.66 nm and 131.6 ± 11.6 nm, respectively) and zeta potential (À2.46 ± 0.85 mV and À3.19 ± 0.30 mV, respectively). As shown in Figure 5A, though liposomal formulations significantly improved circulation profiles and had EPR effect owing to PEG modification (Minko et al, 2006), there was high accumulation in liver and spleen as shown in the ex vivo image ( Figure 5B), possibly because of the arrestment of DiR-loaded formulations by RES system (Schädlich et al, 2011;Xiang et al, 2011). However, superior distribution of liposomes, especially iRGD-SSL-DiR at 12-h post-injection, in tumors could still be observed.…”

Section: Cytotoxicity Assaymentioning

confidence: 96%

A comprehensive study of iRGD-modified liposomes with improved chemotherapeutic efficacy on B16 melanoma

et al. 2014

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(2015) A comprehensive study of iRGD-modified liposomes with improved chemotherapeutic efficacy on B16 melanoma, Drug Delivery, 22:1, 10-20, DOI: 10.3109/10717544.2014 Here, iRGD-modified and doxorubicin-loaded sterically stabilized liposomes (iRGD-SSL-DOX) and passive liposomes (SSL-DOX) were prepared. A series of experiments were performed to evaluate the tissue penetration, cell penetration, tumor blood vessel damage and anti-tumor effect. The results of flow cytometry and confocal microscopy studies showed that iRGD-SSL-DOX with 5% DSPE-PEG 2000 -iRGD achieved higher cellular uptake level than that of SSL-DOX on B16 melanoma cells. iRGD-SSL-DOX also exhibited stronger cell growth inhibition in cytotoxicity experiments. The tumor penetrating effect of iRGD was further confirmed by imaging and cellular uptake studies in vivo, in which higher distribution of iRGD-modified liposomes in tumor tissue and tumor cells was observed. Moreover, iRGD-SSL-DOX displayed improved tumor growth inhibition and anti-angiogenesis with less systemic toxicity in an armpit B16 melanoma model. In conclusion, iRGD reserved its tumor-penetrating properties well when modified on the surface of liposomes at optimal density and iRGD-SSL-DOX would be a promising drug delivery system for active targeting tumor therapy.

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“…Although the high accumulation in liver and spleen was observed in the ex vivo images (Fig. 7B), which was possibly caused by the arrestment of DiR formulations by RES [36,37], more tumoral accumulation of SSL-DiR in the combinational regimen could also be noticed. Nanomedicines with a size around 100 nm, such as liposomes, could be effectively transported to tumors by EPR effect; however, they were found to distribute in a limited perivascular region and could not penetrate into tumor tissue further [38].…”

Section: Enhanced Liposomal Delivery Into Tumor By Decreasing Tumor Ifpmentioning

confidence: 96%

The reduction of tumor interstitial fluid pressure by liposomal imatinib and its effect on combination therapy with liposomal doxorubicin

Fan

et al. 2013

Biomaterials

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How Stealthy are PEG-PLA Nanoparticles? An NIR In Vivo Study Combined with Detailed Size Measurements

Cited by 50 publications

References 49 publications

Development of Biocompatible Polymeric Nanoparticles for in Vivo NIR and FRET Imaging

Development of Biocompatible Polymeric Nanoparticles for in Vivo NIR and FRET Imaging

A comprehensive study of iRGD-modified liposomes with improved chemotherapeutic efficacy on B16 melanoma

The reduction of tumor interstitial fluid pressure by liposomal imatinib and its effect on combination therapy with liposomal doxorubicin

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