Binding and transport of PAMAM‐RGD in a tumor spheroid model: The effect of RGD targeting ligand density

Waite, Carolyn L.; Roth, Charles M.

doi:10.1002/bit.23255

Cited by 40 publications

(40 citation statements)

References 30 publications

(49 reference statements)

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“…The different expression levels could be compared by the number of positive cells and were in accordance with previous reports (Kramer et al, 1991;Graeven et al, 2000;Pellet-Many et al, 2008;Yang et al, 2010). Previous researches showed the modifying density could affect the targeting efficiency of peptide ligand (Gu et al, 2008;Waite & Roth, 2011). The best density of iRGD for liposomal formulation was investigated by cellular uptake experiment.…”

Section: Preparation and Characterization Of Liposomessupporting

confidence: 84%

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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Section: Preparation and Characterization Of Liposomessupporting

confidence: 84%

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

et al. 2014

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“…We modeled NP diffusion into and out of the tumor spheroid, cell surface association and dissociation, and cellular internalization and externalization. Model parameters were fitted to experimental data of our silica NCs of 200, 50, and 20 nm in diameter (24), and best fit linear regression models were used to interpolate to NP sizes within this range (31)(32)(33)(34). Full details of our model, parameter fitting, and numerical solution techniques are provided in SI Appendix.…”

Section: Resultsmentioning

confidence: 99%

Investigating the optimal size of anticancer nanomedicine

Tang

Yang²,

Yin

et al. 2014

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

561

378

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Nanomedicines (NMs) offer new solutions for cancer diagnosis and therapy. However, extension of progression-free interval and overall survival time achieved by Food and Drug Administrationapproved NMs remain modest. To develop next generation NMs to achieve superior anticancer activities, it is crucial to investigate and understand the correlation between the physicochemical properties of NMs (particle size in particular) and their interactions with biological systems to establish criteria for NM optimization. Here, we systematically evaluated the size-dependent biological profiles of three monodisperse drug-silica nanoconjugates (NCs; 20, 50, and 200 nm) through both experiments and mathematical modeling and aimed to identify the optimal size for the most effective anticancer drug delivery. Among the three NCs investigated, the 50-nm NC shows the highest tumor tissue retention integrated over time, which is the collective outcome of deep tumor tissue penetration and efficient cancer cell internalization as well as slow tumor clearance, and thus, the highest efficacy against both primary and metastatic tumors in vivo.O ver the last two to three decades, consensus has been reached that the size of anticancer nanomedicines (NMs) plays a pivotal role in determining their biodistribution, tumor penetration, cellular internalization, and clearance from blood plasma and tissues as well as excretion from body, and thus, it has significant impact on overall therapeutic efficacy against cancers (1-7). Although most clinically approved anticancer NMs have size ranging from 100 to 200 nm (8, 9), recent studies showed that anticancer NMs with smaller sizes exhibited enhanced performance in vivo, such as greater tissue penetration and enhanced tumor inhibition, particularly those with size around or smaller than 50 nm (5-7, 10-12). As such, there has been a major push recently in the field of anticancer NM to miniaturize nanoparticle (NP) size using novel chemistry and engineering design (13-17). One unanswered question, however, is whether additional miniaturization of NM size would be necessary and result in additional improved anticancer efficacy. Widely evaluated small molecular therapeutics (<1,500 Da and <2 nm) can traverse most tumor tissues freely (18). However, they diffuse away from tumor tissues rapidly and get cleared primarily into tumor blood capillaries, leading to minimal tumor accumulation (18). Macromolecules of relatively low molecular masses (<40,000 Da and <10 nm) were also shown to have low overall tumor retention because of both rapid permeation into and clearance from tumor tissues, behaving to some extent like small molecule drugs (18,19). In conjunction with the renal clearance threshold (<10-15 nm) (20, 21) and interstitial/lymphatic fenestration (<20 nm) (22) for NPs, it becomes essential to carefully and comprehensively evaluate the in vivo behavior and anticancer efficacy of NMs in the size range of 20-50 nm to determine the optimal size of NM for cancer therapy.In this study, we used monodisper...

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“…For example, positive particles were taken up to a greater extent by proliferating cells, whereas negative particles were able to deliver drugs deep into tissues due to their ability to diffuse quickly (8). To enhance the nanoparticle delivery into the spheroid, arginine-glycine-aspartic acid peptide-conjugated dendrimers were developed, and they significantly enhanced the entry of dendrimer/siRNA nanoparticles into the U87 malignant glioma spheroid to improve siRNA delivery, which was presumably caused by the decreased integrin-binding affinity in the tumor model (32,33). In this study, 50 and 100 nm Au@tiopronin NPs with the same surface properties were prepared, and this ensured the possibility of the size effect on the penetration behavior in the tumor spheroid.…”

Section: Penetration Behavior Of Gold Nanoparticles Into Tumor Spheroidsmentioning

confidence: 99%

Superior Penetration and Retention Behavior of 50 nm Gold Nanoparticles in Tumors

et al. 2013

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Nanoparticles offer potential as drug delivery systems for chemotherapeutics based on certain advantages of molecular drugs. In this study, we report that particle size exerts great influence on the penetration and retention behavior of nanoparticles entering tumors. On comparing gold-coated Au@tiopronin nanoparticles that were prepared with identical coating and surface properties, we found that 50 nanoparticles were more effective in all in vitro, ex vivo, and in vivo assays conducted using MCF-7 breast cells as a model system. Beyond superior penetration in cultured cell monolayers, 50 nm Au@tiopronin nanoparticles also penetrated more deeply into tumor spheroids ex vivo and accumulated more effectively in tumor xenografts in vivo after a single intravenous dose. In contrast, larger gold-coated nanoparticles were primarily localized in the periphery of the tumor spheroid and around blood vessels, hindering deep penetration into tumors. We found multicellular spheroids to offer a simple ex vivo tumor model to simulate tumor tissue for screening the nanoparticle penetration behavior. Taken together, our findings define an optimal smaller size for nanoparticles that maximizes their effective accumulation in tumor tissue. Cancer Res; 73(1); 319-30. Ó2012 AACR.

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Binding and transport of PAMAM‐RGD in a tumor spheroid model: The effect of RGD targeting ligand density

Cited by 40 publications

References 30 publications

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

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

Investigating the optimal size of anticancer nanomedicine

Superior Penetration and Retention Behavior of 50 nm Gold Nanoparticles in Tumors

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