TY  - JOUR
AB  - Background: Superparamagnetic iron oxide nanoparticles (SPIONs) have displayed multifunctional applications in cancer theranostics following systemic delivery. In an effort to increase the therapeutic potential of local therapies (including focal hyperthermia), nanoparticles can also be administered intratumorally. Therefore, the development of a reliable pharmacokinetic model for the prediction of nanoparticle distribution for both clinically relevant routes of delivery is of high importance.Materials and Methods: The biodistribution of SPIONs (of two different sizes - 130 nm and 60 nm) radiolabeled with zirconium-89 or technetium-99m following intratumoral or intravenous injection was investigated in C57/B16 mice bearing subcutaneous GL261 glioblastomas. Based on PET/CT biodistribution data, a novel pharmacokinetic model was established for a better understanding of the pharmacokinetics of the SPIONs after both administration routes.Results: The PET image analysis of the nanoparticles (confirmed by histology) demonstrated the presence of radiolabeled nanoparticles within the glioma site (with low amounts in the liver and spleen) at all investigated time points following intratumoral injection. The mathematical model confirmed the dynamic nanoparticle redistribution in the organism over a period of 72 h with an equilibrium reached after 100 h. Intravenous injection of nanoparticles demonstrated a different distribution pattern with a rapid particle retention in all organs (particularly in liver and spleen) and a subsequent slow release rate.Conclusion: The mathematical model demonstrated good agreement with experimental data derived from tumor mouse models suggesting the value of this tool to predict the real-time pharmacokinetic features of SPIONs in vivo. In the future, it is planned to adapt our model to other nanoparticle formulations to more precisely describe their biodistribution in in vivo model systems.
AU  - Klapproth, A.
AU  - Shevtsov, M*
AU  - Stangl, S.*
AU  - Li, W.B.
AU  - Multhoff, G.*
C1  - 59528
C2  - 48831
CY  - Po Box 300-008, Albany, Auckland 0752, New Zealand
SP  - 4677-4689
TI  - A new pharmacokinetic model describing the biodistribution of intraveneously and intratumorally administered superparamagnetic iron oxid nanoparticles (SPIONs) in a GL261 xenograft glioblastoma model.
JO  - Int. J. Nanomed.
VL  - 15
PB  - Dove Medical Press Ltd
PY  - 2020
SN  - 1176-9114
ER  - 

TY  - JOUR
AU  - Klapproth, A.
AU  - Shevtsov, M.*
AU  - Carter, T.J.*
AU  - Stangl, S.*
AU  - Chester, K.*
AU  - Li, W.B.
AU  - Multhoff, G.*
C1  - 59996
C2  - 49736
CY  - Po Box 300-008, Albany, Auckland 0752, New Zealand
SP  - 6067-6067
TI  - A new pharmacokinetic model describing the biodistribution of intravenously and intratumorally administered superparamagnetic iron oxide nanoparticles (SPIONs) in a GL261 xenograft glioblastoma model (vol 15, 4677, 2020).
JO  - Int. J. Nanomed.
VL  - 15
PB  - Dove Medical Press Ltd
PY  - 2020
SN  - 1176-9114
ER  - 

TY  - JOUR
AB  - Background: Intrapleural administration of compounds is a lung targeted, innovative therapeutic strategy for mesothelioma, which can be refined as a route for drug delivery that minimizes the potential for systemic toxicity. However, little is currently known about the retention of liposomal drugs at the site, after such topical administration. Purpose: To evaluate the retention of liposomes in lungs following intrapleural injection, and how this might be modulated by liposome properties and disease progression. Methods: DiR-incorporating liposomes with various lipid compositions and sizes were prepared, characterized (for size distribution and zeta potential) and injected intrapleurally in normal mice and mice with malignant pleural effusion (MPE). DiR retention in pleural cavity was followed by biofluorescence imaging. Results: Experimental results demonstrate that liposome size and PEG-coating, have a significant effect on residence time in the pleural cavity; negative surface charge does not. More than 20% liposomal-DiR is retained 24 d post-injection (in some cases), indicating the high potential towards localized diseases. Ex-vivo liposomal-DiR signal in tumors of MPE mice was similar to signal in liver, suggesting high tumor targeting potential of intrapleurally injected liposomes. Finally, no difference was noticed in liposomal-DiR retention between tumor-inoculated (MPE) and healthy mice, indicating the stability of liposomes in the presence of effusion (in MPE mice). Conclusion: The current study provides novel insights for using liposomes by intrapleural administration for the treatment of lung diseases.
AU  - Marazioti, A.*
AU  - Papadia, K.*
AU  - Giannou, A.*
AU  - Stathopoulos, G.T.
AU  - Antimisiaris, S.G.*
C1  - 56319
C2  - 46982
CY  - Po Box 300-008, Albany, Auckland 0752, New Zealand
SP  - 3773-3784
TI  - Prolonged retention of liposomes in the pleural cavity of normal mice and high tumor distribution in mice with malignant pleural effusion, after intrapleural injection.
JO  - Int. J. Nanomed.
VL  - 14
PB  - Dove Medical Press Ltd
PY  - 2019
SN  - 1176-9114
ER  - 

TY  - JOUR
AB  - Conjugated polymers (CPs) are upcoming optical contrast agents in view of their unique optical properties and versatile synthetic chemistry. Biofunctionalization of these polymer-based nanoparticles enables molecular imaging of biological processes. In this work, we propose the concept of using a biofunctionalized CP for noninvasive photoacoustic (PA) molecular imaging of breast cancer. In particular, after verifying the PA activity of a CP nano­particle (CP dots) in phantoms and the targeting efficacy of a folate-functionalized version of the same (folate-CP dots) in vitro, we systemically administered the probe into a folate receptor-positive (FR+ve) MCF-7 breast cancer xenograft model to demonstrate the possible application of folate-CP dots for imaging FR+ve breast cancers in comparison to CP dots with no folate moieties. We observed a strong PA signal at the tumor site of folate-CP dots-administered mice as early as 1 hour after administration as a result of the active targeting of the folate-CP dots to the FR+ve tumor cells but a weak PA signal at the tumor site of CP-dots-administered mice as a result of the passive accumulation of the probe by enhanced permeability and retention effect. We also observed that folate-CP dots produced ∼4-fold enhancement in the PA signal in the tumor, when compared to CP dots. These observations demonstrate the great potential of this active-targeting CP to be used as a contrast agent for molecular PA diagnostic imaging in various biomedical applications.
AU  - Balasundaram, G.*
AU  - Ho, C.J.H.*
AU  - Li, K.*
AU  - Driessen, W.H.P.
AU  - Dinish, U.S.*
AU  - Wong, C.L.*
AU  - Ntziachristos, V.
AU  - Liu, B.*
AU  - Olivo, M.C.D.*
C1  - 43155
C2  - 36031
CY  - Albany
SP  - 387-397
TI  - Molecular photoacoustic imaging of breast cancer using an actively targeted conjugated polymer.
JO  - Int. J. Nanomed.
VL  - 10
PB  - Dove Medical Press Ltd
PY  - 2015
SN  - 1176-9114
ER  - 

TY  - JOUR
AB  - BACKGROUND: Silica (SiO2) nanoparticles (NPs) are widely used in diverse industrial and biomedical applications. Their applicability depends on surface modifications, which can limit potential health problems. OBJECTIVE: To assess the potential impact of SiO2 NP exposure and NPs chemical modifications in allergic airway inflammation. METHODS: Mice were sensitized by five repetitive intraperitoneal injections of ovalbumin/aluminum hydroxide (1 μg) over 42 days, then intratracheally instilled with plain or modified SiO2 NPs (50 μg/mouse), and subsequently aerosol challenged for 20 minutes with ovalbumin. One or 5 days later, allergic inflammation was evaluated by cell differentiation of bronchoalveolar lavage fluid, lung function and gene expression and histopathology, as well as electron and confocal microscopy of pulmonary tissue. RESULTS: Plain SiO2 NPs induced proinflammatory and immunomodulatory effects in vivo, highlighted by enhanced infiltration of inflammatory cells in the bronchoalveolar lavage fluid, induction of a pulmonary T helper type 2 (Th2) cytokine pattern, differentiation of type 2 macrophages, and by morphological changes in the lung of sensitized mice. These effects were dramatically attenuated using surface-functionalized NPs with amino and phosphate groups, but not with polyethylene glycol. The role of macrophages in taking up SiO2 NPs was confirmed by flow cytometry, confocal microscopy, and gene expression analysis. CONCLUSION: Our data suggest that amino and phosphate surface modifications, but not polyethylene glycol (PEG), mitigate the proinflammatory and immunomodulatory effect of SiO2 NPs in allergic airway inflammation, paving the way for new strategies in the production of nanomaterials with lower health impact for humans.
AU  - Marzaioli, V.
AU  - Aguilar-Pimentel, J.A.
AU  - Weichenmeier, I.
AU  - Luxenhofer, G.
AU  - Wiemann, M.*
AU  - Landsiedel, R.*
AU  - Wohlleben, W.*
AU  - Eiden, S.*
AU  - Mempel, M.*
AU  - Behrendt, H.
AU  - Schmidt-Weber, C.B.
AU  - Gutermuth, J.
AU  - Alessandrini, F.
C1  - 31631
C2  - 34600
CY  - Albany
SP  - 2815-2832
TI  - Surface modifications of silica nanoparticles are crucial for their inert versus proinflammatory and immunomodulatory properties.
JO  - Int. J. Nanomed.
VL  - 9
IS  - 1
PB  - Dove Medical Press Ltd
PY  - 2014
SN  - 1176-9114
ER  -