Ultrasound-enhanced drug delivery in prostate cancer xenografts by nanoparticles stabilizing microbubbles

Eggen, Siv; Fagerland, Stein-Martin Tilrum; Mørch, Ýrr; Hansen, Rune; Søvik, Kishia; Berg, Sigrid; Furu, Håkon; Bøhn, Audun Dybvik; Lilledahl, Magnus B.; Angelsen, Anders; Angelsen, Bjørn; Davies, Catharina de Lange

doi:10.1016/j.jconrel.2014.05.020

Cited by 62 publications

(43 citation statements)

References 46 publications

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“…Immunohistochemical staining showed that mice treated with USMB demonstrated decreased cell proliferation and inhibited angiogenesis compared with the control group. The results of the present study indicated that USMB inhibits the growth of PC3 prostate cancer xenografts by inhibiting tumor cell proliferation and suppressing tumor angiogenesis, and this was consistent with the results of previous studies (33,34).…”

Section: A B C Discussionsupporting

confidence: 93%

“…This technique of using USMB to transiently enhance membrane permeability could lead to improved tumor cell drug internalization. Furthermore, USMB can cause the capillary wall to burst, and in this process, ruptured vessels introduce microbubbles into the intravascular space (33), making it easier to induce ultrasonic cavitation in the extracellular matrix, thus enhancing drug delivery further. As expected, in the present study, USMB combined with DTX showed greater growth inhibition when compared with USMB or DTX alone.…”

Section: A B C Discussionmentioning

confidence: 99%

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Low-frequency ultrasound-mediated microvessel disruption combined with docetaxel to treat prostate carcinoma xenografts in nude mice: A novel type of chemoembolization

et al. 2016

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Abstract. The aim of the present study was to investigate whether low-frequency ultrasound (US)-mediated microvessel disruption combined with docetaxel (DTX) can be used as a novel type of chemoembolization. Mice were assigned to four groups: i) The USMB group, treated with low-frequency US combined with microbubbles (USMB); ii) the DTX group, treated with DTX; iii) the USMB + DTX group, treated with combined therapy; and iv) the control group, which was untreated. Immediately after the first treatment, the average peak intensity (API) on contrast-enhanced US was calculated, and tumors were excised for hematoxylin and eosin (HE) staining. At 2 weeks post-treatment, the tumor volumes and wet weights were calculated, and tumors were excised for immunohistochemistry to calculate apoptotic index (AI), proliferative index (PI) and microvessel density (MVD) values. Immediately after the first treatment, in the DTX and control groups, the tumors demonstrated abundant perfusion enhancement, while in the USMB + DTX and USMB groups, blood perfusion of the tumors was interrupted. Compared with that of the control group, the API was significantly lower in the USMB + DTX USMB groups (all P<0.001). HE staining showed that tumor microvasculature was disrupted into flaky hematomas and severely dilated microvessels in the USMB + DTX and USMB groups. In the DTX and control groups, there was no distinct evidence of the disruption and dilation of blood microvessels. At the end of the treatment, the mean tumor inhibition ratio was 73.33, 46.67 and 33.33% for the USMB + DTX, DTX and USMB groups, respectively. The USMB + DTX group had the highest AI, and the lowest PI and MVD compared with the other groups, although the difference between the USMB + DTX and DTX groups with regard to PI and MVD was not significant (USMB + DTX vs. DTX group, P=0.345 and P=0.059, respectively). In conclusion, as a novel type of chemoembolization, USMB combined with DTX is more effective than USMB or DTX alone in inhibiting tumor growth via the enhancement of apoptosis, and the suppression of proliferation and angiogenesis.

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Section: A B C Discussionsupporting

confidence: 93%

Section: A B C Discussionmentioning

confidence: 99%

Low-frequency ultrasound-mediated microvessel disruption combined with docetaxel to treat prostate carcinoma xenografts in nude mice: A novel type of chemoembolization

et al. 2016

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“…In accordance with this, we have recently demonstrated that focused ultrasound improved the distribution of our NPs in prostate xenografts growing in athymic mice [3], and the improved distribution of NPs was due to both enhanced extravasation across the capillary wall and improved penetration through the extracellular matrix.…”

Section: Clinical Application Of the Np-mbssupporting

confidence: 84%

“…However, the uptake of NPs in tumors is often low and the distribution heterogeneous [2]. In recent years, ultrasound has been shown to enhance the delivery of various NPs to tumors in small animals [3][4][5]. Thus, ultrasound-mediated enhancement in delivery of NPs, which might be further enhanced in the presence of microbubbles (MBs), is clinically interesting.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle‐stabilized microbubbles for multimodal imaging and drug delivery

Mørch

Hansen

Berg

et al. 2015

Contrast Media & Molecular

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Microbubbles (MBs) are routinely used as contrast agents for ultrasound imaging. The use of ultrasound in combination with MBs has also attracted attention as a method to enhance drug delivery.We have developed a technology platform incorporating multiple functionalities, including imaging and therapy in a single system consisting of MBs stabilized by polyethylene glycol (PEG) coated polymeric nanoparticles (NPs). The NPs, containing lipophilic drugs and/or contrast agents, are composed of the widely used poly(butyl cyanoacrylate) (PBCA) polymer and prepared in a single step. MBs stabilized by these NPs are subsequently prepared by self-assembly of NPs at the MB air/liquid interface. Here we show that these MBs can act as contrast agents for conventional ultrasound imaging. Successful encapsulation of iron oxide NPs inside the PBCA NPs is demonstrated, potentially enabling the NPs/MBs to be used as magnetic resonance imaging (MRI) and/or molecular ultrasound imaging contrast agents. By precise tuning of the applied ultrasound pulse, the MBs burst and the NPs constituting the shell are released. This could result in increased local deposit of NPs into target tissue providing improved therapy and imaging contrast compared to freely distributed NPs.

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“…Balb/c nude mice (Shanghai Slack Laboratory Animal Co., Ltd., Shanghai, China) were purchased at 8 weeks of age and housed in ventilated cages at temperatures between 19 and 22 C and a relative humidity of 50-60% (Eggen et al, 2014). The animal experiments were performed according to the requirements of the National Act on the Use of Experimental Animals (P. R. China) and the protocols were approved by the Animal Ethics Committee of Shandong University.…”

Section: Cells and Animalsmentioning

confidence: 99%

Targeted nanomedicine for prostate cancer therapy: docetaxel and curcumin co-encapsulated lipid–polymer hybrid nanoparticles for the enhanced anti-tumor activityin vitroandin vivo

Wang²,

et al. 2015

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Chinese medicine is one nano-sized drug delivery system promising to generate synergistic anticancer effects, to maximize the treatment effect, and to overcome multi-drug resistance. The purpose of this study is to construct lipid-polymer hybrid nanoparticles (LPNs) as nanomedicine for co-encapsulation of DTX and curcumin (CUR). Methods: DTX and CUR co-encapsulated LPNs (DTX-CUR-LPNs) were constructed. DTX-CUR-LPNs were evaluated in terms of particles size, zeta potential, drug encapsulation, and drug delivery. The cytotoxicity of the LPNs was evaluated on PC-3 human prostate carcinoma cells (PC3 cells) by MTT assays. In vivo anti-tumor effects were observed on the PC3 tumor xenografts in mice.Results: The particle size of DTX-CUR-LPNs was 169.6 nm with a positive zeta potential of 35.7 mV. DTX-CUR-LPNs showed highest cytotoxicity and synergistic effect of two drugs in tumor cells in vitro. In mice-bearing PC-3 tumor xenografts, the DTX-CUR-LPNs inhibited tumor growth to a greater extent than other contrast groups, without inducing any obvious side effects. Conclusion: According to these results, the novel nanomedicine offers great promise for the dual drugs delivery to the prostate cancer cells, showing the potential of synergistic combination therapy for prostate cancer.

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Ultrasound-enhanced drug delivery in prostate cancer xenografts by nanoparticles stabilizing microbubbles

Cited by 62 publications

References 46 publications

Low-frequency ultrasound-mediated microvessel disruption combined with docetaxel to treat prostate carcinoma xenografts in nude mice: A novel type of chemoembolization

Low-frequency ultrasound-mediated microvessel disruption combined with docetaxel to treat prostate carcinoma xenografts in nude mice: A novel type of chemoembolization

Nanoparticle‐stabilized microbubbles for multimodal imaging and drug delivery

Targeted nanomedicine for prostate cancer therapy: docetaxel and curcumin co-encapsulated lipid–polymer hybrid nanoparticles for the enhanced anti-tumor activityin vitroandin vivo

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