Murine Models of Intraperitoneal Perfusion for Disseminated Colorectal Cancer

McCabe-Lankford, Eleanor; Peterson, Margarita; McCarthy, Bryce; Brown, April J.; Terry, Brad; Galarza-Paez, Laura

doi:10.1016/j.jss.2018.07.063

Cited by 8 publications

(19 citation statements)

References 43 publications

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“…The immunocompetent mouse line BALB/c, with its syngeneic undifferentiated colon carcinoma cell line (CT26), was used to induce a disseminated CRC model with peritoneal surface disease. Since disseminated abdominal cancers display high tumor numbers and tend to be poorly vascularized, HDAPPs were administered in vivo via an intraperitoneal injection or open abdominal perfusion as previously reported [29,30]. The aim of this work was to describe the functionalization, binding capabilities, and dynamic theranostic properties of HDAPPs for future disseminated cancer detection and treatment.…”

Section: Ivyspring International Publishermentioning

confidence: 99%

“…The disseminated colorectal cancer model was performed in accordance with a previously published method [30]. Six-week-old female BALB/c mice were anesthetized with 2% continuous vaporized isoflurane and injected intraperitoneally with 500 µL of 3× 10 6 CT26.WT.Fluc.Neo (CT26, passage 3-10) cells suspended in 1× PBS.…”

Section: Development Of the Disseminated Colorectal Cancer Modelmentioning

confidence: 99%

“…Once the disseminated tumors were established, mice underwent an open abdominal perfusion as previously described [30]. This technique is designed to mimic the peritoneal perfusion of chemotherapy that is delivered to human CRC patients during the HIPEC procedure.…”

Section: Nanoparticle Deliverymentioning

confidence: 99%

“…In order to minimize the duration of mouse surgeries, the minimal amount of time needed for optimal nanoparticle binding was determined in vitro and was found to be 30 minutes, which also correlates with human HIPEC perfusions that take anywhere from 30-to 120-minutes [30,38]. Binding of the HA-HDAPPs was assessed by a 30-minute incubation of the nanomaterials (non-coated HDAPPs and HA-HDAPPs) with CT26 cells.…”

Section: Cytotoxicity and Binding Of Hdapps In Vitro And Ex Vivomentioning

confidence: 99%

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Binding of Targeted Semiconducting Photothermal Polymer Nanoparticles for Intraperitoneal Detection and Treatment of Colorectal Cancer

McCabe-Lankford¹,

McCarthy²,

Berwick³

et al. 2020

Nanotheranostics

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Nanoparticles offer many promising advantages for improving current surgical regimens through their ability to detect and treat disseminated colorectal cancer (CRC). Hybrid Donor-Acceptor Polymer Particles (HDAPPs) have recently been shown to fluorescently detect and thermally ablate tumors in a murine model. Here, HDAPPS were functionalized with hyaluronic acid (HA) to improve their binding specificity to CT26 mouse CRC cells using HA to target the cancer stem cell marker CD44. In this work, we compared the binding of HA functionalized HDAPPs (HA-HDAPPs) in in vitro, ex vivo, and in vivo environments. The HA-HDAPPs bound to CT26 cells 2-fold more in vitro and 2.3-fold higher than un-functionalized HDAPPs ex vivo. Compared to intraoperative abdominal perfusion, intraperitoneal injection prior to laser stimulation for nanoparticle heat generation provides a superior modality of HA-HDAPPs delivery for CRC tumor selectivity. Photothermal treatment of disseminated CRC showed that only HA-HDAPPs delivered via intraperitoneal injection had a reduction in the tumor burden, and these nanoparticles also remained in the abdomen following resolution of the tumor. The results of this work confirm that HA-HDAPPs selectively bind to disseminated CRC, with ex vivo tumors having bound HA-HDAPPs capable of photothermal ablation. HA-HDAPPs demonstrated superior binding to tumor regions compared to HDAPPs. Overall, this study displays the theranostic potential of HDAPPs, emphasizing their capacity to detect and photothermally treat disseminated CRC tumors.

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Section: Ivyspring International Publishermentioning

confidence: 99%

Section: Development Of the Disseminated Colorectal Cancer Modelmentioning

confidence: 99%

Section: Nanoparticle Deliverymentioning

confidence: 99%

Section: Cytotoxicity and Binding Of Hdapps In Vitro And Ex Vivomentioning

confidence: 99%

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Binding of Targeted Semiconducting Photothermal Polymer Nanoparticles for Intraperitoneal Detection and Treatment of Colorectal Cancer

McCabe-Lankford¹,

McCarthy²,

Berwick³

et al. 2020

Nanotheranostics

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“…HDAPPs were utilized to evaluate photothermal-nanoparticlemediated hyperthermia with luciferase-based dosimetry in both CT26 parental and OxR cells. Absorption and fluorescence of HDAPPs are shown in Figure 2(A), where HDAPPs display a fluorescence quantum yield of 0.63%, which is sufficient to detect through 6 mm of tissue as shown by previous work in both tissue phantoms and in vivo [42,43]. The low quantum yield is indicative of a higher photothermal conversion efficiency (PCE), which was determined to be 51.2%.…”

Section: Demonstration Of Luminescent Monitoring Of Cell Effective Thmentioning

confidence: 55%

Oxaliplatin-resistant colorectal cancer models for nanoparticle hyperthermia

McCarthy

Singh

Levi‐Polyachenko

2021

International Journal of Hyperthermia

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Introduction: Metastatic colorectal cancer (CRC) is complicated by chemotherapy-resistant cell populations. Oxaliplatin is used in heated intraperitoneal hyperthermic chemoperfusion (HIPEC) for treatment of disseminated CRC. Photothermal nanoparticles can provide focal heating to improve the response of CRC cells to oxaliplatin, by confining heating near individual cells. Reduction in cellular luciferase signal may allow single-cell-resolution recording of thermal dosimetry. Methods: Oxaliplatin resistant (OxR) variants of luciferase-expressing CT26.WT-Fluc-Neo CRC cells were developed and their sensitivity to hyperthermia was evaluated. Polymer-based photothermal nanoparticles were developed, characterized and used to explore their potential for imparting a thermal dose to improve cell response to oxaliplatin. A correlation of thermal dose to intracellular luciferase activity was established using quantitative luminescence monitoring and microscopy. Results: Luciferase-based monitoring of thermal dose within CT26 cell lines was validated within the ranges of 0.04-8.33 CEM43 for parental cells and 0.05-9.74 CEM43 for OxR CT26 cells. This was further confirmed using nanoparticle-induced hyperthermia, where the single-cell resolution of the thermal dose can be achieved. The nanoparticles enhance cell killing of resistant cells when combined with oxaliplatin and stimulated to generate heat. Conclusion: Nanoparticle-based hyperthermia is effective for augmenting chemotherapy and can be coupled with reductions in CT26 luciferase expression to monitor thermal dose at single-cell resolution. The development of OxR CT26.WT-Fluc-Neo CRC cells sets the stage for pre-clinical evaluations to measure nanoparticle-induced hyperthermia to augment chemotherapy (Nano-HIPEC) in a chemotherapy-resistant model of disseminated CRC.

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Evaluation of the antitumour activity of local intraperitoneal hyperthermia in a model of advanced high-grade ovarian carcinoma in rats

et al. 2022

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In our study we carried out an exploratory assessment of the antitumor activity of hyperthermic intraperitoneal perfusion (Hipep) with 0.9 % sodium chloride solution and compared it with the effect of a single normothermic intraperitoneal (i.p.) Administration of cisplatin in the maximum tolerated dose (mtd). Thirty-six mature female Wistar rats with transplanted i.p. Syngeneic ovarian carcinoma were randomized into three groups: control group (2 ml of 0.9 % sodium chloride i.p. At room temperature, n=12); cisplatin group (cisplatin 4 mg/kg i.p. At room temperature, n=12); Hipep group (open i.p. Perfusion with 0.9 % sodium chloride solution at a temperature of 40,5–41,5 °c for 45 minutes, n=12). The primary endpoint was the overall survival (os) of the animals in each of the three groups. The total peritoneal cancer index (pci), weight and degree of ascites haemorrhagia were assessed at autopsy. The median os in the control group, Hipep, and cisplatin was 19, 39, and 40 days, respectively (log-rank test р<0.0001). In comparison to the control group, the differences were statistically significant for both cisplatin (HR=0.22; 95 % ci: 0.08–0.62; log-rank test р<0.0001) and Hipep (HR=0.32; 95 % ci 0.13–0.82; log-rank test р=0.0013). There were no differences in os between the cisplatin and Hipep groups (log-rank test р=0.4853). The Hipep procedure was associated with a significant decrease in total pci, a tendency towards a decrease in the ascites weight and a higher severity of haemorrhagia. In terms of os, local hyperthermia, provided by Hipep without a cytostatic drug, was comparable with single normothermic i.p. Administration of cisplatin in mtd and exceeded the effects of the latter in relation to the development of peritoneal carcinomatosis.

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Murine Models of Intraperitoneal Perfusion for Disseminated Colorectal Cancer

Cited by 8 publications

References 43 publications

Binding of Targeted Semiconducting Photothermal Polymer Nanoparticles for Intraperitoneal Detection and Treatment of Colorectal Cancer

Binding of Targeted Semiconducting Photothermal Polymer Nanoparticles for Intraperitoneal Detection and Treatment of Colorectal Cancer

Oxaliplatin-resistant colorectal cancer models for nanoparticle hyperthermia

Evaluation of the antitumour activity of local intraperitoneal hyperthermia in a model of advanced high-grade ovarian carcinoma in rats

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