Local Delivery of Ferrociphenol Lipid Nanocapsules Followed by External Radiotherapy as a Synergistic Treatment Against Intracranial 9L Glioma Xenograft
Abstract:The synergistic effect between ferrociphenol-loaded LNCs and radiotherapy was due to a closely oxidative relationship. Upon these considerations, Fc-diOH-LNCs appear to be an efficient radiosensitive anticancer drug delivery system.
“…Another study confirms the reproducibility of the model as we obtained the same improvement in survival in the radiation group compared to the untreated group [18]. Therefore, this radiation therapy protocol has the potential to induce strong tumor debulking and facilitate concomitant chemotherapy treatment.…”
Section: Discussionsupporting
confidence: 75%
“…In his study, he tested a single high dose of radiation (ranging from 20 to 45 Gy) with radiosurgery in a limited volume. Previously, we investigated a radiation therapy schema in 3 fractionated doses of 6 Gy a week in vitro on 9L cell lines without and with concomitant chemotherapy [18]. The results showed that cell death was most important as the number of fractions increased from 1 to 3 and the increase was higher for the schemas associated with chemotherapy.…”
PurposeRadiotherapy has been shown to be an effective for the treatment human glioma and consists of 30 fractions of 2 Gy each for 6-7 weeks in the tumor volume with margins. However. in preclinical studies, many different radiation schedules are used. The main purpose of this work was to review the relevant literature and to propose an external whole-brain irradiation (WBI) protocol for a rat 9L glioma model.Materials and methods9L cells were implanted in the striatum of twenty 344-Fisher rats to induce a brain tumor. On day 8, animals were randomized in two groups: an untreated group and an irradiated group with three fractions of 6 Gy at day 8, 11 and 14. Survival and toxicity were assessed.ResultsIrradiated rats had significantly a longer survival (p = 0.01). No deaths occurred due to the treatment. Toxicities of reduced weight and alopecia were increased during the radiation period but no serious morbidity or mortality was observed. Moreover, abnormalities disappeared the week following the end of the therapeutic schedule.ConclusionsDelivering 18 Gy in 3 fractions of 6 Gy every 3 days, with mild anaesthesia, is safe, easy to reproduce and allows for standardisation in preclinical studies of different treatment regimens glioma rat model.
“…Another study confirms the reproducibility of the model as we obtained the same improvement in survival in the radiation group compared to the untreated group [18]. Therefore, this radiation therapy protocol has the potential to induce strong tumor debulking and facilitate concomitant chemotherapy treatment.…”
Section: Discussionsupporting
confidence: 75%
“…In his study, he tested a single high dose of radiation (ranging from 20 to 45 Gy) with radiosurgery in a limited volume. Previously, we investigated a radiation therapy schema in 3 fractionated doses of 6 Gy a week in vitro on 9L cell lines without and with concomitant chemotherapy [18]. The results showed that cell death was most important as the number of fractions increased from 1 to 3 and the increase was higher for the schemas associated with chemotherapy.…”
PurposeRadiotherapy has been shown to be an effective for the treatment human glioma and consists of 30 fractions of 2 Gy each for 6-7 weeks in the tumor volume with margins. However. in preclinical studies, many different radiation schedules are used. The main purpose of this work was to review the relevant literature and to propose an external whole-brain irradiation (WBI) protocol for a rat 9L glioma model.Materials and methods9L cells were implanted in the striatum of twenty 344-Fisher rats to induce a brain tumor. On day 8, animals were randomized in two groups: an untreated group and an irradiated group with three fractions of 6 Gy at day 8, 11 and 14. Survival and toxicity were assessed.ResultsIrradiated rats had significantly a longer survival (p = 0.01). No deaths occurred due to the treatment. Toxicities of reduced weight and alopecia were increased during the radiation period but no serious morbidity or mortality was observed. Moreover, abnormalities disappeared the week following the end of the therapeutic schedule.ConclusionsDelivering 18 Gy in 3 fractions of 6 Gy every 3 days, with mild anaesthesia, is safe, easy to reproduce and allows for standardisation in preclinical studies of different treatment regimens glioma rat model.
“…With our therapeutic tool based on the use of MIAMI cells, an increase in survival was obtained with a dose of Fc-diOH of about 3.6 µg/animal, as opposed to the 360 µg/animal reported for the convection-enhanced delivery of Fc-diOH-LNCs. 29,39 This drug delivery system is therefore very promising for improving the local tissue distribution of drugs in GBs and for limiting side effects.…”
Section: Discussionmentioning
confidence: 99%
“…Indeed, it has been reported that local irradiation may enhance the migration and engraftment specificity of MSCs, 42 in addition to potentiating the cytotoxic action of Fc-diOH. 39 …”
Recently developed drug delivery nanosystems, such as lipid nanocapsules (LNCs), hold great promise for the treatment of glioblastomas (GBs). In this study, we used a subpopulation of human mesenchymal stem cells, "marrow-isolated adult multilineage inducible" (MIAMI) cells, which have endogenous tumor-homing activity, to deliver LNCs containing an organometallic complex (ferrociphenol or Fc-diOH), in the orthotopic U87MG GB model. We determined the optimal dose of Fc-diOH-LNCs that can be carried by MIAMI cells and compared the efficacy of Fc-diOH-LNC-loaded MIAMI cells with that of the free-standing Fc-diOH-LNC system. We showed that MIAMI cells entrapped an optimal dose of about 20 pg Fc-diOH per cell, with no effect on cell viability or migration capacity. The survival of U87MG-bearing mice was longer after the intratumoral injection of Fc-diOH-LNC-loaded MIAMI cells than after the injection of Fc-diOH-LNCs alone. The greater effect of the Fc-diOH-LNC-loaded MIAMI cells may be accounted for by their peritumoral distribution and a longer residence time of the drug within the tumor. These results confirm the potential of combinations of stem cell therapy and nanotechnology to improve the local tissue distribution of anticancer drugs in GB.
“…The activity of the Fc-diOH-LNCs was evaluated in 9L cells in association with
radiotherapy (RT) and a combined treatment using the CED of Fc-diOH-LNCs with
external beam RT was evaluated in 9L glioma-bearing rats (35). For the combined RT, sucrose was dissolved in the aqueous
phase of the LNC suspension after formulation, to enhance the viscosity of the
infusion, and its presence did not affect the LNC size and had no toxic effect on
cells in vitro .…”
The application of nanotechnology to medicine can provide important benefits,
especially in oncology, a fact that has resulted in the emergence of a new field
called Nanooncology. Nanoparticles can be engineered to incorporate a wide
variety of chemotherapeutic or diagnostic agents. A nanocapsule is a vesicular
system that exhibits a typical core-shell structure in which active molecules
are confined to a reservoir or within a cavity that is surrounded by a polymer
membrane or coating. Delivery systems based on nanocapsules are usually
transported to a targeted tumor site and then release their contents upon change
in environmental conditions. An effective delivery of the therapeutic agent to
the tumor site and to the infiltrating tumor cells is difficult to achieve in
many cancer treatments. Therefore, new devices are being developed to facilitate
intratumoral distribution, to protect the active agent from premature
degradation and to allow its sustained and controlled release. This review
focuses on recent studies on the use of nanocapsules for cancer therapy and
diagnosis.
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