Multi-responsive nanofibers composite gel for local drug delivery to inhibit recurrence of glioma after operation

Zhu, Y.; Jia, Jinping; Zhao, Gang; Huang, Xuyang; Wang, Lansheng; Zhang, Yongkang; Zhang, Long; Naveena, Konduru; Xie, Jun; Yu, Rutong; Liu, Hongmei

doi:10.1186/s12951-021-00943-z

Cited by 22 publications

(11 citation statements)

References 46 publications

(39 reference statements)

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“…A week after the injection of U87-MG-Red-FLuc cells into the mouse striatum, tumors underwent partial resection. Based on our previous set-up experiments and available published data 29 , the void in the tissue cavity was filled with 10 μL of cooled fluid gel which, upon hardening with increasing temperature up to 37 °C, was qualitatively confirmed to completely adhere to the cavity boundaries. Based on our previous estimation of a final active drug concentration of 3.5 mg/mL (see above), we calculated that the 10-μL amount of applied gel contained 35 μg of TMZ, corresponding to a final dose of approximately 1.75 mg/kg.…”

Section: Resultsmentioning

confidence: 94%

Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models

Gherardini

Buratti

Maturi

et al. 2023

Sci Rep

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Glioblastoma multiforme (GBM) is the most aggressive primary tumor of the central nervous system and the diagnosis is often dismal. GBM pharmacological treatment is strongly limited by its intracranial location beyond the blood–brain barrier (BBB). While Temozolomide (TMZ) exhibits the best clinical performance, still less than 20% crosses the BBB, therefore requiring administration of very high doses with resulting unnecessary systemic side effects. Here, we aimed at designing new negative temperature-responsive gel formulations able to locally release TMZ beyond the BBB. The biocompatibility of a chitosan-β-glycerophosphate-based thermogel (THG)-containing mesoporous SiO2 nanoparticles (THG@SiO2) or polycaprolactone microparticles (THG@PCL) was ascertained in vitro and in vivo by cell counting and histological examination. Next, we loaded TMZ into such matrices (THG@SiO2-TMZ and THG@PCL-TMZ) and tested their therapeutic potential both in vitro and in vivo, in a glioblastoma resection and recurrence mouse model based on orthotopic growth of human cancer cells. The two newly designed anticancer formulations, consisting in TMZ-silica (SiO2@TMZ) dispersed in the thermogel matrix (THG@SiO2-TMZ) and TMZ, spray-dried on PLC and incorporated into the thermogel (THG@PCL-TMZ), induced cell death in vitro. When applied intracranially to a resected U87-MG-Red-FLuc human GBM model, THG@SiO2-TMZ and THG@PCL-TMZ caused a significant reduction in the growth of tumor recurrences, when compared to untreated controls. THG@SiO2-TMZ and THG@PCL-TMZ are therefore new promising gel-based local therapy candidates for the treatment of GBM.

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Section: Resultsmentioning

confidence: 94%

Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models

Gherardini

Buratti

Maturi

et al. 2023

Sci Rep

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“…The development of molecular typing in gliomas has progressed rapidly based on the development of sequencing technology and bioinformatic technologies in recent years. Surgery is often unable to remove or completely resect the tumor because it is characterized by a highly invasive potential ability due to the aggressive growth of glioma and peripheral brain tissue, and residual tumor cells are difficult to be treated by radiation and chemotherapy thoroughly ( 28 , 29 ). New targets for therapeutic approaches are significant for improving the prognosis of patients with glioma.…”

Section: Discussionmentioning

confidence: 99%

A novel prognostic related lncRNA signature associated with amino acid metabolism in glioma

Yuan

Liu

et al. 2023

Front. Immunol.

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BackgroundGlioma is one of the deadliest malignant brain tumors in adults, which is highly invasive and has a poor prognosis, and long non-coding RNAs (lncRNAs) have key roles in the progression of glioma. Amino acid metabolism reprogramming is an emerging hallmark in cancer. However, the diverse amino acid metabolism programs and prognostic value remain unclear during glioma progression. Thus, we aim to find potential amino-related prognostic glioma hub genes, elaborate and verify their functions, and explore further their impact on glioma.MethodsGlioblastoma (GBM) and low-grade glioma (LGG) patients’ data were downloaded from TCGA and CCGA datasets. LncRNAs associated with amino acid metabolism were discriminated against via correlation analysis. LASSO analysis and Cox regression analysis were conducted to identify lncRNAs related to prognosis. GSVA and GSEA were performed to predict the potential biological functions of lncRNA. Somatic mutation data and CNV data were further built to demonstrate genomic alterations and the correlation between risk scores. Human glioma cell lines U251 and U87-MG were used for further validation in vitro experiments.ResultsThere were eight amino-related lncRNAs in total with a high prognostic value that were identified via Cox regression and LASSO regression analyses. The high risk-score group presented a significantly poorer prognosis compared with the low risk-score group, with more clinicopathological features and characteristic genomic aberrations. Our results provided new insights into biological functions in the above signature lncRNAs, which participate in the amino acid metabolism of glioma. LINC01561 is one of the eight identified lncRNAs, which was adopted for further verification. In in vitro experiments, siRNA-mediated LINC01561 silencing suppresses glioma cells’ viability, migration, and proliferation.ConclusionNovel amino-related lncRNAs associated with the survival of glioma patients were identified, and a lncRNA signature can predict glioma prognosis and therapy response, which possibly has vital roles in glioma. Meanwhile, it emphasized the importance of amino acid metabolism in glioma, particularly in providing deeper research at the molecular level.

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“…Furthermore, some nanomaterials can give hydrogels luminescence and imaging functions to better monitor drug release behavior [ 230 , 231 ]. For example, Zhu et al [ 232 ] developed an injectable MMPs- and ROS-responsive hydrogel. These hydrogels exhibited postoperative environmental responsiveness and achieved sustained temozolomide (TMZ) release in the surgical cavity.…”

Section: Discussionmentioning

confidence: 99%

Review targeted drug delivery systems for norcantharidin in cancer therapy

et al. 2022

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Norcantharidin (NCTD) is a demethylated derivative of cantharidin (CTD), the main anticancer active ingredient isolated from traditional Chinese medicine Mylabris. NCTD has been approved by the State Food and Drug Administration for the treatment of various solid tumors, especially liver cancer. Although NCTD greatly reduces the toxicity of CTD, there is still a certain degree of urinary toxicity and organ toxicity, and the poor solubility, short half-life, fast metabolism, as well as high venous irritation and weak tumor targeting ability limit its widespread application in the clinic. To reduce its toxicity and improve its efficacy, design of targeted drug delivery systems based on biomaterials and nanomaterials is one of the most feasible strategies. Therefore, this review focused on the studies of targeted drug delivery systems combined with NCTD in recent years, including passive and active targeted drug delivery systems, and physicochemical targeted drug delivery systems for improving drug bioavailability and enhancing its efficacy, as well as increasing drug targeting ability and reducing its adverse effects. Graphical Abstract

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Multi-responsive nanofibers composite gel for local drug delivery to inhibit recurrence of glioma after operation

Cited by 22 publications

References 46 publications

Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models

Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models

A novel prognostic related lncRNA signature associated with amino acid metabolism in glioma

Review targeted drug delivery systems for norcantharidin in cancer therapy

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