Vincristine and temozolomide combined chemotherapy for the treatment of glioma: a comparison of solid lipid nanoparticles and nanostructured lipid carriers for dual drugs delivery

Wu, Minxian; Fan, Yanghua; Lv, Shan; Xiao, Bing; Ye, Minhua; Zhu, Xingen

doi:10.3109/10717544.2015.1058434

Cited by 104 publications

(53 citation statements)

References 20 publications

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“…Moreover, gliomas have a high tendency to spread out into neighboring regions where they form satellite colonies [21]. In cases where neurosurgery is not applicable, chemotherapy is the first line primary treatment method for gliomas [5, 22]. However, the characteristics of tumor vascularization represent an obstacle for delivering therapeutics to tumors of the central nervous system due to challenged permeability and blood-brain barrier function [2, 23].…”

Section: Discussionmentioning

confidence: 99%

Cabazitaxel operates anti-metastatic and cytotoxic via apoptosis induction and stalls brain tumor angiogenesis

et al. 2016

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Taxanes target microtubules and are clinically established chemotherapeutic agents with proven efficacy in human cancers. Cabazitaxel (XRP-6258, Jevtana®) is a second generation semisynthetic taxane with high chemotherapeutic potential in prostate cancer. There, cabazitaxel can overcome docetaxel-resistant prostate cancer. Here, we tested the effects of cabazitaxel on glioma cells, and non-transformed cells such as neurons and astrocytes. Cabazitaxel operates highly toxic in various human glioma cells at nanomolar concentrations. In contrast, primary astrocytes and neurons are not affected by this agent. Cabazitaxel disrupts cytoskeletal F-actin fibers and induces apoptotic cell death in gliomas. Moreover, cabazitaxel displayed highest efficacy in inhibiting glioma cell migration and invasion. Here we demonstrate that cabazitaxel inhibited tumor migration already at 1 nM. We also tested cabazitaxel in the ex vivo VOGiM assay. Cabazitaxel stalled glioma growth and at the same time inhibited tumor-induced angiogenesis. In summary, we found that cabazitaxel operates as an apoptosis-inducing gliomatoxic agent with strongest effects on migration and invasive growth. Thus, our report uncovered cabazitaxel actions on gliomas and on the brain tumor microenvironment. These data reveal novel aspects for adjuvant approaches when applied to brain tumor patients.

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Section: Discussionmentioning

confidence: 99%

Cabazitaxel operates anti-metastatic and cytotoxic via apoptosis induction and stalls brain tumor angiogenesis

et al. 2016

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“…The morphology of NLCs was Figure S1 1 h NMr spectra. Notes: (A) PTX in DMsO-d 6 ; (B) 2′-succinyl-PTX in cDcl 3 ; (C) geM·hcl in DMsO-d 6 ; (D) 2′-succinyl-geM in DMsO-d 6 ; (E) PMagP-geM/PTX conjugates in DMsO-d 6 . Abbreviations: NMr, nuclear magnetic resonance; PTX, paclitaxel; DMsO, dimethyl sulfoxide; geM, gemcitabine; PMagP, poly(6-O-methacryloyl-d-galactopyranose).…”

Section: Characterization Of Nlcsmentioning

confidence: 99%

Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer

Liang

Tian

et al. 2017

IJN

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Gemcitabine (GEM) and paclitaxel (PTX) are effective combination anticancer agents against non-small-cell lung cancer (NSCLC). At the present time, a main challenge of combination treatment is the precision of control that will maximize the combined effects. Here, we report a novel method to load GEM (hydrophilic) and PTX (hydrophobic) into simplex tumor-targeted nanostructured lipid carriers (NLCs) for accurate control of the ratio of the two drugs. We covalently preconjugated the dual drugs through a hydrolyzable ester linker to form drug conjugates. N -acetyl- d -glucosamine (NAG) is a glucose receptor-targeting ligand. We added NAG to the formation of NAG-NLCs. In general, synthesis of poly(6- O -methacryloyl- d -galactopyranose)–GEM/PTX (PMAGP-GEM/PTX) conjugates was demonstrated, and NAG-NLCs were prepared using emulsification and solvent evaporation. NAG-NLCs displayed sphericity with an average diameter of 120.3±1.3 nm, a low polydispersity index of 0.233±0.04, and accurate ratiometric control over the two drugs. A cytotoxicity assay showed that the NAG-NLCs had better antitumor activity on NSCLC cells than normal cells. There was an optimal ratio of the two drugs, exhibiting the best cytotoxicity and combinatorial effects among all the formulations we tested. In comparison with both the free-drug combinations and separately nanopackaged drug conjugates, PMAGP-GEM/PTX NAG-NLCs (3:1) exhibited superior synergism. Flow cytometry and confocal laser scanning microscopy showed that NAG-NLCs exhibited higher uptake efficiency in A549 cells via glucose receptor-mediated endocytosis. This combinatorial delivery system settles problems with ratiometric coloading of hydrophilic and hydrophobic drugs for tumor-targeted combination therapy to achieve maximal anticancer efficacy in NSCLC.

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“…[27][28][29] They display distinctive features such as high drug loading, capability for modifications and conjugations, and so forth. [27][28][29] Solid lipid nanoparticles (SLNs) were established as alternative lipidbased nanocarriers such as emulsions, micelles, liposomes, and polymeric NPs. SLNs are composed of 0.1%-30% (w/w) lipids dispersed in an aqueous solution of 0.5%-5.0% (w/w) surfactant as stabilizing agent.…”

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confidence: 99%

Co-delivery of paclitaxel and TOS-cisplatin via TAT-targeted solid lipid nanoparticles with synergistic antitumor activity against cervical cancer

Liu¹,

Liang²,

Liu³

et al. 2017

IJN

104

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Background Cervical cancer is a major world health problem for women. Currently, cancer research focuses on improving therapy for cervical cancer using various treatment options such as co-delivery of chemotherapeutic agents by nanocarriers. Purpose The aim of this study was to develop trans-activating transcriptional activator (TAT)-modified solid lipid nanoparticles (SLNs) for co-delivery of paclitaxel (PTX) and α-tocopherol succinate-cisplatin prodrug (TOS-CDDP) (TAT PTX/TOS-CDDP SLNs) in order to achieve synergistic antitumor activity against cervical cancer. Methods Lipid prodrug of CDDP (TOS-CDDP) and TAT-containing polyethylene glycol-distearoyl-phosphatidylethanolamine (TAT-PEG-DSPE) were synthesized. TAT PTX/TOS-CDDP SLNs were prepared by emulsification and solvent evaporation method. Physicochemical characteristics of SLNs such as size, morphology, and release profiles were explored. In vitro and in vivo studies were carried out to assess the efficacy of their antitumor activity in target cells. Results TAT PTX/TOS-CDDP SLNs could be successfully internalized by HeLa cells and showed a synergistic effect in the suppression of cervical tumor cell growth. They exhibited high tumor tissue accumulation, superior antitumor efficiency, and much lower toxicity in vivo. Conclusion The present study indicates that the co-delivery system provides a promising platform as a combination therapy for the treatment of cervical cancer, and possibly other types of cancer as well.

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Vincristine and temozolomide combined chemotherapy for the treatment of glioma: a comparison of solid lipid nanoparticles and nanostructured lipid carriers for dual drugs delivery

Abstract: VT-NLCs can deliver VCR and TMZ into U87MG cells more efficiently, and inhibition efficacy is higher than VT-SLNs. This dual drugs-loaded NLCs could be an outstanding drug delivery system to achieve excellent therapeutic efficiency for the treatment of malignant gliomatosis cerebri.

Cited by 104 publications

References 20 publications

Cabazitaxel operates anti-metastatic and cytotoxic via apoptosis induction and stalls brain tumor angiogenesis

Cabazitaxel operates anti-metastatic and cytotoxic via apoptosis induction and stalls brain tumor angiogenesis

Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer

Co-delivery of paclitaxel and TOS-cisplatin via TAT-targeted solid lipid nanoparticles with synergistic antitumor activity against cervical cancer

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