Dendritic cell-mediated delivery of doxorubicin-polyglycerol-nanodiamond composites elicits enhanced anti-cancer immune response in glioblastoma

Li, Tong‐Fei; Li, Ké; Zhang, Quan; Wang, Chao; Yue, Yuan; Chen, Zhuo; Yuan, Shen-Jun; Liu, Xin; Wen, Yu; Han, Min; Komatsu, Naoki; Xu, Yunyun; Zhao, Li; Chen, Xiao

doi:10.1016/j.biomaterials.2018.07.035

Cited by 104 publications

(70 citation statements)

References 29 publications

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“…7). Similarly, the anti-proliferative effects of DOX loaded in catanionic solid lipid nanoparticles (CASLNs) 47 and DOX-polyglycerol-nanodiamond composites 48 were reported on U87 GBM cell line. For example, Kuo et al, 47 reported a greater anti-proliferative effect of DOX-CASLNs than that of free DOX due to the higher DOX accumulation in GBM cells through a vesicular uptake pathway.…”

Section: Cytotoxicity Of Dox-edt-ionps On Cancer Cell the Cytotoxicimentioning

confidence: 85%

Doxorubicin-loaded iron oxide nanoparticles for glioblastoma therapy: a combinational approach for enhanced delivery of nanoparticles

Norouzi

Yathindranath

Thliveris

et al. 2020

Sci Rep

207

116

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Although doxorubicin (DOX) is an effective anti-cancer drug with cytotoxicity in a variety of different tumors, its effectiveness in treating glioblastoma multiforme (GBM) is constrained by insufficient penetration across the blood-brain barrier (BBB). In this study, biocompatible magnetic iron oxide nanoparticles (IONPs) stabilized with trimethoxysilylpropyl-ethylenediamine triacetic acid (EDT) were developed as a carrier of DOX for GBM chemotherapy. The DOX-loaded EDT-IONPs (DOX-EDT-IONPs) released DOX within 4 days with the capability of an accelerated release in acidic microenvironments. The DOX-loaded EDT-IONPs (DOX-EDT-IONPs) demonstrated an efficient uptake in mouse brainderived microvessel endothelial, bEnd.3, Madin-Darby canine kidney transfected with multi-drug resistant protein 1 (MDCK-MDR1), and human U251 GBM cells. The DOX-EDT-IONPs could augment DOX's uptake in U251 cells by 2.8-fold and significantly inhibited U251 cell proliferation. Moreover, the DOX-EDT-IONPs were found to be effective in apoptotic-induced GBM cell death (over 90%) within 48 h of treatment. Gene expression studies revealed a significant downregulation of TOP II and Ku70, crucial enzymes for DNA repair and replication, as well as MiR-155 oncogene, concomitant with an upregulation of caspase 3 and tumor suppressors i.e., p53, MEG3 and GAS5, in U251 cells upon treatment with DOX-EDT-IONPs. An in vitro MDCK-MDR1-GBM co-culture model was used to assess the BBB permeability and anti-tumor activity of the DOX-EDT-IONPs and DOX treatments. While DOX-EDT-IONP showed improved permeability of DOX across MDCK-MDR1 monolayers compared to DOX alone, cytotoxicity in U251 cells was similar in both treatment groups. Using a cadherin binding peptide (ADTC5) to transiently open tight junctions, in combination with an external magnetic field, significantly enhanced both DOX-EDT-IONP permeability and cytotoxicity in the MDCK-MDR1-GBM co-culture model. Therefore, the combination of magnetic enhanced convective diffusion and the cadherin binding peptide for transiently opening the BBB tight junctions are expected to enhance the efficacy of GBM chemotherapy using the DOX-EDT-IONPs. In general, the developed approach enables the chemotherapeutic to overcome both BBB and multidrug resistance (MDR) glioma cells while providing site-specific magnetic targeting. Glioblastoma multiforme (GBM) is the most common and aggressive form of malignant gliomas whose current standard of care involves surgical recession followed by chemotherapy and radiotherapy 1,2. Nevertheless, the median survival of GBM patients who receive the current standard of care is 14.6 months post-diagnosis, and 5-year survival rate is only 9.8% 3 .

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Section: Cytotoxicity Of Dox-edt-ionps On Cancer Cell the Cytotoxicimentioning

confidence: 85%

Doxorubicin-loaded iron oxide nanoparticles for glioblastoma therapy: a combinational approach for enhanced delivery of nanoparticles

Norouzi

Yathindranath

Thliveris

et al. 2020

Sci Rep

207

116

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“…[31] As an alternative strategy to PEGylation, PG grafting and further derivatization of NDs have recently been developed to make the bioconjugation more convenient and economic (Scheme 6). [25,26] Theg rafted PG layer on NDs has ah yperbranched topology and possesses many hydroxyl groups at the periphery,w hich not only significantly improves the hydrophilicity,b ut can also be easily converted into more reactive functional groups (for example,amino,azido,and carboxylic groups) for further bioconjugation and drug loading.U pt o now,aw ide range of molecules including targeting peptides, [33] chemotherapeutics, [26,34] and plasmid DNA [35,36] have been conjugated to the surface-engineered ND-PG (Scheme 6), demonstrating preserved biological activities.…”

Section: Bioconjugationmentioning

confidence: 99%

Chemical Functionalization of Nanodiamonds: Opportunities and Challenges Ahead

et al. 2019

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Nanodiamond(ND)‐based technologies are flourishing in a wide variety of fields spanning from electronics and optics to biomedicine. NDs are considered a family of nanomaterials with an sp3 carbon core and a variety of sizes, shapes, and surfaces. They show interesting physicochemical properties such as hardness, stiffness, and chemical stability. Additionally, they can undergo ad‐hoc core and surface functionalization, which tailors them for the desired applications. Noteworthy, the properties of NDs and their surface chemistry are highly dependent on the synthetic method used to prepare them. In this Minireview, we describe the preparation of NDs from the materials‐chemistry viewpoint. The different methodologies of synthesis, purification, and surface functionalization as well as biomedical applications are critically discussed. New synthetic approaches as well as limits and obstacles of NDs are presented and analyzed.

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“…The grafted PG layer on NDs has a hyperbranched topology and possesses many hydroxyl groups at the periphery, which not only significantly improves the hydrophilicity, but can also be easily converted into more reactive functional groups (for example, amino, azido, and carboxylic groups) for further bioconjugation and drug loading. Up to now, a wide range of molecules including targeting peptides, chemotherapeutics, and plasmid DNA have been conjugated to the surface‐engineered ND‐PG (Scheme ), demonstrating preserved biological activities.…”

Section: Bioconjugationmentioning

confidence: 99%