Receptor-Mediated Drug Delivery Systems Targeting to Glioma

Wang, Shanshan; Meng, Ying; Li, Chengyi; Qian, Min; Huang, Rongqin

doi:10.3390/nano6010003

Cited by 72 publications

(49 citation statements)

References 109 publications

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“…Moreover, nanomedicine applied through intracranial injection may have good chance to be sequestrated inside brain because of the effects of both folatetargeting and BBB-blocked washout. 32 Therefore, the therapeutic effect would probably be impaired if the direct delivery method is changed to systemic delivery. 33 Nevertheless, a careful selection of targeting molecules with high specificity is worthwhile in further systemic delivery studies.…”

Section: Discussionmentioning

confidence: 99%

Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment

Peng¹,

Huang²,

Xiao³

et al. 2018

IJN

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BackgroundThe treatment of glioma remains a challenge because conventional chemotherapy is often ineffective by drug resistance. Combinative therapy using chemotherapeutic agents and siRNA has demonstrated potential to improve anticancer outcome through a synergistic effect in various cancers. The current study aims to achieve better glioma treatment through a combinative therapy based on a folate-targeted nanocarrier carrying both temozolomide (TMZ) and anti-BCL-2 siRNA.MethodsA polymeric micelle (TMZ-FaPEC@siRNA) incorporating TMZ and anti-BCL-2 siRNA was prepared based on folate-conjugated triblock copolymer (Fa-PEG-PEI-PCL, Fa-PEC) of poly(ε-caprolactone) (PCL), poly(ethylenimine) (PEI) and poly(ethylene glycol) (PEG). The physicochemical properties and drug release profile of TMZ-FaPEC@siRNA were tested. The Fa-targeted drug delivery and joint effect of siRNA and TMZ to induce glioma apoptosis and tumor growth inhibition were evaluated both in vitro and in vivo.ResultsIn vitro cell study demonstrated that the nanocarrier effectively facilitates codelivery of siRNA and TMZ into C6 cells, resulting in a strong apoptotic response of cancer cells by silencing the antiapoptosis BCL-2 gene and activating the proapoptotic Bax gene simultaneously. In vivo study in rat bearing orthotropic glioma showed that tumor growth was inhibited and meanwhile animal survival was prolonged remarkably through intracranial injection of TMZ-FaPEC@siRNA.ConclusionOur results evidence the strong efficacy of the folate-targeted nanomedicine carrying TMZ and BCL-2 siRNA in treating glioma.

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Section: Discussionmentioning

confidence: 99%

Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment

Peng¹,

Huang²,

Xiao³

et al. 2018

IJN

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“…The drug delivery to brain faces has been considered difficult as the agents need to across the blood–brain barrier (BBB). However, a recent study has shown that the tight junction of the BBB loses the integrity by increasing permeability of the capillary endothelium [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein

Mahmud

Kasai

Khayrani

et al. 2018

IJMS

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We recently have established a successful xenograft model of human glioblastoma cells by enriching hyaluronic acid-dependent spheroid-forming populations termed U251MG-P1 cells from U251MG cells. Since U251MG-P1 cells have been confirmed to express CD44 along with principal stemness marker genes, OCT3/4, SOX2, KLF4 and Nanog, this CD44 expressing population appeared to majorly consist of undifferentiated cells. Evaluating the sensitivity to anti-cancer agents, we found U251MG-P1 cells were sensitive to doxorubicin with IC50 at 200 nM. Although doxorubicin has serious side-effects, establishment of an efficient therapy targeting undifferentiated glioblastoma cell population is necessary. We previously designed a chlorotoxin peptide fused to human IgG Fc region without hinge sequence (M-CTX-Fc), which exhibited a stronger growth inhibitory effect on the glioblastoma cell line A172 than an original chlorotoxin peptide. Combining these results together, we designed M-CTX-Fc conjugated liposomes encapsulating doxorubicin and used U251MG-P1 cells as the target model in this study. The liposome modified with M-CTX-Fc was designed with a diameter of approximately 100–150 nm and showed high encapsulation efficiency, adequate loading capacity of anticancer drug, enhanced antitumor effects demonstrating increasing uptake into the cells in vitro; M-CTX-Fc-L-Dox shows great promise in its ability to suppress tumor growth in vivo and it could serve as a template for targeted delivery of other therapeutics.

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“…Tf and Lf are quite similar in sequence and structure and coordinate iron in the same manner, but they differ in their affinities for iron as well as their receptor-binding properties [46]. While Tf is known to couple with Tf receptor, Lf is suggested to couple with its own receptor (Lf receptor) [47] but also with low-density lipoprotein receptor-related protein 1 (LRP1) and LRP2 [48]. U251-MG cells express TfR to a greater extent compared to their LRP1 or LRP2 expression and U87-MG expresses LRP1 and TfR (the protein atlas and [49,50]).…”

Section: Liposome Development and Characterizationmentioning

confidence: 99%

Design and Testing of Dual-Targeted Gd₃N@C80-Containing Glioblastoma Theranostics

Tedla

Plotkin

Dellinger

et al. 2019

Journal of Nanomaterials

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The majority of the malignant brain tumors are gliomas with glioblastoma being the most common and aggressive type. Due to its extreme infiltrative nature and higher occurrence frequency, finding new glioblastoma therapeutics and diagnostics is a high priority. In line with this, we previously synthesized a glioblastoma-targeting theranostic that images and delivers a therapeutic payload of doxorubicin (DXR) to human xenograft tumors. Herein, a dual-targeted theranostic is synthesized on the hypothesis that targeting multiple receptors would enhance delivery precision. Doxorubicin and endo-fullerene (Gd3N@C80) were encapsulated within liposomes and conjugated with transferrin (Tf) and lactoferrin (Lf). The hydrodynamic size, zeta potential, encapsulation efficiency, and tagging with proteins of the Gd3N@C80- and DXR-loaded liposomes were characterized using dynamic light scattering (DLS), inductively coupled plasma (ICP) mass spectrometer, Fourier-transform infrared spectroscopy (FTIR), and ultraviolet-visible (UV-Vis) spectrophotometry analysis. As verification of efficacy, the Tf and Lf dual-tagged theranostic liposomes were able to significantly induce cell death compared to Lf monotagged theranostics.

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Receptor-Mediated Drug Delivery Systems Targeting to Glioma

Cited by 72 publications

References 109 publications

Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment

Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment

Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein

Design and Testing of Dual-Targeted Gd₃N@C80-Containing Glioblastoma Theranostics

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Receptor-Mediated Drug Delivery Systems Targeting to Glioma

Cited by 72 publications

References 109 publications

Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment

Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment

Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein

Design and Testing of Dual-Targeted Gd3N@C80-Containing Glioblastoma Theranostics

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Design and Testing of Dual-Targeted Gd₃N@C80-Containing Glioblastoma Theranostics