Thermosensitive magnetic liposomes for alternating magnetic field-inducible drug delivery in dual targeted brain tumor chemotherapy

Yu, Lijie; Chuang, Er Yuan; Cheng, Yu; Anilkumar, T.; Chen, Huai An; Chen, Jyh‐Ping

doi:10.1016/j.cej.2019.05.055

Cited by 71 publications

(43 citation statements)

References 42 publications

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“…It was shown that 2 h after injection, 20 nm gold nanoparticles had a broad biodistribution and a considerable accumulation within the brain. The possibility to apply steady and alternating magnetic fields to drive magnetic nanoparticles and liposomes across the BBB was also shown 21,40,51 .…”

Section: Discussionmentioning

confidence: 99%

Transport of ultrasmall gold nanoparticles (2 nm) across the blood–brain barrier in a six-cell brain spheroid model

Sokolova

Mekky

Meer

et al. 2020

Sci Rep

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The blood–brain barrier (BBB) is an efficient barrier for molecules and drugs. Multicellular 3D spheroids display reproducible BBB features and functions. The spheroids used here were composed of six brain cell types: Astrocytes, pericytes, endothelial cells, microglia cells, oligodendrocytes, and neurons. They form an in vitro BBB that regulates the transport of compounds into the spheroid. The penetration of fluorescent ultrasmall gold nanoparticles (core diameter 2 nm; hydrodynamic diameter 3–4 nm) across the BBB was studied as a function of time by confocal laser scanning microscopy, with the dissolved fluorescent dye (FAM-alkyne) as a control. The nanoparticles readily entered the interior of the spheroid, whereas the dissolved dye alone did not penetrate the BBB. We present a model that is based on a time-dependent opening of the BBB for nanoparticles, followed by a rapid diffusion into the center of the spheroid. After the spheroids underwent hypoxia (0.1% O2; 24 h), the BBB was more permeable, permitting the uptake of more nanoparticles and also of dissolved dye molecules. Together with our previous observations that such nanoparticles can easily enter cells and even the cell nucleus, these data provide evidence that ultrasmall nanoparticle can cross the blood brain barrier.

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Section: Discussionmentioning

confidence: 99%

Transport of ultrasmall gold nanoparticles (2 nm) across the blood–brain barrier in a six-cell brain spheroid model

Sokolova

Mekky

Meer

et al. 2020

Sci Rep

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“…The drop in magnetization strength may be associated with encapsulation of CMNPs within the liposomes, as the magnetization sensitivity may decline when the surfaces of CMNPs are occupied by lipids [ 43 , 44 ]. Nonetheless, decreased saturation magnetization may largely stem from the reduced weight percentage of CMNPs in MLs, as the magnetic moment is based on the unit weight of MLs, while all other components in MLs are diamagnetic [ 45 , 46 ]. This could be supported by comparing the expected saturation magnetization value of MLs (13.2 ± 1.0 emu/g), calculated from the loading percentage of CMNPs in MLs (21.8% ± 1.7%), and the value measured using SQUID analysis (13.0 emu/g).…”

Section: Resultsmentioning

confidence: 99%

“…The relative cell viability (%) was determined. The relative cell viability (%) was determined by the MTT assay in the same manner as before, with the viability of cells incubated with culture medium without particles taken as 100% [ 45 ].…”

Section: Methodsmentioning

confidence: 99%

Optimization of the Preparation of Magnetic Liposomes for the Combined Use of Magnetic Hyperthermia and Photothermia in Dual Magneto-Photothermal Cancer Therapy

Anilkumar

Chen

2020

IJMS

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In this work, we aimed to develop liposomal nanocomposites containing citric-acid-coated iron oxide magnetic nanoparticles (CMNPs) for dual magneto-photothermal cancer therapy induced by alternating magnetic field (AMF) and near-infrared (NIR) lasers. Toward this end, CMNPs were encapsulated in cationic liposomes to form nano-sized magnetic liposomes (MLs) for simultaneous magnetic hyperthermia (MH) in the presence of AMF and photothermia (PT) induced by NIR laser exposure, which amplified the heating efficiency for dual-mode cancer cell killing and tumor therapy. Since the heating capability is directly related to the amount of entrapped CMNPs in MLs, while the liposome size is important to allow internalization by cancer cells, response surface methodology was utilized to optimize the preparation of MLs by simultaneously maximizing the encapsulation efficiency (EE) of CMNPs in MLs and minimizing the size of MLs. The experimental design was performed based on the central composite rotatable design. The accuracy of the model was verified from the validation experiments, providing a simple and effective method for fabricating the best MLs, with an EE of 87% and liposome size of 121 nm. The CMNPs and the optimized MLs were fully characterized from chemical and physical perspectives. In the presence of dual AMF and NIR laser treatment, a suspension of MLs demonstrated amplified heat generation from dual hyperthermia (MH)–photothermia (PT) in comparison with single MH or PT. In vitro cell culture experiments confirmed the efficient cellular uptake of the MLs from confocal laser scanning microscopy due to passive accumulation in human glioblastoma U87 cells originated from the cationic nature of MLs. The inducible thermal effects mediated by MLs after endocytosis also led to enhanced cytotoxicity and cumulative cell death of cancer cells in the presence of AMF–NIR lasers. This functional nanocomposite will be a potential candidate for bimodal MH–PT dual magneto-photothermal cancer therapy.

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“…However, the major obstacle that hinders successful chemotherapy is its lack of selective targeting. Indeed, chemotherapeutic drugs may not be able to distinguish between normal and malignant cells, resulting in attacking healthy cells while killing cancer cells minimally [ 6 ]. Furthermore, multi-drug resistance and poor pharmacokinetic properties are other challenges that we are facing in cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Injectable Thermo-Sensitive Chitosan Hydrogel Containing CPT-11-Loaded EGFR-Targeted Graphene Oxide and SLP2 shRNA for Localized Drug/Gene Delivery in Glioblastoma Therapy

Lan

Chuang

et al. 2020

IJMS

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In this study, we aimed to develop a multifunctional drug/gene delivery system for the treatment of glioblastoma multiforme by combining the ligand-mediated active targeting and the pH-triggered drug release features of graphene oxide (GO). Toward this end, we load irinotecan (CPT-11) to cetuximab (CET)-conjugated GO (GO-CET/CPT11) for pH-responsive drug release after endocytosis by epidermal growth factor receptor (EGFR) over-expressed U87 human glioblastoma cells. The ultimate injectable drug/gene delivery system was designed by co-entrapping stomatin-like protein 2 (SLP2) short hairpin RNA (shRNA) and GO-CET/CPT11 in thermosensitive chitosan-g-poly(N-isopropylacrylamide) (CPN) polymer solution, which offers a hydrogel depot for localized, sustained delivery of the therapeutics after the in situ formation of CPN@GO-CET/CPT11@shRNA hydrogel. An optimal drug formulation was achieved by considering both the loading efficiency and loading content of CPT-11 on GO-CET. A sustained and controlled release behavior was found for CPT-11 and shRNA from CPN hydrogel. Confocal microscopy analysis confirmed the intracellular trafficking for the targeted delivery of CPT-11 through interactions of CET with EGFR on the U87 cell surface. The efficient transfection of U87 using SLP2 shRNA was achieved using CPN as a delivery milieu, possibly by the formation of shRNA/CPN polyplex after hydrogel degradation. In vitro cell culture experiments confirmed cell apoptosis induced by CPT-11 released from acid organelles in the cytoplasm by flow cytometry, as well as reduced SLP2 protein expression and inhibited cell migration due to gene silencing. Finally, in vivo therapeutic efficacy was demonstrated using the xenograft of U87 tumor-bearing nude mice through non-invasive intratumoral delivery of CPN@GO-CET/CPT11@shRNA by injection. Overall, we have demonstrated the novelty of this thermosensitive hydrogel to be an excellent depot for the co-delivery of anticancer drugs and siRNA. The in situ forming hydrogel will not only provide extended drug release but also combine the advantages offered by the chitosan-based copolymer structure for siRNA delivery to broaden treatment modalities in cancer therapy.

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Thermosensitive magnetic liposomes for alternating magnetic field-inducible drug delivery in dual targeted brain tumor chemotherapy

Cited by 71 publications

References 42 publications

Transport of ultrasmall gold nanoparticles (2 nm) across the blood–brain barrier in a six-cell brain spheroid model

Transport of ultrasmall gold nanoparticles (2 nm) across the blood–brain barrier in a six-cell brain spheroid model

Optimization of the Preparation of Magnetic Liposomes for the Combined Use of Magnetic Hyperthermia and Photothermia in Dual Magneto-Photothermal Cancer Therapy

Injectable Thermo-Sensitive Chitosan Hydrogel Containing CPT-11-Loaded EGFR-Targeted Graphene Oxide and SLP2 shRNA for Localized Drug/Gene Delivery in Glioblastoma Therapy

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