Synthetic nano-low density lipoprotein as targeted drug delivery vehicle for glioblastoma multiforme

Nikanjam, Mina; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Shu, Xiao Ou; Budinger, Thomas F.; Forte, Trudy M.

doi:10.1016/j.ijpharm.2006.07.046

Cited by 108 publications

(89 citation statements)

References 41 publications

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“…Thus the aim of the current study was to determine if sLDL maybe utilised as a drug targeting vector to ultimately deliver augmented doses of TKI into CML QSC to initiate apoptotic cell death. Interestingly, Nikanjam et al [23] demonstrated receptor mediated, targeted delivery of sLDL prepared according to our recipe to gliobastoma multiforme cell lines, following up with delivery of incorporated paclitaxel to the same brain tumour cell line model [37].…”

Section: Discussionmentioning

confidence: 98%

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Uptake of synthetic Low Density Lipoprotein by leukemic stem cells — a potential stem cell targeted drug delivery strategy

Zhou

Hatziieremia

Elliott

et al. 2010

Journal of Controlled Release

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Chronic myeloid leukemia (CML) stem/progenitor cells, which over-express Bcr-Abl, respond to imatinib by a reversible block in proliferation without significant apoptosis. As a result, patients are unlikely to be cured owing to the persistence of leukemic quiescent stem cells (QSC) capable of initiating relapse. Previously, we have reported that intracellular levels of imatinib in primary primitive CML cells (CD34 + 38 lo/-), are significantly lower than in CML progenitor cells (total CD34 + ) and leukemic cell lines. The aim of this study was to determine if potentially sub-therapeutic intracellular drug concentrations in persistent leukemic QSC may be overcome by targeted drug delivery using synthetic Low Density Lipoprotein (sLDL) particles. As a first step towards this goal, however, the extent of uptake of sLDL by leukemic cell lines and CML patient stem/progenitor cells was investigated. Results with non-drug loaded particles have shown an increased and preferential uptake of sLDL by Bcr-Abl positive cell lines in comparison to Bcr-Abl negative. Furthermore, CML CD34 + and primitive CD34 + 38 lo/-cells accumulated significantly higher levels of sLDL when compared with non-CML CD34 + cells. Thus, drug-loading the sLDL nanoparticles could potentially enhance intracellular drug concentrations in primitive CML cells and thus aid their eradication.

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Section: Discussionmentioning

confidence: 98%

“…sLDL can be routinely produced [18] that is physicochemically [20] and biologically [21] equivalent to native LDL. In addition sLDL has been employed to incorporate a range of drug payloads [22,23] and along with LDL therefore represent a proven class of drug targeting vector [24].…”

Section: Introductionmentioning

confidence: 99%

Uptake of synthetic Low Density Lipoprotein by leukemic stem cells — a potential stem cell targeted drug delivery strategy

Zhou

Hatziieremia

Elliott

et al. 2010

Journal of Controlled Release

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“…RLT could also facilitate the delivery of paclitaxel to glioblastoma multiforme cells and improve the efficacy of paclitaxel. 15,16 RLT-modified DNA nanocomplexes showed enhanced intracellular delivery of doxorubicin (Dox) and higher tumor cell inhibition. 17 In addition, in vivo studies confirmed that RLT increased the tumor accumulation of submicron emulsion and GNRs in mice.…”

Section: Introductionmentioning

confidence: 99%

Multifunctional gold nanorods and docetaxel-encapsulated liposomes for combined thermo- and chemotherapy

Hua¹,

Zhang

Liú³

et al. 2017

IJN

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Personalized and precise nanomedicines are highly demanded for today’s medical needs. Liposomes are ideal candidates for the construction of multifunctional drug delivery systems. In this study, a liposome was used to improve the clinical issues of docetaxel (Doc), a potent antimitotic chemotherapy for prostate cancer (PC). RLT, a low-density lipoprotein receptor (LDLR)-binding peptide, and PEG were conjugated to the liposomes, and gold nanorods (GNRs) were also incorporated into the liposomes. The GNRs/Doc-liposome-RLT (GNRs/DocL-R) was tested in PC-3 cells and in PC-3 tumor-bearing nude mice. Results showed that GNRs/DocL-R possessed a diameter approximately 163.15±1.83 nm and a zeta potential approximately −32.8±2.16 mV. GNRs/DocL-R showed enhanced intracellular entrance, increased accumulation in the implanted tumor region, and the highest tumor inhibition in vitro and in vivo. Therefore, the multifunctional GNRs/DocL-R was a potential cancer treatment via combined chemo- and thermotherapy.

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“…44 Many tumors overexpress the LDLr on the cell surface due to increased demand for cholesterol during membrane biogenesis faced by the rapidly proliferating cells. [45][46][47] The LDLr serves to capture extracellular sources of cholesterol via lipoproteins. In several cases, cancer patients suffer from various degrees of hypocholesterolemia, suggesting a strong inverse correlation between circulating plasma LDL level and the progression of the malignancy.…”

mentioning

confidence: 99%

Apolipoprotein E3-mediated cellular uptake of reconstituted high-density lipoprotein bearing core 3, 10, or 17 nm hydrophobic gold nanoparticles

Chuang¹,

Shon²,

Narayanaswami³

2017

IJN

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We have developed a high-density lipoprotein (HDL)-based platform for transport and delivery of hydrophobic gold nanoparticles (AuNPs). The ability of apolipoprotein E3 (apoE3) to act as a high-affinity ligand for the low-density lipoprotein receptor (LDLr) was exploited to gain entry of HDL with AuNPs into glioblastoma cells. AuNPs of 3, 10, and 17 nm diameter, the latter two synthesized by phase transfer process, were solubilized by integration with phospholipids and apoE3, yielding reconstituted HDL (rHDL) bearing AuNPs. Ultraviolet–visible spectra of rHDL-AuNP indicated the presence of stable particles with surface plasmon band at ~530 nm. Transmission electron microscopy (TEM) of rHDL-AuNP revealed roughly spherical particles with AuNPs embedded in the core. The rHDL-AuNP particles displayed robust binding to the LDLr and were internalized by receptor-mediated endocytosis in glioblastoma cells. Confocal microscopy confirmed cellular uptake of AuNPs in the endosomal–lysosomal compartments, while TEM revealed intracellular aggregated AuNPs. Cell viability assay demonstrated that >85% of cells were viable with rHDL-AuNP treatment of 0.1–100 μg/mL for 24 hours. These findings are significant since they offer an effective means of delivering AuNPs across the cell membrane, which is particularly relevant in tumor cells that overexpress LDLr.

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Synthetic nano-low density lipoprotein as targeted drug delivery vehicle for glioblastoma multiforme

Cited by 108 publications

References 41 publications

Uptake of synthetic Low Density Lipoprotein by leukemic stem cells — a potential stem cell targeted drug delivery strategy

Uptake of synthetic Low Density Lipoprotein by leukemic stem cells — a potential stem cell targeted drug delivery strategy

Multifunctional gold nanorods and docetaxel-encapsulated liposomes for combined thermo- and chemotherapy

Apolipoprotein E3-mediated cellular uptake of reconstituted high-density lipoprotein bearing core 3, 10, or 17 nm hydrophobic gold nanoparticles

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