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Rescuing apoptotic neurons in Alzheimer's disease using wheat germ agglutinin-conjugated and cardiolipin-conjugated liposomes with encapsulated nerve growth factor and curcumin.

Kuo YC, Lin CC - Int J Nanomedicine (2015)

Bottom Line: An increase in the CL mole percentage in lipids increased the liposomal diameter, absolute zeta potential value, entrapment efficiency of NGF and CUR, release of NGF, biocompatibility, and viability of SK-N-MC cells with Aβ(1-42), but decreased the atomic ratio of nitrogen to phosphorus and release of CUR.In addition, an increase in the WGA concentration for grafting enhanced the liposomal diameter, atomic ratio of nitrogen to phosphorus, and permeability of NGF and CUR across the blood-brain barrier, but reduced the absolute zeta potential value and biocompatibility.WGA-CL-liposomes carrying NGF and CUR could be promising colloidal delivery carriers for future clinical application in targeting the blood-brain barrier and inhibiting neurotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan, Republic of China.

ABSTRACT
Liposomes with cardiolipin (CL) and wheat germ agglutinin (WGA) were developed to permeate the blood-brain barrier and treat Alzheimer's disease. WGA-conjugated and CL-incorporated liposomes (WGA-CL-liposomes) were used to transport nerve growth factor (NGF) and curcumin (CUR) across a monolayer of human brain-microvascular endothelial cells regulated by human astrocytes and to protect SK-N-MC cells against apoptosis induced by β-amyloid1-42 (Aβ(1-42)) fibrils. An increase in the CL mole percentage in lipids increased the liposomal diameter, absolute zeta potential value, entrapment efficiency of NGF and CUR, release of NGF, biocompatibility, and viability of SK-N-MC cells with Aβ(1-42), but decreased the atomic ratio of nitrogen to phosphorus and release of CUR. In addition, an increase in the WGA concentration for grafting enhanced the liposomal diameter, atomic ratio of nitrogen to phosphorus, and permeability of NGF and CUR across the blood-brain barrier, but reduced the absolute zeta potential value and biocompatibility. WGA-CL-liposomes carrying NGF and CUR could be promising colloidal delivery carriers for future clinical application in targeting the blood-brain barrier and inhibiting neurotoxicity.

No MeSH data available.


Related in: MedlinePlus

Temporal variation in viability of Aβ1–42-incubated SK-N-MC cells after rescue with WGA-CL-NGF-CUR-liposomes.Notes: (A) Aβ1–42 at 5 μM; (B) Aβ1–42 at 10 μM. CWGA =5 mg/mL and rCL =20% (n=4). P<0.05 between CL-CUR-liposome group and free CUR group and between WGA-CL-NGF-CUR-liposome group and free CUR group after 24 hours.Abbreviations:PCV,SK-N-MC, viability of SK-N-MC cells after an insult with Aβ1–42 fibrils and treatment with WGA-CL-NGF-CUR-liposomes (%); CWGA, WGA concentration in grafting medium (mg/mL); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor; WGA, wheat germ agglutinin.
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f9-ijn-10-2653: Temporal variation in viability of Aβ1–42-incubated SK-N-MC cells after rescue with WGA-CL-NGF-CUR-liposomes.Notes: (A) Aβ1–42 at 5 μM; (B) Aβ1–42 at 10 μM. CWGA =5 mg/mL and rCL =20% (n=4). P<0.05 between CL-CUR-liposome group and free CUR group and between WGA-CL-NGF-CUR-liposome group and free CUR group after 24 hours.Abbreviations:PCV,SK-N-MC, viability of SK-N-MC cells after an insult with Aβ1–42 fibrils and treatment with WGA-CL-NGF-CUR-liposomes (%); CWGA, WGA concentration in grafting medium (mg/mL); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor; WGA, wheat germ agglutinin.

Mentions: Figure 9 shows the effect of WGA-CL-NGF-CUR-liposomes on the viability of SK-N-MC cells with Aβ1–42-induced cytotoxicity. As indicated in this figure, the viability of SK-N-MC cells decreased with time. In addition, treatment with WGA-CUR-liposomes for 24 and 36 hours significantly enhanced the viability of SK-N-MC cells. However, no significant difference was found between viability of SK-N-MC cells without treatment and that with free CUR. The order of cell viability was WGA-CL-NGF-CUR-liposomes >WGA-CL-CUR-liposomes > WGA-CUR-liposomes > free CUR ≈ no treatment. This manifested a neuroprotection of the current liposomal formulations against the degeneration induced by Aβ1–42. Comparing Figure 9A and B, the viability of SK-N-MC cells with Aβ1–42 5 μg/mL was higher than that with Aβ1–42 10 μg/mL. An explanation for these results is as follows. First, CUR could inhibit aggregation of Aβ1–42 and destroy Aβ1–42 fibrils.51 It has also been found that application of CUR for 7 days could reduce senile plaques in APPswe/PS1dE9 mice.52 Moreover, neuronal apoptosis associated with Aβ1–42 toxicity is commonly found in neuronal degeneration.53 In fact, the frequency of apoptosis in AD was found to be high because AD neurons were immunopositive for caspase 3.54 Also, c-Jun, a protein activated during the apoptotic cascade, is expressed in AD.55 Thus, encapsulation of CUR in WGA-CUR-liposomes can efficiently rescue SK-N-MC cells from apoptosis. Second, NGF plays an important role in neuronal survival and phenotypic maintenance. In an organotypic brain slice model, NGF was found to protect cholinergic neurons from degeneration.56 Third, CL has a high affinity for Aβ1–42 fibrils and its oligomers. It has been observed that CL enhances the viability of neuroblastoma cells due to its strong affinity for Aβ1–42.57 In this study, CL was included in the liposomal bilayer for Aβ1–42 binding, which was different from the targeting scheme reported in a recent publication.23 Fourth, SK-N-MC cells expressed several neurochemical markers, possessed typical cholinergic characteristics, and were recognized as a neuronal phenotype. Aβ1–42 fibrils are neurotoxic to SK-N-MC cells and have been used to induce neuronal apoptosis in an AD model.58 Although SK-N-MC cells were reported to be unresponsive to NGF, it was found later that SK-N-MC cells express neurotrophic tyrosine kinase receptor type 1, which is the major receptor for NGF.59–61 Thus, SK-N-MC cells could be responsive to NGF.45,62 In addition, an AD model could be established using an in vitro neuroblastoma cell line with a synthetic compound such as Aβ1–42.63 Since SK-N-MC cells are derived from neuroepithelioma, a culture of SK-N-MC cells with Aβ1–42 could represent AD.


Rescuing apoptotic neurons in Alzheimer's disease using wheat germ agglutinin-conjugated and cardiolipin-conjugated liposomes with encapsulated nerve growth factor and curcumin.

Kuo YC, Lin CC - Int J Nanomedicine (2015)

Temporal variation in viability of Aβ1–42-incubated SK-N-MC cells after rescue with WGA-CL-NGF-CUR-liposomes.Notes: (A) Aβ1–42 at 5 μM; (B) Aβ1–42 at 10 μM. CWGA =5 mg/mL and rCL =20% (n=4). P<0.05 between CL-CUR-liposome group and free CUR group and between WGA-CL-NGF-CUR-liposome group and free CUR group after 24 hours.Abbreviations:PCV,SK-N-MC, viability of SK-N-MC cells after an insult with Aβ1–42 fibrils and treatment with WGA-CL-NGF-CUR-liposomes (%); CWGA, WGA concentration in grafting medium (mg/mL); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor; WGA, wheat germ agglutinin.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4388084&req=5

f9-ijn-10-2653: Temporal variation in viability of Aβ1–42-incubated SK-N-MC cells after rescue with WGA-CL-NGF-CUR-liposomes.Notes: (A) Aβ1–42 at 5 μM; (B) Aβ1–42 at 10 μM. CWGA =5 mg/mL and rCL =20% (n=4). P<0.05 between CL-CUR-liposome group and free CUR group and between WGA-CL-NGF-CUR-liposome group and free CUR group after 24 hours.Abbreviations:PCV,SK-N-MC, viability of SK-N-MC cells after an insult with Aβ1–42 fibrils and treatment with WGA-CL-NGF-CUR-liposomes (%); CWGA, WGA concentration in grafting medium (mg/mL); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor; WGA, wheat germ agglutinin.
Mentions: Figure 9 shows the effect of WGA-CL-NGF-CUR-liposomes on the viability of SK-N-MC cells with Aβ1–42-induced cytotoxicity. As indicated in this figure, the viability of SK-N-MC cells decreased with time. In addition, treatment with WGA-CUR-liposomes for 24 and 36 hours significantly enhanced the viability of SK-N-MC cells. However, no significant difference was found between viability of SK-N-MC cells without treatment and that with free CUR. The order of cell viability was WGA-CL-NGF-CUR-liposomes >WGA-CL-CUR-liposomes > WGA-CUR-liposomes > free CUR ≈ no treatment. This manifested a neuroprotection of the current liposomal formulations against the degeneration induced by Aβ1–42. Comparing Figure 9A and B, the viability of SK-N-MC cells with Aβ1–42 5 μg/mL was higher than that with Aβ1–42 10 μg/mL. An explanation for these results is as follows. First, CUR could inhibit aggregation of Aβ1–42 and destroy Aβ1–42 fibrils.51 It has also been found that application of CUR for 7 days could reduce senile plaques in APPswe/PS1dE9 mice.52 Moreover, neuronal apoptosis associated with Aβ1–42 toxicity is commonly found in neuronal degeneration.53 In fact, the frequency of apoptosis in AD was found to be high because AD neurons were immunopositive for caspase 3.54 Also, c-Jun, a protein activated during the apoptotic cascade, is expressed in AD.55 Thus, encapsulation of CUR in WGA-CUR-liposomes can efficiently rescue SK-N-MC cells from apoptosis. Second, NGF plays an important role in neuronal survival and phenotypic maintenance. In an organotypic brain slice model, NGF was found to protect cholinergic neurons from degeneration.56 Third, CL has a high affinity for Aβ1–42 fibrils and its oligomers. It has been observed that CL enhances the viability of neuroblastoma cells due to its strong affinity for Aβ1–42.57 In this study, CL was included in the liposomal bilayer for Aβ1–42 binding, which was different from the targeting scheme reported in a recent publication.23 Fourth, SK-N-MC cells expressed several neurochemical markers, possessed typical cholinergic characteristics, and were recognized as a neuronal phenotype. Aβ1–42 fibrils are neurotoxic to SK-N-MC cells and have been used to induce neuronal apoptosis in an AD model.58 Although SK-N-MC cells were reported to be unresponsive to NGF, it was found later that SK-N-MC cells express neurotrophic tyrosine kinase receptor type 1, which is the major receptor for NGF.59–61 Thus, SK-N-MC cells could be responsive to NGF.45,62 In addition, an AD model could be established using an in vitro neuroblastoma cell line with a synthetic compound such as Aβ1–42.63 Since SK-N-MC cells are derived from neuroepithelioma, a culture of SK-N-MC cells with Aβ1–42 could represent AD.

Bottom Line: An increase in the CL mole percentage in lipids increased the liposomal diameter, absolute zeta potential value, entrapment efficiency of NGF and CUR, release of NGF, biocompatibility, and viability of SK-N-MC cells with Aβ(1-42), but decreased the atomic ratio of nitrogen to phosphorus and release of CUR.In addition, an increase in the WGA concentration for grafting enhanced the liposomal diameter, atomic ratio of nitrogen to phosphorus, and permeability of NGF and CUR across the blood-brain barrier, but reduced the absolute zeta potential value and biocompatibility.WGA-CL-liposomes carrying NGF and CUR could be promising colloidal delivery carriers for future clinical application in targeting the blood-brain barrier and inhibiting neurotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan, Republic of China.

ABSTRACT
Liposomes with cardiolipin (CL) and wheat germ agglutinin (WGA) were developed to permeate the blood-brain barrier and treat Alzheimer's disease. WGA-conjugated and CL-incorporated liposomes (WGA-CL-liposomes) were used to transport nerve growth factor (NGF) and curcumin (CUR) across a monolayer of human brain-microvascular endothelial cells regulated by human astrocytes and to protect SK-N-MC cells against apoptosis induced by β-amyloid1-42 (Aβ(1-42)) fibrils. An increase in the CL mole percentage in lipids increased the liposomal diameter, absolute zeta potential value, entrapment efficiency of NGF and CUR, release of NGF, biocompatibility, and viability of SK-N-MC cells with Aβ(1-42), but decreased the atomic ratio of nitrogen to phosphorus and release of CUR. In addition, an increase in the WGA concentration for grafting enhanced the liposomal diameter, atomic ratio of nitrogen to phosphorus, and permeability of NGF and CUR across the blood-brain barrier, but reduced the absolute zeta potential value and biocompatibility. WGA-CL-liposomes carrying NGF and CUR could be promising colloidal delivery carriers for future clinical application in targeting the blood-brain barrier and inhibiting neurotoxicity.

No MeSH data available.


Related in: MedlinePlus