항암 표적 물질로서의 TNF 관련 세포자가소멸 유도 단백질 (TRAIL)로 표면 수식된 인간 혈장 알부민(HSA) 나노입자의 제조와 평가 Preparation and evaluation of human serum albumin nanoparticles surfaced-modified with TNF-related apoptosis inducing Ligand(TRAIL) as an anti-tumor targeting agent원문보기
TNF 관련 세포자가소멸 유도 단백질 (TRAIL)은 죽음 수용체 (4/5)를 경유하여 다양한 암세포들에서 세포자가사멸을 유도하는 항암 단백질이다. 여기에서는, 표면에 TRAIL로 표면 수식된 인간 혈장 알부민 (...
TNF 관련 세포자가소멸 유도 단백질 (TRAIL)은 죽음 수용체 (4/5)를 경유하여 다양한 암세포들에서 세포자가사멸을 유도하는 항암 단백질이다. 여기에서는, 표면에 TRAIL로 표면 수식된 인간 혈장 알부민 (HSA)으로 만든 나노입자의 새로운 원형을 소개한다. 첫 번째로, HSA 나노입자는 HSA (50mg)를 증류수에 녹인 용액에 점적식으로 에탄올을 가한 후, 상호 연결 인자로 8% 글루타르알데하이드 용액을 가하는 개선된 코아세르베이션 기술로서 제조하였다. HSA-NPs의 표면 아민기는 pH 7.4에서 설폰-SMCC (30당량)으로 변경하고, 2-이미노사이올레인으로 먼저 수식한 TRAIL 용액을 가한 혼합액에 2시간 동안 pH 6.0에서 반응시켰다. 마지막으로, 독소루비신 (~300ug)과 제조된 TRAIL-HSA 나노입자를 배양하고 그것의 세포독성과 세포자가소멸 효과를 HCR116 세포와 MCF-7/ADR 세포에서 시험관내에서 평가했다. 새로운 형태의 TRAIL로 수식된 HSA 나노입자는 높은 수익률과 좁은 범위의 nano크기 (~220nm)를 보인다. 시험관내 세포독성 실험은 TRAIL로 수식된 HSA 나노입자가 좋은 암세포 표적 물질이 될 것이라는 것을 보여준다.
TNF 관련 세포자가소멸 유도 단백질 (TRAIL)은 죽음 수용체 (4/5)를 경유하여 다양한 암세포들에서 세포자가사멸을 유도하는 항암 단백질이다. 여기에서는, 표면에 TRAIL로 표면 수식된 인간 혈장 알부민 (HSA)으로 만든 나노입자의 새로운 원형을 소개한다. 첫 번째로, HSA 나노입자는 HSA (50mg)를 증류수에 녹인 용액에 점적식으로 에탄올을 가한 후, 상호 연결 인자로 8% 글루타르알데하이드 용액을 가하는 개선된 코아세르베이션 기술로서 제조하였다. HSA-NPs의 표면 아민기는 pH 7.4에서 설폰-SMCC (30당량)으로 변경하고, 2-이미노사이올레인으로 먼저 수식한 TRAIL 용액을 가한 혼합액에 2시간 동안 pH 6.0에서 반응시켰다. 마지막으로, 독소루비신 (~300ug)과 제조된 TRAIL-HSA 나노입자를 배양하고 그것의 세포독성과 세포자가소멸 효과를 HCR116 세포와 MCF-7/ADR 세포에서 시험관내에서 평가했다. 새로운 형태의 TRAIL로 수식된 HSA 나노입자는 높은 수익률과 좁은 범위의 nano크기 (~220nm)를 보인다. 시험관내 세포독성 실험은 TRAIL로 수식된 HSA 나노입자가 좋은 암세포 표적 물질이 될 것이라는 것을 보여준다.
TNF-related apoptosis inducing ligand (TRAIL) is an anti-cancer protein, which induces apoptosis in various cancer cells, via death receptors (DR4/5). Here, a new prototype of nanoparticles made of human serum albumin, which was conjugated with TRAIL on its surface, was introduced. First, HSA nanopa...
TNF-related apoptosis inducing ligand (TRAIL) is an anti-cancer protein, which induces apoptosis in various cancer cells, via death receptors (DR4/5). Here, a new prototype of nanoparticles made of human serum albumin, which was conjugated with TRAIL on its surface, was introduced. First, HSA nanoparticles (HSA-NPs) were prepared by a modified coacervation technique with a drop-wise ethanol addition to HSA solution (~50 mg) in DW, followed by a 8% glutaraldehyde solution for cross-linking. The surface-amine groups of HSA-NPs formed were then altered by the sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (Sulfo-SMCC; 30 eq.) at pH 7.4, and a Apo2L/TRAIL solution, which was previously modified with 2-iminothiolane, was allowed to react with this mixture at pH 6.0 for 2 h. A portion (~300 μg) of doxorubicin was incubated with the finally prepared TRAIL-HSA nanoparticles, and its cytotoxic and apoptotic effects were evaluated in the HCT116 cells and MCF-7/ADR cells in vitro. Results show that this new type of Apo2L/TRAIL-modified HSA-nanoparticles were prepared with a high yield and had narrow nano-sizes (~220 nm). The in vitro cytotoxicity shows that this Apo2L/TRAIL-HSA NPs would be a good cancer-targeting agent.
TNF-related apoptosis inducing ligand (TRAIL) is an anti-cancer protein, which induces apoptosis in various cancer cells, via death receptors (DR4/5). Here, a new prototype of nanoparticles made of human serum albumin, which was conjugated with TRAIL on its surface, was introduced. First, HSA nanoparticles (HSA-NPs) were prepared by a modified coacervation technique with a drop-wise ethanol addition to HSA solution (~50 mg) in DW, followed by a 8% glutaraldehyde solution for cross-linking. The surface-amine groups of HSA-NPs formed were then altered by the sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (Sulfo-SMCC; 30 eq.) at pH 7.4, and a Apo2L/TRAIL solution, which was previously modified with 2-iminothiolane, was allowed to react with this mixture at pH 6.0 for 2 h. A portion (~300 μg) of doxorubicin was incubated with the finally prepared TRAIL-HSA nanoparticles, and its cytotoxic and apoptotic effects were evaluated in the HCT116 cells and MCF-7/ADR cells in vitro. Results show that this new type of Apo2L/TRAIL-modified HSA-nanoparticles were prepared with a high yield and had narrow nano-sizes (~220 nm). The in vitro cytotoxicity shows that this Apo2L/TRAIL-HSA NPs would be a good cancer-targeting agent.
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