Name: synthesis of aptamer-pei-g-peg modified gold nanoparticles loaded with doxorubicin for targeted drug delivery
Uploaded: 2020-06-23T13:30:00
Description: Watch this Scientific Journal Video about Synthesis of Aptamer-PEI-g-PEG Modified Gold Nanoparticles Loaded with Doxorubicin for Targeted Drug Delivery at JoVE.com

이 연구는 중국의 국립 자연 과학 재단에 의해 투자되었다 (31700840); 허난성의 주요 과학 연구 프로젝트 (18B430013, 18A150049). 이 연구는 XYNU의 젊은 학자를위한 난후 학자 프로그램에 의해 지원되었다. 저자는 그의 도움이 작품에 대한 XYNU생명과학대학의 학사 학생 제보 Qu에게 감사를 표하고 싶습니다. 저자는 장비 사용에 대한 XYNU의 분석 및 테스트 센터를 인정하고 싶습니다.

주의: 모든 화학 물질을 사용하기 전에 모든 관련 재료 안전 데이터 시트(MSDS)를 참조해야 합니다. 중합체 및 나노 입자를 준비하는 데 사용되는 화학 물질의 몇 가지는 급성 독성이 있습니다. 나노 입자는 또한 잠재적인 위험이 있습니다. 장갑, 실험실 코트, 후드, 전신 바지, 근접 신발 등 모든 적절한 안전 관행과 개인 보호 장비를 사용해야 합니다.
1. 이중 카복실 폴리에틸렌 ?...

<ol>
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1H NMR스펙트럼(도 2)은CT-PEG 중합체 및 PEI-g-PEG 중합체의 성공적인 합성을 확인합니다. PEG와 PEI의 분자량은 각각 1,000및 1,200이었습니다. 또한, EDC/NHS 촉매 시스템은 아미드 반응을 통해 PEI-g-PEG 합합체를 합성하는 데 사용되었습니다. PEG와 PEI의 분자량이 PEI-g-PEG 합합체를 합성하기 위해 변경되면 반응 시간과 촉매 시스템을 재평가해야 합니다. 또한, AUNPs에 대한 PEI-g-PEG ?...

전 세계적으로 주요 공중 보건 문제이기 때문에 암은 치료율이 낮고 재발률이 높고 사망률이 높은 것으로 널리 특징지으며사망률은 1,2. 현재 종래의 항암 방법은 수술, 화학요법 및 방사선 요법3을포함하며, 그 중 화학요법은 클리닉4에서암 환자를 위한 1차 치료법이다. 임상중항암제는 주로 파클리탁셀(PTX)5 및 독소루비신(DOX)6,7을포함한다. 항신성형치료제인 DOX는 암 세포독성 및 암세포 증식 억제의 장점으로 임상화학요법에 광범위하게 적용되어왔다8,9. 그러나 DOX는 심장독성을 10,11로유발하며, DOX의 짧은 반감기는클리닉(12)에서의적용을 제한한다. 따라서, 분해가능한 약물 운반체는 DOX를 적재하고 통제된 방식으로 표적 영역으로 안전하게 방출하기 위해 필요합니다.
나노 입자는 표적 약물 전달 시스템에 널리 사용되어 왔으며 암 치료에 몇 가지 장점이 있습니다 (즉, 크기가 큰 표면 대 부피 비율, 작은 크기, 다양한 약물을 캡슐화하는 능력 및 튜닝 표면 화학 등). 13,14,15. 특히, 금 나노입자(AuNPs)는 광열암치료제(16,17)와같은 생물학적 및 생체 의학 응용 분야에서 널리 사용되고 있다. 촉진 합성 및 일반 표면 기능화와 같은 AuNPs의 독특한 특성은 암치료(18)의임상 분야에서 우수한 전망을 가지고 있다. 또한, AuNPs는 약물 전달 전략을 식별하고, 종양을 진단하고, 많은 연구에서 저항을 극복하기 위해 사용되어 왔다19,20.
하지만, AuNPs는 표적화 및 접근성 특성과 같은 향상된 투과 및 보존(EPR)을 통해 종양 병변에서 높은 국소 방출을 통해 약물 내성을 극복하기 위해 더욱 맞춤화되어야 합니다. 중합체 기능성 AuNPs는 소수성 항암제의 용용성 향상 및 장기간 순환시간(21,22)과같은 독특한 장점을 나타내었다. 폴리에틸렌 글리콜(PEG), 폴리에틸렌리민(PEI), 히알루론산, 헤파린, 크산탄껌 등 다양한 생체적합성 폴리머가 AuNP 코팅에 사용되어 왔다. 그런 다음 AuNP의 페이로드뿐만 아니라 안정성이 잘향상됩니다(23). 구체적으로, PEI는 1차, 이차 및 고등아민(24)의많은 반복 단위로 구성된 고도로 분진된 중합체이다. PEI는 우수한 용해도, 낮은 점도 및 높은 수준의 기능을 가지고 있으며, 이는 AuNPs코팅에 적합합니다.
한편, 항암제는 하중 효율이 향상되어 암세포에 직접 전달되어야 하며, 1차 및 첨단 전이성 종양 을 치료하기 위한 독성이 낮을 수있다(25). 표적 리간드항은 항암제 표적 전달시스템(26)에큰 잠재력을 가지고 있다. 표적 분자 결합에 대한 선택성은 특이성을 표적으로 하는 항암제를 부여하고 병성 조직에 있는 약 농축을 증가합니다(27). 더 많은 리간드는 항체, 폴리펩티드 및 소분자를 포함한다. 다른 리간드에 비해, 핵산 aptamers는 체외에서 합성될 수 있고 수정하기 쉽습니다. AS1411은 암세포28,29,30에과발현 표적 핵단백질 수용체에 구체적으로 결합하기 위해 안정된 조광 G-테트라머 구조를 형성하는 수정되지 않은 26bp 인포디스터 올리고뉴클레오티드이다. AS1411은 많은 암세포의 증식을 억제하지만 건강한세포(31,32)의성장에영향을 미치지 않는다. 그 결과, AS1411은 이상적인 표적 약물 전달 시스템을 제조하는 데 사용되어 왔다.
본 연구에서는, PEI-g-PEG 공중합체는 아마이드 반응을 통해 합성되고, PEI-g-PEG 공합체 코팅된 금 나노입자(PEI-g-PEG@AuNPs)가 제조된다. 또한 DOX 및 AS1411은 도 1에도시된 바와 같이 준비된 PEI-g-PEG@AuNPs 순차적으로 연결된다. 이 상세한 프로토콜은 연구원이 DOX 및 AS1411로로드된 새로운 PEI-g-PEG@AuNPs 제조와 관련된 많은 일반적인 함정을 피할 수 있도록 돕기 위한 것입니다.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>4-Dimethylaminopyridine</td>
			<td>Macklin</td>
			<td>D807273</td>
			<td></td>
		</tr>
		<tr>
			<td>A549 cell</td>
			<td></td>
			<td>ATCC CCL-185TM</td>
			<td></td>
		</tr>
		<tr>
			<td>AS1411</td>
			<td>BBI Life Sciences Corporation</td>
			<td></td>
			<td>5&#39;-d (TTTGGTGGTGGTGGTTGTGGTGGTGGTGG) FL-AS1411 (fluorophore-labeled AS1411)</td>
		</tr>
		<tr>
			<td>Anhydrous Tetrahydrofuran (THF)</td>
			<td>SinoPharm Chemical Reagent Co., Ltd</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Cell counting kit-8 (CCK-8)</td>
			<td>Sigma Aldrich</td>
			<td>96992-500TESTS-F</td>
			<td></td>
		</tr>
		<tr>
			<td>Dichloromethane</td>
			<td>Traditional Chinese medicine</td>
			<td>80047318</td>
			<td></td>
		</tr>
		<tr>
			<td>Diethyl ether (Et2O)</td>
			<td>SinoPharm Chemical Reagent Co., Ltd</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Dimethyl sulfoxide</td>
			<td>Macklin</td>
			<td>D806645</td>
			<td></td>
		</tr>
		<tr>
			<td>Dulbecco&#39;s modified Eagle&#39;s medium (DMEM)</td>
			<td>Sigma Aldrich</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Doxorubicin hydrochloride</td>
			<td>Rhawn</td>
			<td>R017518</td>
			<td></td>
		</tr>
		<tr>
			<td>Ether absolute</td>
			<td>Traditional Chinese medicine</td>
			<td>80059618</td>
			<td></td>
		</tr>
		<tr>
			<td>Field Emission Transmission Electron Microscope</td>
			<td>FEI Company</td>
			<td>Tecnai G2 F 20</td>
			<td></td>
		</tr>
		<tr>
			<td>Gold(III) chloride trihydrate</td>
			<td>Rhawn</td>
			<td>R016035</td>
			<td></td>
		</tr>
		<tr>
			<td>Laser Particle-size Instrument</td>
			<td>Malvern Instruments Ltd</td>
			<td>ZetasizerNanoZS/Masterszer3000E</td>
			<td></td>
		</tr>
		<tr>
			<td>Microplate Reader</td>
			<td>Molecular Devices</td>
			<td>SpectraMax 190</td>
			<td></td>
		</tr>
		<tr>
			<td>N-(3-Dimethylaminopropyl)-N&#39;-ethylcarbodiimide hydrochloride</td>
			<td>Macklin</td>
			<td>N808856</td>
			<td></td>
		</tr>
		<tr>
			<td>N-Hydroxysuccinimide</td>
			<td>Macklin</td>
			<td>H6231</td>
			<td></td>
		</tr>
		<tr>
			<td>NMR software</td>
			<td>Delta 5.2.1</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Nuclear Magnetic Resonance Spectrometer</td>
			<td>JEOL</td>
			<td>JNM-ECZ600R/S3</td>
			<td></td>
		</tr>
		<tr>
			<td>Origin 8.5</td>
			<td>OriginLab</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Penicillin</td>
			<td>Sigma Aldrich</td>
			<td>V900929-100ML</td>
			<td></td>
		</tr>
		<tr>
			<td>Phosphate-buffered saline</td>
			<td>Sigma Aldrich</td>
			<td>P4417-100TAB</td>
			<td></td>
		</tr>
		<tr>
			<td>Poly(ethylene glycol)</td>
			<td>Sigma Aldrich</td>
			<td>81188</td>
			<td>BioUltra, average Mn ~ 1000</td>
		</tr>
		<tr>
			<td>Poly (ethyleneimine) solution</td>
			<td>Sigma Aldrich</td>
			<td>482595</td>
			<td>average Mn ~ 1200, 50 wt.% in H2O</td>
		</tr>
		<tr>
			<td>Sodium borohydride, powder</td>
			<td>Acros</td>
			<td>C18930</td>
			<td></td>
		</tr>
		<tr>
			<td>Streptomycin</td>
			<td>Sigma Aldrich</td>
			<td>85886-10ML</td>
			<td></td>
		</tr>
		<tr>
			<td>Succinic anhydride</td>
			<td>Traditional Chinese medicine</td>
			<td>30171826</td>
			<td></td>
		</tr>
		<tr>
			<td>Tetrahydrofuran</td>
			<td>Traditional Chinese medicine</td>
			<td>40058161</td>
			<td></td>
		</tr>
		<tr>
			<td>Triethylamine</td>
			<td>Traditional Chinese medicine</td>
			<td>80134318</td>
			<td></td>
		</tr>
		<tr>
			<td>UV/VIS/NIR Spectrometer</td>
			<td>Lambda950</td>
			<td>Lambda950</td>
			<td></td>
		</tr>
		<tr>
			<td>X-ray Photoelectron Spectrometer</td>
			<td>Thermo&#8194;Fisher&#8194;Scientific</td>
			<td>K-ALPHA 0.5EV</td>
			<td></td>
		</tr>
	</tbody>
</table>

synthesis of aptamer-pei-g-peg modified gold nanoparticles loaded with doxorubicin for targeted drug delivery

건강한 세포에서 약물 내성 및 독성으로 인해 독소루비신(DOX)의 사용은 임상 암 요법에서 제한적입니다. 이 프로토콜은 아미드 반응을 통해 로드된 aptamer(AS1411) 및 DOX를 탑재한 폴리에틸렌 글리콜(PEI-g-PEG) 중합체 기능성 금 나노입자(AuNPs)로 이식된 폴리(에틸레니민)의 설계를 설명한다. AS1411은 특히 DOX가 건강한 세포 대신 암세포를 표적으로 할 수 있도록 암세포에 표적 뉴클레놀린 수용체와 결합된다. 첫째, PEG는 카박스화되어 1HNMR 분석에 의해 확인된 PEI-g-PEG 중합체를 얻기 위해 분기된 PEI에 이식된다. 다음으로, PEI-g-PEG 공합체 코팅 금 나노입자(PEI-g-PEG@AuNPs)가 합성되고, DOX 및 AS1411은 아마드 반응을 통해 점차적으로 AuNPs에 공유결합된다. 준비된 AS1411-g-DOX-g-PEI-g-PEG@AuNPs 의 직경은 ~39.9nm이며, 제타 전위 -29.3mV로, 나노입자가 물과 세포 배지에서 안정되어 있음을 나타낸다. 세포 세포 독성 연구는 새로 설계된 DOX로드 AuNPs가 암세포 (A549)를 죽일 수 있음을 보여줍니다. 이 합성은 순차적 인 아미데 반응에 의해 달성되는 AuNPs에 PEI-g-PEG 공중 합합체, aptamers 및 DOX의 섬세한 배열을 보여줍니다. 이러한 aptamer-PEI-g-PEG 기능화된 AuNPs는 암 치료에서 표적 약물 전달을 위한 유망한 플랫폼을 제공합니다.

1 H NMR 분광법은 CT-PEG 중합체 및 PEI-g-PEG 중합체(도2)의성공적인 합성을 확인하기 위해 사용되었다. 도 2a는 δ = 3.61 ppm 및 carboxyl 양성자 신호에서 메틸렌 양성자 신호가 δ = 2.57 ppm에서 CT-PEG 폴리머의 성공적인 합성을 확인함을 나타낸다. 도 2b는 δ = 2.6 ppm 및 peI의 양성자 신호에서 PEG의 메틸렌 양?...

Watch this Scientific Journal Video about Synthesis of Aptamer-PEI-g-PEG Modified Gold Nanoparticles Loaded with Doxorubicin for Targeted Drug Delivery at JoVE.com

Synthesis of Aptamer-PEI-g-PEG Modified Gold Nanoparticles Loaded with Doxorubicin for Targeted Drug Delivery

이 프로토콜에서, 독소루비신로드 AS1411-g-PEI-g-PEG 변형 금 나노 입자는 3 단계 아마이드 반응을 통해 합성된다. 이어서, 독소루비신은 암 치료를 위한 암세포를 표적으로 하기 위하여 장전되고 전달된다.

표적 약물 전달을 위해 독소루비신으로 로드된 압타머-PEI-g-PEG 수정 금 나노 입자의 합성

Due to drug resistance and toxicity in healthy cells, use of doxorubicin (DOX) has been limited in clinical cancer therapy. This protocol describes the ...

Research

JoVE Journal

Chemistry

Template Directed Synthesis of Plasmonic Gold Nanotubes with Tunable IR Absorbance

템플릿 조정할 IR의 흡광도와 Plasmonic 골드 나노 튜브의 합성을 감독

A nearly parallel array of pores can be produced by anodizing aluminum foils in acidic environments1, 2. Applications of anodic aluminum oxide (AAO) ...

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Preparation and Characterization of SDF-1ÃƒÅ½Ã‚Â±-Chitosan-Dextran Sulfate Nanoparticles

SDF-1α-키토산 덱스 트란 황산 나노 입자의 제조 및 특성

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A Simple Method for the Size Controlled Synthesis of Stable Oligomeric Clusters of Gold Nanoparticles under Ambient Conditions

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Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of ...

Hydroquinone Based Synthesis of Gold Nanorods

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Chemical Precipitation Method for the Synthesis of Nb2O5 Modified Bulk Nickel Catalysts with High Specific Surface Area

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We demonstrate a method for the synthesis of NixNb1-xO catalysts with sponge-like and fold-like nanostructures. By varying the Nb:Ni ratio, a series of ...

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Rapid Nanoprobe Signal Enhancement by In Situ Gold Nanoparticle Synthesis

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