江兵兵，宋瓊芳，陳明，陳學(xué)琴

(1.湖北大學(xué)材料科學(xué)與工程學(xué)院，湖北 武漢 430062；2.有機(jī)化工新材料湖北省協(xié)同創(chuàng)新中心(湖北大學(xué))，湖北 武漢430062)

層層自組裝功能化涂層及其生物應(yīng)用研究進(jìn)展

江兵兵1，2，宋瓊芳1，陳明1，陳學(xué)琴1

(1.湖北大學(xué)材料科學(xué)與工程學(xué)院，湖北 武漢 430062；
2.有機(jī)化工新材料湖北省協(xié)同創(chuàng)新中心(湖北大學(xué))，湖北 武漢430062)

層層自組裝作為一種新穎的材料制備技術(shù)，具有制備條件可控，適用于多種物質(zhì)，具備產(chǎn)業(yè)化前景等諸多優(yōu)點(diǎn).探討層層自組裝技術(shù)的優(yōu)勢(shì)及其近幾年的生物醫(yī)學(xué)應(yīng)用(構(gòu)建生物相容性界面，改性組織工程支架表面，藥物載體的制備)和功能化涂層應(yīng)用，重點(diǎn)詳述用層層自組裝技術(shù)制備功能化涂層并使其具有不同響應(yīng)性的研究進(jìn)展.

層層自組裝技術(shù)；功能化涂層；響應(yīng)性；應(yīng)用

0 引言

現(xiàn)代醫(yī)學(xué)的進(jìn)步與生物材料的發(fā)展密不可分.從外科整形、心血管植入支架，到人體骨科置換和修復(fù)、生物組織工程，再到藥物傳遞系統(tǒng)，醫(yī)用生物材料遍及生物醫(yī)學(xué)的各個(gè)領(lǐng)域[1].

層層自組裝技術(shù)，作為一種新穎的制備納米膜的技術(shù)，由德國(guó)科學(xué)家Decher、Hong等在 1991年正式提出[2-3]，并于1997年將詳細(xì)技術(shù)首次發(fā)表于《Science》[4]，在過(guò)去的20多年內(nèi)得到了迅猛的發(fā)展.經(jīng)典的層層自組裝驅(qū)動(dòng)力是靜電作用力[5-6]，除此之外，氫鍵[7-8]、疏水[9-10]、共價(jià)鍵[11-12]、主客體[13-14]、電荷轉(zhuǎn)移[15]等作用力同樣可以用類似的原理形成交替的多層膜.張希課題組[16]和Rubner課題組[17]在1997年幾乎同時(shí)提出以氫鍵作為驅(qū)動(dòng)力形成多層膜；Crooks課題組[18]也在1997年提出了以共價(jià)鍵為驅(qū)動(dòng)力構(gòu)建薄膜.

層層自組裝技術(shù)擁有其獨(dú)特的優(yōu)勢(shì)，如表1所示.該類多層膜的物理、化學(xué)性質(zhì)可以很容易通過(guò)改變自組裝多層膜的層數(shù)以及聚電解質(zhì)的種類進(jìn)行調(diào)控.這些特點(diǎn)極大擴(kuò)展了層層自組裝多層膜的應(yīng)用范圍，使得層層自組裝技術(shù)成為了醫(yī)學(xué)材料中構(gòu)筑復(fù)合功能性薄膜和藥物載體不可或缺的方法.由此可見(jiàn)，層層自組裝技術(shù)在21世紀(jì)初便得到廣泛應(yīng)用也便不無(wú)道理.

表1 層層自組裝的優(yōu)勢(shì)

1 層層自組裝的生物醫(yī)學(xué)應(yīng)用

1.1構(gòu)建生物相容性界面層層自組裝技術(shù)基于表1中的種種優(yōu)勢(shì)而被廣泛用于構(gòu)建生物相容性界面，減小生物材料和人體的排斥反應(yīng)，使細(xì)胞能更好地附著在材料表面并進(jìn)行增殖.譚琦[40]等用層層自組裝技術(shù)使肝素和殼聚糖在去細(xì)胞質(zhì)基質(zhì)表面進(jìn)行層層自組裝，并進(jìn)行化學(xué)交聯(lián).結(jié)果顯示，其生物力學(xué)性能和生物相容性明顯優(yōu)于單純?nèi)ゼ?xì)胞質(zhì)基質(zhì)，該層層自組裝材料具備良好的內(nèi)皮細(xì)胞粘附能力及增殖能力.Wu等[41]將肝素和氧化石墨烯通過(guò)靜電作用自組裝于納米纖維表面.結(jié)果表明用該復(fù)合膜改性后的納米纖維其親水性得到改善，細(xì)胞粘附性能更好，還在一定程度上抑制了炎癥的產(chǎn)生.余森等[42]通過(guò)層層自組在靜電層層自組裝在TiO2薄膜表面引入肝素-白蛋白多層復(fù)合膜.結(jié)果表明，經(jīng)表面肝素-白蛋白復(fù)合涂層修飾處理后，其表面更為光滑、平整，同時(shí)材料表面的溶血率顯著降低，試樣表面無(wú)凝血塊出現(xiàn)，且粘附的少量血小板，激活反應(yīng)輕微，且材料的抗凝血性能和血液相容性均得到了明顯的改善.

上述結(jié)果均表明，用層層自組裝技術(shù)構(gòu)建生物相容性界面之后，材料本身的性能沒(méi)有降低，還能緩解人體對(duì)材料的免疫反應(yīng)，和材料起協(xié)同作用，在生物體內(nèi)發(fā)揮更好的作用.

1.2組織工程支架表面改性層層自組裝技術(shù)同樣被用于組織工程支架領(lǐng)域.經(jīng)多層膜改性的組織工程支架可為細(xì)胞和組織生長(zhǎng)提供更為適宜的環(huán)境，利于激活細(xì)胞特異的基因表達(dá).用于研究組織工程結(jié)構(gòu)的材料需要具備良好的生物相容性和降解性，因此大多我們選取天然聚電解質(zhì)之類的材料.沈家驄等[43]將靜電層層自組裝的技術(shù)引入制備好的聚乳酸(PLLA)多孔支架材料中.成功地在支架上制備出硫磺軟骨素/膠原(CS/COL)多層膜.與未改性的PLLA相比，經(jīng)多層膜改性的PLLA材料表面細(xì)胞的黏附率、增殖率和活性都得到了顯著的改善，細(xì)胞邊緣清晰完整，尺寸正常，而且細(xì)胞分布均勻，細(xì)胞密度大，基本鋪滿培養(yǎng)板基底.Matthew等[44]以氧化鋅(ZnO)納米粒子和聚苯乙烯磺酸鈉(PSS)為組裝基元制備了多層膜.該多層膜能在一定程度上防止細(xì)菌感染.

1.3微膠囊型藥物載體層層組裝所形成的功能化涂層應(yīng)用廣泛，主要應(yīng)用于藥物的載入和釋放.其載藥方式可分為前載藥[45]和后載藥[46-47]兩種：(1)前載藥即在裝載的過(guò)程中進(jìn)行載藥[48]；(2)后載藥即通過(guò)后處理的方式進(jìn)行載藥：已制備好的多層膜體系，浸入含有藥物分子的溶液中進(jìn)行載藥，通過(guò)分子間的識(shí)別和物理吸附的方法包埋藥物，較前一種方法載藥量較低，但該種載藥方式能保持較高的藥物活性.李峻柏等[49]則利用N-異丙基丙烯酰胺(PNIPAAm)和Alg之間的氫鍵作用制備了層層自組裝微膠囊.當(dāng)溫度高于PNIPAAm的低臨界溶解溫度(LCST)時(shí)，PNIPAAm由親水物質(zhì)轉(zhuǎn)變成疏水性物質(zhì)，導(dǎo)致了分子鏈緊的收縮，繼而改變囊壁的通透性.通過(guò)改變溫度，可以很好的控制藥物的包裹和釋放.Sukhorukov等[50]合成了一種帶負(fù)電的側(cè)鏈為偶氮苯的聚合物(PAzo)，通過(guò)與PAH 和聚磺酸基乙烯(PVS)進(jìn)行層層自組裝制備出(PAH/PAzo)3PAH/PV S 微膠囊藥物載體.這種微膠囊在不同光照的情況下會(huì)因?yàn)榕嫉綐?gòu)象的變化而發(fā)生體積和膜滲透性的可逆變化，從而可以實(shí)現(xiàn)藥物控釋.

2 功能化涂層及其響應(yīng)性

2.1功能化涂層以薄膜基材制備功能型多層膜，由于其豐富的組裝基元、優(yōu)越的薄膜調(diào)控功能，被廣泛研究和應(yīng)用.我們[51]使用聚賴氨酸(PLL)和聚(L-谷氨酸)(PLGA)制備聚多肽多層膜，并在膜中引入了IL-12細(xì)胞因子，從而自發(fā)激活人體免疫系統(tǒng)進(jìn)行殺菌，該方法不僅可以有效地避免醫(yī)療器械植入所引起的感染同時(shí)也不會(huì)產(chǎn)生耐藥性問(wèn)題.我們[52]還采用不同聚電解質(zhì)修飾的碳酸鈣膠體微粒為載體與多肽材料進(jìn)行組裝.研究表明，在37 ℃，pH=7.4條件下，釋放周期長(zhǎng)達(dá)數(shù)周.該方法大大提高了藥物的活性，為多層膜的藥物負(fù)載提供了廣闊的設(shè)計(jì)空間.Saibom等[53]首先將不帶電的聚乙二醇-聚乳酸共乙醇酸(PEG-PLG)膠束為載體與聚電解質(zhì)透明質(zhì)酸(HA)進(jìn)行混合，隨后與聚電解質(zhì)LPEI進(jìn)行交替層層組裝.結(jié)果顯示，HA多層膜具有良好的生物相容性；而載有紫杉醇(PTX)藥物的多層膜在對(duì)人平滑肌細(xì)胞的抗粘附測(cè)試則表明，PTX的緩釋可以通過(guò)改變組裝的層數(shù)達(dá)到理想效果，當(dāng)組裝層數(shù)為20層時(shí)，PTX釋放周期長(zhǎng)達(dá)14 d，對(duì)防止手術(shù)后的再感染具有重要的意義.

在過(guò)去的研究發(fā)展歷程中，不僅實(shí)現(xiàn)了疏水的有機(jī)小分子等非水溶性物質(zhì)的層層組裝膜的構(gòu)筑，也成功地在同一體系中負(fù)載多種不同藥物，通過(guò)材料對(duì)某些特定信號(hào)或者生物體內(nèi)某種特定信號(hào)的響應(yīng)[54].根據(jù)材料的性質(zhì)，選取不同的材料可以達(dá)到不同的響應(yīng)效果.同時(shí)，在外界條件刺激下，智能型多層膜能夠?qū)崿F(xiàn)物質(zhì)的選擇性包埋，并對(duì)藥物進(jìn)行智能化控釋.這樣既可以減少藥物在人體內(nèi)的毒性作用，也可以維持藥物濃度在有效治療濃度范圍內(nèi)，延長(zhǎng)其在體內(nèi)/體外的作用時(shí)間.根據(jù)釋放機(jī)制的不同可以將這些響應(yīng)手段分為物理和化學(xué)兩大類.物理手段主要包括溫度[27]、光[29-30]、磁場(chǎng)[31-32]和超聲變化[33-34]等使層層組裝體系解離釋放藥物，而化學(xué)方法主要包括pH[35-37]和酶[38-39]等.

2.2溫敏性響應(yīng)溫度響應(yīng)是用來(lái)控釋藥物的常見(jiàn)手段之一.自組裝體系具有了溫敏響應(yīng)性后，多層膜在各研究領(lǐng)域有更廣泛的應(yīng)用.其中，最為常見(jiàn)的溫度敏感型高分子材料N-異丙基丙烯酰胺(PNIPAAm).PNIPAAm被廣泛引入層層自組裝體系，既適用于微膠囊體系，又可以作為組成薄膜的片段.除了上文所述的微膠囊體系，PNIPAAm還能組裝為溫敏響應(yīng)的功能性薄膜，Quinn等[55]率先將PNIPAAm與聚丙烯酸(PAA)通過(guò)氫鍵作用結(jié)合成多層膜并負(fù)載染料進(jìn)行測(cè)試，實(shí)驗(yàn)表明通過(guò)對(duì)溫度的調(diào)節(jié)可以控制染料的裝載和釋放.除了PNIPAAm外，Vincent等[56]以溫敏型陽(yáng)離子嵌段聚合物和光敏染料為原料，用層層自組裝技術(shù)制備了多層膜.(2-二甲基氨基)甲基丙烯酸乙酯嵌段共聚2-(乙二醇)甲基醚甲基丙烯酸酯(PDMAEMA59-b-PDEGMA318, PDD)表現(xiàn)出明顯的溫度依賴性，在26 ℃時(shí)PDD/PSS的雙層膜厚度約為(2.65±0.02) nm，而31 ℃則僅為(1.34±0.02) nm，使之成為傳感裝置中極有潛力的溫敏材料.

2.3光敏響應(yīng)用光為刺激手段進(jìn)行智能化控制是一種比較溫和的手段.光敏物質(zhì)使多層膜增加了孔結(jié)構(gòu)，與無(wú)孔的多層膜相比，其比表面積更大，通透性更好，應(yīng)用更多元化.以卟啉為例，卟啉是一種被廣泛應(yīng)用于醫(yī)療和其他領(lǐng)域的光敏劑，在光照下可以激發(fā)出具有強(qiáng)氧化力的活性氧自由基(ROS).光照下卟啉產(chǎn)生的具有強(qiáng)氧化能力的活性氧自由基能夠解離兩種成膜聚合物的分子鏈，從而使多層膜變成多孔結(jié)構(gòu)，增加薄膜通透性.Volodkin等[57]報(bào)道一種由HA與PLL作為聚電解質(zhì)，并負(fù)載了金納米粒子的多層薄膜.薄膜中的金納米粒子在近紅外照射下變得活躍，經(jīng)表征顯示薄膜局部的溫度上升，該現(xiàn)象主要是因?yàn)楣饽苻D(zhuǎn)化成熱能.李草[58]分別選用了兩種具有良好生物相容性的材料，卟啉封端的聚賴氨酸(APP-PLL)以及鯡魚精DNA作為聚陽(yáng)離子和聚陰離子進(jìn)行層層自組裝，薄膜通過(guò)控制光照時(shí)間來(lái)控制多孔膜上孔洞的數(shù)量和大小.

2.4pH響應(yīng)pH響應(yīng)的物質(zhì)能調(diào)控多層膜的結(jié)構(gòu)，使其在不同的pH下呈現(xiàn)不同的特性，以達(dá)到某些特定的效果.參與靜電層層組裝的膜材料很多是弱聚電解質(zhì)，這類層層組裝體系具有pH敏感性的特性，如聚陽(yáng)離子材料聚烯丙胺鹽酸鹽(PAH) 就是一種弱電解質(zhì)(pKa=8.7)聚多堿材料.對(duì)于這種聚多堿膜材料組裝得到的多層膜，當(dāng)外環(huán)境的pH 值高于它們的pKa時(shí)，多層膜就會(huì)發(fā)生解離.同樣的對(duì)于聚多酸弱電解質(zhì)膜材料組裝得到的多層膜體系，當(dāng)外環(huán)境的pH值低于它們的pKa時(shí)，聚電解質(zhì)質(zhì)子化使多層膜解離.

Kainourgios等[59]制備了pH敏感型聚電解質(zhì)多層膜微球.該微球由聚二甲基二烯丙基氯化銨/聚苯乙烯磺酸鈉(PDADMAC/PSS)多層膜和交聯(lián)聚乙二醇組成，并在微球中載入DNR，于不同的pH值下測(cè)定其釋放行為.結(jié)果顯示，在pH值為4時(shí)，啟釋放量?jī)H為15%，而在pH值為7.4的環(huán)境下，DNR呈爆發(fā)性釋放，一小時(shí)內(nèi)其釋放量約為65%.此特性使該微球載體能應(yīng)用于一定的pH環(huán)境.

2.5其他響應(yīng)方式除卻上述響應(yīng)方式，磁性響應(yīng)，酶響應(yīng)等響應(yīng)手段也有一定的研究進(jìn)展.Wang等[60]用層層自組裝技術(shù)在Fe3O4@SiO2納米微球表面包裹聚烯丙基胺-葡聚糖微凝膠，形成復(fù)合微球并用來(lái)負(fù)載布洛芬.結(jié)果顯示，該載體能在0.9%的NaCl溶液中持續(xù)釋放藥物，微球外層的交聯(lián)膜有很好的溶脹能力，而且其表面有大量質(zhì)子化氨基團(tuán)，能使該復(fù)合載體有很好的.Baumert等[61]則將帶負(fù)電的si-RNA與帶正電的PEI進(jìn)行復(fù)合，形成正電復(fù)合體PEI-siRNA、并同HA、CHI進(jìn)行層層自組裝，制備出對(duì)丙型肝炎病毒有很好抑制作用的多層膜.該薄膜通過(guò)細(xì)胞透明質(zhì)酸酶對(duì)薄膜裂解的作用，siRNA不斷被釋放出來(lái)，達(dá)到治療的效果.

層層自組裝的功能化涂層，由于組裝物質(zhì)的多元化，其功能也不盡相同，應(yīng)用廣泛.隨著科學(xué)技術(shù)的發(fā)展，層層自組裝多層膜會(huì)有更多不同種類的功能.

3 展望

層層自組裝是基于物質(zhì)間的相互作用力的，通過(guò)物質(zhì)的交替沉積而形成納米結(jié)構(gòu)的多層膜一種手段.這種新型技術(shù)涉及物理、化學(xué)、生命科學(xué)和材料科學(xué)、藥理學(xué)和工程學(xué)等方面知識(shí)，在各研究領(lǐng)域中扮演著重要的角色.從不可降解性物質(zhì)，發(fā)展到可降解，繼而多功能性選擇，層層自組裝取得了跨越式發(fā)展，從無(wú)機(jī)相到有機(jī)相，浸涂到噴涂，技術(shù)也在不斷的成熟.通過(guò)設(shè)計(jì)負(fù)載多種藥物的功能性薄膜并在不同的環(huán)境下進(jìn)行響應(yīng)控釋，仍是當(dāng)前及以后的研究熱點(diǎn).層層自組裝在基礎(chǔ)性研究中取得突破性進(jìn)展的同時(shí)，將基礎(chǔ)性研究的成果逐步進(jìn)行體內(nèi)/外效果測(cè)試、評(píng)價(jià)，并運(yùn)用于臨床，其研究與開發(fā)對(duì)拓展高性能生物醫(yī)用材料具有重要的理論意義和現(xiàn)實(shí)價(jià)值.

[1] 高長(zhǎng)有. 醫(yī)用高分子材料[M]. 北京：化學(xué)工業(yè)出版社, 2006.

[2] Decher G, Hong J D. Buildup of ultrathin multilayer films by a self-assembly process, 1 consecutive adsorption of anionic and cationic bipolar amphiphiles on charged surfaces[J].Makromolekulare Chemie Macromolecular Symposia,1991, 46(1):321-327.

[3] Decher G, Hong J D, Schmitt J, et al. Buildup of ultrathin multilayer films by a self-assembly process(III):consecutively alternating adsorption of anionic and cationic polyelectrolytes on charged surfaces[J].Thin Solid Films,1992, 210/211(2):831-835.

[4] Decher G. Fuzzy nanoassemblies: toward layered polymeric multicomposites[J]. Science, 1997, 277(5330):1232-1237.

[5] 徐揚(yáng)子, 張候. CdS包覆SiO2核/殼和空腔結(jié)構(gòu)納米球制備及發(fā)光性能[J].湖北大學(xué)學(xué)報(bào)(自然科學(xué)版), 2015(3):257-261.

[6] Velk Natalia, Uhlig Katja, Vikulina Anna,et al. Mobility of lysozyme in poly(l-lysine)/hyaluronic acid multilayer films[J]. Colloids and Surfaces B:Biointerfaces, 2016(1):343-350.

[7] Eugenia K, Veronika K, Sukhishvili S A. Layer‐by‐layer hydrogen‐bonded polymer films: from fundamentals to applications[J]. Advanced Materials, 2009, 21(21):3053-3065.

[8] Yu C, Wei H. Synthesis and characterization of glucocorticoid functionalized poly(N-vinyl pyrrolidone): a versatile prodrug for neural interface[J]. Biomacromolecules, 2010, 11(5):1298-1307.

[9] Xu L, Zhu Z, Sukhishvili S A. Polyelectrolyte multilayers of diblock copolymer micelles with temperature-responsive cores.[J]. Langmuir, 2011, 27(1):409-415.

[10] Alhariri L A, Reisch A, Schlenoff J B. Exploring the heteroatom effect on polyelectrolyte multilayer assembly: the neglected polyoniums[J]. Langmuir, 2011, 27(7):3914-3919.

[11] Hu X, Ji J. Covalent layer-by-layer assembly of hyperbranched polyether and polyethyleneimine: multilayer films providing possibilities for surface functionalization and local drug delivery[J]. Biomacromolecules, 2011, 12(12):4264-71.

[12] Such G K, Quinn J F, Quinn A, et al. Assembly of ultrathin polymer multilayer films by click chemistry[J]. Journal of the American Chemical Society, 2006, 128(29):9318-9319.

[13] Suzuki I, Egawa Y, Mizukawa Y, et al. Construction of positively-charged layered assemblies assisted by cyclodextrin complexation[J]. Chemical Communications, 2002, 13(2):164-165.

[14] Crespobiel O, Dordi B, Reinhoudt D N, et al. Supramolecular layer-by-layer assembly: alternating adsorptions of guest-and host-functionalized molecules and particles using multivalent supramolecular interactions[J]. Journal of the American Chemical Society, 2005, 127(20):7594-7600.

[15] Wang F, Ma N, Chen Q， et al.Halogen bonding as a new driving force for layer-by-layer assembly[J]. Langmuir, 2007,23(19): 9540-9542.

[16] Wang L, Wang Z, Zhang X, et al. A new approach for the fabrication of an alternating multilayer film of poly(4-vinylpyridine) and poly(acrylic acid) based on hydrogen bonding[J].Macromolecular Rapid Communications,1997,18(6):509-514.

[17] Vainas T, Stassen F R M, Bruggeman C A, et al.Molecular-Level processing of conjugated polymers. 4. layer-by-layer manipulation of polyaniline via hydrogen-bonding interactions[J]. Macromolecules, 1997, 30(9):2717-2725.

[18] Liu Y, Bruening M L, Bergbreiter D E, et al. Multilayer dendrimer-polyanhydride composite films on glass, silicon, and gold wafers[J]. Angewandte Chemie International Edition, 1997, 36(19):2114-2116.

[19] Jiang X, Chen Z, LV D, et al. Basic law controlling the growth regime of layer-by-layer assembled polyelectrolyte multilayers[J]. Macromolecular Chemistry & Physics, 2007, 209(2):175-183.

[20] Paterno L G, Constantino C J L, Oliveira O N, et al. Self-assembled films of poly(o-ethoxyaniline) complexed with sulfonated lignin[J]. Colloids & Surfaces B:Biointerfaces, 2002, 23(4):257-262.

[21] Chandrawati R, Koeverden M P V, Lomas H, et al. Multicompartment particle assemblies for bioinspired encapsulated reactions[J]. Journal of Physical Chemistry Letters, 2011, 2(20):2639-2649.

[22] Hou S, Harrell C C, Trofin L, et al. Layer-by-layer nanotube template synthesis[J]. Journal of the American Chemical Society, 2004, 126(18):5674-5675.

[23] Liao L, Lin Y C, Bao M, et al. High-speed graphene transistors with a self-aligned nanowire gate[J]. Nature, 2010, 467(7313):305-308.

[24] Zhao W, Tong B, Shi J, et al. Fabrication and optoelectronic properties of novel films based on functionalized multiwalled carbon nanotubes and (Phthalocyaninato)Ruthenium(II) via coordination bonded layer-by-layer self-assembly[J]. Langmuir, 2010, 26(20):16084-16089.

[25] Dorokhin D, Hsu S H, Tomczak N, et al. Fabrication and luminescence of designer surface patterns withβ-cyclodextrin functionalized quantum dots via multivalent supramolecular coupling[J]. Acs Nano, 2010, 4(1):137-142.

[26] Swiston A J, Cheng C, Um S H, et al. Surface functionalization of living cells with multilayer patches[J]. Nano Letters, 2009, 8(12):4446-4453.

[27] Kim B S, Park S W, Hammond P T. Hydrogen-bonding layer-by-layer-assembled biodegradable polymeric micelles as drug delivery vehicles from surfaces[J]. Acs Nano, 2008, 2(2):386-392.

[28] Such G K, Quinn J F, Quinn A, et al. Assembly of ultrathin polymer multilayer films by click chemistry[J]. Journal of the American Chemical Society, 2006, 128(29):9318-9319.

[29] Volodkin D V, Madaboosi N ,Blacklock J, et al. Surface-supported multilayers decorated with bio-active material aimed at light-triggered drug delivery?[J]. Langmuir, 2009, 25(24):14037-14043.

[30] Liu J, Zhang Y, Wang C, et al. Magnetically sensitive alginate-templated polyelectrolyte multilayer microcapsules for controlled release of doxorubicin[J].The Journal of Physical Chemistry C,2010, 114(17):7673-7679.

[31] Liu J, Zhang Y, Wang C, et al. Magnetically sensitive alginate-templated polyelectrolyte multilayer microcapsules for controlled release of doxorubicin[J].The Journal of Physical Chemistry C, 2010, 114(17):7673-7679.

[32] Katagiri K, Nakamura M, Koumoto K. Magnet responsive smart capsules formed with polyelectrolytes, lipid bilayers and magnetic nanoparticles[J]. ACS Applied Materials & Interfaces, 2010, 2(3):768-773.

[33] Song W, He Q, Mchwald H,et al. Smart polyelectrolyte microcapsules as carriers for water-soluble small molecular drug[J]. Journal of Controlled Release, 2009, 139(2):160-166.

[34] Shchukin D G, Gorin D A, Mchwald H. Ultrasonically induced opening of polyelectrolyte microcontainers[J]. Langmuir, 2006, 22(17):7400-7404.

[35] Jiang B, Li B. Tunable drug loading and release from polypeptide multilayer nanofilms[J]. International Journal of nanomedicine, 2009, 4:37.

[36] Kim B S, Park S W, Hammond P T. Hydrogen-bonding layer-by-layer-assembled biodegradable polymeric micelles as drug delivery vehicles from surfaces[J]. Acs Nano, 2008, 2(2):386-392.

[37] Wang B, Liu P, Jiang W, et al. Yeast cells with an artificial mineral shell: protection and modification of living cells by biomimetic mineralization[J]. Angewandte Chemie International Edition, 2008, 47(19):3560-3564

[38] Sakr O S, Borchard G.Encapsulation of enzymes in layer-by-layer structures: latest advances and applications[J]. Biomacromolecules, 2013, 14(7):2117-2135.

[39] Serizawa T, Yamaguchi M, Akashi M. Alternating bioactivity of polymeric layer-by-layer assemblies: anticoagulation vs procoagulation of human blood[J]. Biomacromolecules, 2002, 3(4):724-731.

[40] 譚琦, 劉又年, 陳萬(wàn)松, 等. 化學(xué)交聯(lián)層層自組裝結(jié)構(gòu)提高去細(xì)胞基質(zhì)生物相容性研究[C].中國(guó)功能材料及其應(yīng)用學(xué)術(shù)會(huì)議,2010.

[41] Wu K, Zhang X, Yang W, et al. Influence of layer-by-layer assembled electrospun poly (l-lactic acid) nanofiber mats on the bioactivity of endothelial cells[J]. Applied Surface Science,2016,390:838-846.

[42] 余森, 于振濤, 牛金龍, 等. 醫(yī)用鈦合金Ti-3Zr-2Sn-3M0-25Nb表面自組裝抗凝血復(fù)合涂層的構(gòu)建及其血液相容性研究[C].中國(guó)有色金屬工業(yè)協(xié)會(huì)鈦鋯鉿分會(huì)2011年會(huì), 2011.

[43] Gong Y, Zhu Y, Liu Y, et al. Layer-by-layer assembly of chondroitin sulfate and collagen on aminolyzed poly(l-lactic acid) porous scaffolds to enhance their chondrogenesis[J]. Acta Biomaterialia, 2007, 3(5):677-685.

[44] Mcguffie M J, Jin H, Bahng J H, et al. Zinc oxide nanoparticle suspensions and layer-by-layer coatings inhibit staphylococcal growth[J]. Nanomedicine Nanotechnology Biology & Medicine, 2015, 12(1):33-42.

[45] Ma N, Zhang H, Song B, et al. Polymer micelles as building blocks for layer-by-layer assembly: an approach for incorporation and controlled release of aateriInsoluble dyes[J]. Chemistry of Materials, 2005, 17(20):5065-5069.

[46] Volodkin D V, Madaboosi N, Blacklock J, et al. Surface-supported multilayers decorated with bio-active material aimed at light-triggered drug delivery[J]. Langmuir the Acs Journal of Surfaces & Colloids, 2009, 25(24):14037-14043.

[47] Liu J, Zhang Y, Wang C, et al. Magnetically sensitive alginate-templated polyelectrolyte multilayer microcapsules for controlled release of doxorubicin[J]. Journal of Physical Chemistry C, 2010, 114(17):7673-7679.

[48] Wei C, Wang A, Jie Z, et al. Layer by layer assembly of albumin nanoparticles with selective recognition of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)[J]. Journal of Colloid & Interface Science, 2015, 465(12):11-17.

[49] Wang A, Cheng T, Yue C, et al. Assembly of environmental sensitive microcapsules of PNIPAAm and alginate acid and their application in drug release[J]. Journal of Colloid & Interface Science, 2009, 332(2):271-279.

[50] Bédard M, Skirtach A G, Sukhorukov G B. Optically driven encapsulation using novel polymeric hollow shells containing an azobenzene polymer[J]. Macromolecular Rapid Communications, 2007, 28(15):1517-1521.

[51] Li B, Jiang B B, Boyce B M, et al. Multilayer polypeptide nanoscale coatings incorporating IL-12 for the prevention of biomedical device-associated infections[J]. Biomaterials, 2009, 30(13):2552-2558.

[52] Jiang B, Defusco E, Li B. Polypeptide multilayer film co-delivers oppositely-charged drug molecules in sustained manners[J]. Biomacromolecules, 2010, 11(12):3630-3637.

[53] Park S, Bhang S H, La W G, et al. Dual roles of hyaluronic acids in multilayer films capturing nanocarriers for drug-eluting coatings[J]. Biomaterials, 2012, 33(21):5468-5477.

[54] Pavlukhina S, Sukhishvili S. Polymer assemblies for controlled delivery of bioactive molecules from surfaces[J]. Advanced Drug Delivery Reviews, 2011, 63(9):822-836.

[55] Quinn J F, Caruso F. Facile tailoring of film morphology and release properties using layer-by-layer assembly of thermoresponsive materials[J]. Langmuir, 2004, 20(1):20-22.

[56] Joseph V S, Kim S, Zhang Q, et al. Multilayer films composed of a thermoresponsive cationic diblock copolymer and a photoresponsive dye[J]. Polymer, 2013, 54(18):4894-4901.

[57] Volodkin D V, Madaboosi N, Blacklock J, et al. Surface-supported multilayers decorated with bio-active material aimed at light-triggered drug delivery[J]. Langmuir the Acs Journal of Surfaces & Colloids, 2009, 25(24):14037-14043.

[58] Li C, Zhang J, Yang S, et al. Controlling the growth behaviour of multilayered films via layer-by-layer assembly with multiple interactions[J]. Physical Chemistry Chemical Physics, 2009, 11(39):8835-8840.

[59] Kainourgios P, Efthimiadou E K, Tziveleka L A, et al.Comparative study of LBL and crosslinked pH sensitive PEGylated LBL microspheres: Synthesis,characterization and biological evaluation[J]. Colloids & Surfaces B Biointerfaces, 2013, 104(3):91-98.

[60] Wang L, Liao R, Li X. Layer-by-layer deposition of luminescent polymeric microgel films on magnetic Fe3O4@SiO2, nanospheres for loading and release of ibuprofen[J]. Powder Technology, 2013, 235(2):103-109.

[61] Dimitrova M, Affolter C, Meyer F, et al. Sustained delivery of siRNAs targeting viral infection by cell-degradable multilayered polyelectrolyte films[J]. Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(42):16320-16325.

Advancedprogressoflayerbylayerself-assemblyfunctionalcoatinganditsapplicationinbiology

JIANG Bingbing1，2，SONG Qiongfang1,CHEN Ming1,CHEN Xueqin1

(1.Faculty of Materials Science and Engineering, Hubei University, Wuhan 430062, China; 2.Hubei Collaborative Innovation
Center for Advanced Organic Chemical Materials(Hubei University), Wuhan 430062,China)

As a novel material preparation technology, the layer-by-layer(LBL) technique has many advantages, such as controlled preparation conditions, suitable for a variety of material and great industrialization prospects. This paper discussed the advantages of LBL self-assembly technology as well as its biomedical applications-synthesis of biocompatible interface, surface modification tissue engineering scaffolds, preparation of drug carrier-and functional applications, focusing on progress of the functional coatings and its different response.

layer-by-layer technique；functional coatings；responsiveness ；application

2017-01-08

國(guó)家自然科學(xué)基金(51503060)和湖北省自然科學(xué)基金(2014CFB549)資助

江兵兵(1972-)，男，博士，教授；陳學(xué)琴，通信作者，講師，E-mail：51545457@qq.com

1000-2375(2017)06-0639-07

O631

A

10.3969/j.issn.1000-2375.2017.06.014

(責(zé)任編輯 胡小洋)