摘要:與傳統(tǒng)的醫(yī)學(xué)手段相比,貴金屬納米顆粒具有良好的生物相容性、穩(wěn)定性與強(qiáng)光散射等性質(zhì)并且在可見光和近紅外區(qū)域可進(jìn)行等離子吸收,因此在生物醫(yī)學(xué)領(lǐng)域迅速占據(jù)一席之地.在此基礎(chǔ)上,對(duì)貴金屬納米(Ag NPs、Au NPs與Pt NPs)及其與其他物質(zhì)(TiO2、葡萄糖氧化酶、抗體與疫苗等)的組合在生物傳感、生物成像、藥物運(yùn)輸和腫瘤治療等方面的性能進(jìn)行探討.最后,對(duì)貴金屬納米顆粒所提及的納米醫(yī)用領(lǐng)域的應(yīng)用優(yōu)勢(shì)進(jìn)行總結(jié),并指出現(xiàn)存問題和對(duì)未來的期望.
關(guān)鍵詞:貴金屬納米顆粒;生物傳感;生物成像;藥物運(yùn)輸;腫瘤治療;生物醫(yī)學(xué)
中圖分類號(hào):TB383.1;R318.08文獻(xiàn)標(biāo)志碼:A
0引言
貴金屬納米材料是指由金(Au)、銀(Ag)、鉑(Pt)與鈀(Pb)等貴金屬制成的小尺寸納米材料.常見的形狀包括納米球、納米棒和納米星等.與其他金屬相比,貴金屬納米顆??烧{(diào)節(jié)其性質(zhì),使其具有不同的力學(xué)、電子、光學(xué)、磁性和熱力學(xué)性質(zhì).因其具有增強(qiáng)近紅外范圍的光吸收、大消光截面、增強(qiáng)光熱加熱能力、化學(xué)穩(wěn)定性和生物相容性等獨(dú)特的物理化學(xué)性質(zhì),貴金屬納米顆粒受到生物醫(yī)學(xué)領(lǐng)域的廣泛關(guān)注[1-3].
生物醫(yī)學(xué)領(lǐng)域中,目前對(duì)于生物傳感、生物成像、藥物運(yùn)輸及腫瘤治療等方面的研究逐漸增多.首先是生物傳感方面.貴金屬納米材料易于修飾,通過與抗體或半導(dǎo)體等的結(jié)合可實(shí)現(xiàn)精準(zhǔn)高效識(shí)別.借助貴金屬本身的等離激元共振可增強(qiáng)傳感器的靈敏度,因而通過貴金屬可制備高靈敏度、高穩(wěn)定性的生物傳感器.其次是生物成像方面.近些年來,生物成像在臨床醫(yī)學(xué)領(lǐng)域有廣泛的使用,以便能迅速了解組織和器官的病灶狀況從而進(jìn)行及時(shí)治療.傳統(tǒng)的有機(jī)染料作為造影劑具有光穩(wěn)性差、量子產(chǎn)率低及穩(wěn)定性不足的缺點(diǎn)[4].因此,精準(zhǔn)、穩(wěn)定且明顯的造影劑成為科研人員追逐的目標(biāo).貴金屬納米顆粒通過電子的相干振蕩引起的表面電場(chǎng)可有效地增強(qiáng)輻射特性,且其光截面和吸收面較高,使其作為造影劑在生物成像領(lǐng)域被廣泛使用.第三是藥物運(yùn)輸方面.傳統(tǒng)的藥物半衰期短且藥物進(jìn)入細(xì)胞前可能引起身體吞噬細(xì)胞的吞噬,因此治療效果不佳.除此之外,長(zhǎng)期且大量的藥物使用會(huì)導(dǎo)致身體產(chǎn)生耐藥性,從而不能有效地治療疾病.由于貴金屬納米顆粒具有易于修飾、良好的生物相容性、穩(wěn)定性和裝載性,將其作為藥物載體,通過抗體的修飾可準(zhǔn)確識(shí)別病變細(xì)胞,從而實(shí)現(xiàn)精準(zhǔn)給藥[5-7].最后是腫瘤治療方面.貴金屬納米顆粒可將藥物或?qū)?yīng)的抗體進(jìn)行裝載,通過與受體的精準(zhǔn)識(shí)別到達(dá)腫瘤.通過本身具有的化學(xué)性質(zhì)誘導(dǎo)免疫反應(yīng)進(jìn)行腫瘤治療[8-10].綜上所述,貴金屬納米顆粒憑借優(yōu)越的光學(xué)、電學(xué)、生物相容性及穩(wěn)定性等物理化學(xué)性質(zhì)在生物醫(yī)學(xué)領(lǐng)域占據(jù)重要位置[11-14].
1生物傳感
貴金屬納米材料因其獨(dú)特的化學(xué)性質(zhì)(例如光致發(fā)光及高靈敏度等)而被廣泛應(yīng)用于生物傳感方面[15-16].
Ren等[17]提出將葡萄糖氧化酶(glucose oxidase,GOx)固定在銀納米顆粒(silver nanoparticles,Ag NPs)的安培葡萄糖生物傳感器.與不含Ag NPs的傳感器進(jìn)行對(duì)比,發(fā)現(xiàn)含Ag NPs的酶電極顯著提高了響應(yīng)電流和電子轉(zhuǎn)移速率,同時(shí)也提高了生物傳感器的響應(yīng)速度,穩(wěn)態(tài)響應(yīng)時(shí)間至少提高了3倍.以此為基礎(chǔ),科研人員發(fā)現(xiàn)借助半導(dǎo)體的高電子轉(zhuǎn)移性能和低過電位,可制備高靈敏度的貴金屬納米顆粒生物傳感器.Huang等[18]提出用以二氧化鈦(TiO2)作為表面增強(qiáng)拉曼散射(surface enhanced Raman scattering,SERS)基底,與Ag NPs結(jié)合后形成的SERS生物傳感器(Ag NPs/TiO2)來檢測(cè)尿嘧啶脫氧核糖核酸(deoxyribonucleic acid,DNA)糖醛酶(uracil DNA glycosylase,UDG).借助等離子共振與電荷轉(zhuǎn)移的協(xié)同效應(yīng),提高了拉曼強(qiáng)度和靈敏度,并且檢測(cè)限較低,約為1.200×10-5 U mL-1.
鉑納米顆粒(platinum nanoparticles,Pt NPs)不僅具有良好的生物相容性和穩(wěn)定性,還可有效地降低過氧化氫氧化/還原的過電壓和快速響應(yīng)[19-21].Kang等[22]制備金-鉑納米粒子修飾的TiO2納米管電極作為葡萄糖傳感器.該傳感器在0~1.800 mM范圍內(nèi)具有較高的靈敏度,響應(yīng)時(shí)間為3 s,檢測(cè)限為0.100 mM.后來,Zhang等[23]將Pt NPs的低過電位性與石墨烯(gragphene oxide,GO)的高比表面積性相結(jié)合,形成高靈敏度的安培生物傳感器.該傳感器在0.500 μM~3.475 mM范圍內(nèi),檢測(cè)限大約為0.200 μM,比Pt NPs具有更高的靈敏度(459±3 mA M-1cm-2,n=5).Pt NPs雖可有效降低過氧化氫的過電位,但是形成的傳感器的靈敏度和穩(wěn)定性仍不夠高且檢測(cè)限仍不夠低.
金納米顆粒(gold nanoparticles,Au NPs)具有可協(xié)調(diào)的光學(xué)特性、高穩(wěn)定性和生物相容性,并且在光穩(wěn)定性方面更為優(yōu)越[24-25].Lane等[26]發(fā)現(xiàn)功能化的金納米棒附著在癌細(xì)胞上時(shí),拉曼信號(hào)得到極大增強(qiáng).另外,功能化的金納米棒因與癌細(xì)胞有很強(qiáng)的親和力,因此選擇性檢測(cè)成為了可能.以此為基礎(chǔ),Wang等[27]合成MoS2-Au免疫傳感器以檢測(cè)癌胚抗原(carcinoembryonic antigen,CEA)(見圖1(a)).該傳感器經(jīng)過二硫化鉬(MoS2)的修飾,提高了電導(dǎo)率、生物相容性和比表面積,能更有效地固定抗體,可使CEA濃度在1 pg/mL至50 ng/mL的范圍內(nèi)測(cè)定,檢測(cè)限為0.270 pg/mL(見圖1(b)).為提高傳感器的靈敏度,科研人員將抗體與貴金屬納米顆粒進(jìn)行偶聯(lián)形成傳感器.Kabiraz等[28]使用抗體標(biāo)記的Au NPs(Ab-Au NP)制備免疫傳感器.通過間接競(jìng)爭(zhēng)抑制免疫分析法可知,該傳感器具有更低的檢測(cè)限(0.050 pg/mL),比抗體低50倍.借助GO的孔狀結(jié)構(gòu)、高電導(dǎo)率和電子轉(zhuǎn)移速率,也可增強(qiáng)傳感器的性能.Wong等[29]借助協(xié)同作用,構(gòu)建對(duì)腎上腺素和尿酸的Au NPs/GO傳感器.通過差分脈沖伏安法分析,傳感器對(duì)腎上腺素和尿酸的檢測(cè)限分別為1.000×10-7 mol/L和5.000×10-8 mol/L.后來,科研人員發(fā)現(xiàn),共價(jià)有機(jī)框架(covalent organic framework,COFs)穩(wěn)定性和永久孔隙度高且低密度好,通過Au NPs和COFs結(jié)合使其具有更大比表面積,從而提供更多識(shí)別位點(diǎn).檢測(cè)限可達(dá)到0.270 pg/mL,[27]樣品回收率可達(dá)87.000%~101.700%[30].
2生物成像
貴金屬中,電子在導(dǎo)帶內(nèi)的相干集體振蕩引起了較大的表面電場(chǎng),極大增強(qiáng)了輻射特性.因此,納米顆粒的光散射截面和吸收截面比其他有機(jī)染料更強(qiáng),這使得貴金屬納米顆粒成為性能優(yōu)良的生物成像劑[31-32].
Au NPs具有穩(wěn)定性強(qiáng)等優(yōu)良的化學(xué)性質(zhì),且在輻射光譜的近紅外(near-infrared,NIR)區(qū)域活躍,可減少天然組織中固有的發(fā)色團(tuán)的光滅絕[33-34].Wang等[31]合成平均直徑為135 nm的Au NPs作為造影劑,對(duì)其成像進(jìn)行了深入研究.經(jīng)過循環(huán)動(dòng)力學(xué)的分析,在3次注射后,納米殼的光聲學(xué)對(duì)比度提高了63%,提高了皮質(zhì)血容量測(cè)量的敏感度,后來應(yīng)用金納米籠作為成像劑,與空白進(jìn)行對(duì)比,注射2 h后的增強(qiáng)效果峰值為81%.Harmsen等[35]用表面增強(qiáng)共振拉曼散射Au NPs精確地顯示了腫瘤邊緣、腫瘤侵襲和多灶局部腫瘤擴(kuò)散.在近乎臨床成像條件(激光功率為10~100 mW和實(shí)時(shí)成像)下,采用拉曼成像準(zhǔn)確對(duì)原發(fā)性腫瘤的癌前病變進(jìn)行標(biāo)記.通過觀察到的胰腺上皮內(nèi)瘤變前體,可知有發(fā)生癌變的可能,從而達(dá)到提前檢測(cè)的效果.
Pt NPs具有較小的尺寸和較低的細(xì)胞毒性,與Au NPs相比,可在470 nm處發(fā)出更亮的熒光[36-37].除此之外,Pt NPs可通過π-π和封閉殼的親金屬之間的相互作用,從而降低環(huán)境變化的干擾.Tanaka等[38]利用簡(jiǎn)單的化學(xué)法和高效液相色譜法(high performance liquid chromatography,HPLC)純化制得Pt NPs作為造影劑,通過結(jié)合蛋白將抗體與Pt團(tuán)簇組合進(jìn)行細(xì)胞成像,如圖2(a)所示.經(jīng)過48 h后,細(xì)胞活性仍超過85%,如圖2(b)所示,這表明該造影劑具有較低的毒性.為獲得更高的發(fā)射量子產(chǎn)率和更長(zhǎng)激發(fā)態(tài)壽命,Septiadi等[39]制備了高量子產(chǎn)率和低激發(fā)態(tài)的自組裝Pt(II)系統(tǒng),其激發(fā)態(tài)低至543 nm.通過對(duì)金屬配合物進(jìn)行標(biāo)記,證明通過細(xì)胞對(duì)其的吸收進(jìn)行定位,從而實(shí)現(xiàn)細(xì)胞成像.
NIR納米材料在活性組織中具有較高的透明度和較低的自熒光度,在生物成像方面具有較大的優(yōu)勢(shì).但是,NIR納米材料具有高毒性.Ag NPs憑借著自身低毒性和高光學(xué)活性脫穎而出[33].除此之外,Ag NPs的光學(xué)截面也相較其他金屬而言更高,從而具有更好的散射性能.Wang等[40]通過簡(jiǎn)單的水相法制備了硫化銀納米團(tuán)簇(silver sulfide nanoclusters,Ag2S NCs).合成的Ag2S NCs可在624~724 nm范圍內(nèi)進(jìn)行調(diào)制發(fā)光.通過其在NIR區(qū)域連續(xù)24 h發(fā)射679 nm的光,能夠觀察到細(xì)胞的明亮視野(見圖3(a)),且在經(jīng)過48 h后,細(xì)胞活性仍在80%以上(見圖3(b)).由于Ag NPs在小尺寸下具有一定的毒性,對(duì)細(xì)胞有損傷,因此Manivannan等[41]通過將SiO2包裹在Ag NPs表面達(dá)到降低毒性的目的.對(duì)其毒性進(jìn)行檢測(cè)發(fā)現(xiàn),即使在黑暗的環(huán)境下,90%細(xì)胞仍然存活,且在NIR光照射下,可以觀察到明亮的圖像.
3藥物運(yùn)輸
傳統(tǒng)進(jìn)行腫瘤治療的藥物可隨腫瘤組織擴(kuò)散到健康組織,從而分散到全身各處.但是,藥物的半衰期較短,到達(dá)病灶的藥量較少,將造成大量的浪費(fèi)和低治療效果,并且長(zhǎng)期大量用藥可能會(huì)導(dǎo)致身體產(chǎn)生耐藥性,從而治療效果不明顯[42-43].為解決上述問題,科研人員將貴金屬納米顆粒作為藥物載體進(jìn)行藥物傳輸.
Au NPs由于其具有易制備、生物惰性及可控制藥物釋放等優(yōu)勢(shì),被廣泛應(yīng)用于藥物載體.金屬納米顆粒為靶向藥物傳遞和增加藥物通透性提供了可能性.Dykman等[44]通過將肽和Au NPs組合,獲得用于藥物傳遞的載體.通過該載體控制免疫反應(yīng),比如小鼠的巨噬細(xì)胞能識(shí)別耦聯(lián)物而不能識(shí)別單獨(dú)的金屬納米顆粒或肽,因此在耦聯(lián)物存在的情況下巨噬細(xì)胞不會(huì)增殖且藥物可安全通過免疫屏障到達(dá)病灶.除此之外,為了提高靶向效果,將Au NPs與RGD肽進(jìn)行組合.對(duì)實(shí)驗(yàn)進(jìn)行分析可知,基于RGD功能化Au NPs的小干擾RNA(small interfering RNA,siRNA)傳遞系統(tǒng)可以成功抑制腫瘤細(xì)胞增殖,減小腫瘤大小.除了對(duì)腫瘤藥物進(jìn)行輸送外,在疫苗佐劑方面也具有巨大潛力.Xu等[45]制備了表面工程金納米棒(gold nanorods,Au NRs)作為疫苗佐劑,用于艾滋病病毒治療.與體內(nèi)裸艾滋病病毒-1包膜糖蛋白抗體(HIV-1 Env)相比,Au NRs可以通過激活抗原達(dá)到較強(qiáng)的免疫應(yīng)答及T細(xì)胞增殖的效果.為制備具有更強(qiáng)的載藥能力和穩(wěn)定性的高效載體,Wang等[46]建立了基于硫醇功能化的兩親性二嵌段共聚物穩(wěn)定的Au NPs的給藥體系.根據(jù)紫外分析得知,與其他小分子修飾的Au NRs相比,構(gòu)建的復(fù)合材料在14 d內(nèi)具有良好的穩(wěn)定性,并且載藥能力更強(qiáng).每個(gè)Au NPs可裝載460個(gè)藥物分子.
Ag NPs因具有低毒性和可調(diào)控的光學(xué)能力,且在藥物運(yùn)輸方面具有裝載和釋放效率高且穩(wěn)定性高、生物相容性好等重要作用[47]而受到關(guān)注.Wang等[48]通過一步合成法使用葉酸包被Ag NPs和阿霉素(doxorubicin,DOX),用于藥物DOX的輸送.利用Ag NPs的增強(qiáng)拉曼散射和葉酸與癌細(xì)胞表面受體的結(jié)合對(duì)癌細(xì)胞進(jìn)行定位,從而實(shí)現(xiàn)SERS成像.通過對(duì)DOX檢測(cè)發(fā)現(xiàn),4 h后DOX釋放到細(xì)胞質(zhì).值得注意的是,該載體雖比單獨(dú)DOX毒性小,但與其他組合形式相比仍具有較高的毒性.Ravindra等[49]通過將Ag NPs和姜黃素嵌入到水凝膠中,用于姜黃素的輸送.通過對(duì)照實(shí)驗(yàn)發(fā)現(xiàn),含有Ag NPs的藥物加載率(79.2%)最高.與普通聚水凝膠相比,姜黃素負(fù)載Ag NPs或銀離子復(fù)合水凝膠的釋放效率更高且釋放較為緩慢,這為長(zhǎng)期有效治療傷口提供了可能.
4腫瘤治療
貴金屬納米顆粒不僅可以作為生物傳感器、生物成像的造影劑與藥物運(yùn)輸?shù)妮d體,其本身與藥物的結(jié)合也可以作為癌癥治療的藥物.貴金屬納米材料的低毒性和高細(xì)胞活性是臨床腫瘤治療的優(yōu)勢(shì)條件,為腫瘤治療提供了新的方向.
Au NPs由于其表面等離子共振增強(qiáng)的光散射和吸收,在癌癥診斷和治療方面具有巨大潛力.Jain等[50]首先提出借助Au NPs吸收的光轉(zhuǎn)化的局部熱和靶向標(biāo)記癌細(xì)胞實(shí)現(xiàn)特異性的癌癥治療.在光能量為19 W/cm2和25 W/cm2 的照射下,Au NPs作為光熱劑可對(duì)口腔鱗狀癌細(xì)胞進(jìn)行細(xì)胞消融.4 min后,癌細(xì)胞遭受光熱損傷至半,而未被Au NPs標(biāo)記的細(xì)胞無任何損傷[50].以此實(shí)驗(yàn)為基礎(chǔ),科研人員對(duì)Au NPs進(jìn)行了深入研究.Yang等[51]在2018年提出對(duì)DOX結(jié)合的多孔Pt NPs包裹Au NPs的納米顆粒(Au@Pt NPs)在化學(xué)—光熱共療法中抑制腫瘤生長(zhǎng)作用進(jìn)行研究.通過對(duì)腫瘤的細(xì)胞存活率進(jìn)行檢測(cè)發(fā)現(xiàn),光照后癌細(xì)胞急劇下降,腫瘤的體積明顯收縮.為解決仿生納米酶在缺氧腫瘤中未得到更優(yōu)的活性,Yang等[52]在2020年提出一種棒狀仿生雜交無機(jī)納米酶(MnO2-Au).合成的納米酶即使在高濃度下對(duì)細(xì)胞的毒性也非常小,細(xì)胞活性在95%以上,如圖4(a)所示.Au NPs可以穩(wěn)定且有效地催化葡萄糖在惡劣的腫瘤微環(huán)境下氧化,從而使腫瘤細(xì)胞對(duì)熱消融敏感,實(shí)現(xiàn)光熱治療,如圖4(b)所示.通過此過程,可有效解決缺氧問題,從而提高物理療法(physical therapy,PT)的療效.
Ag NPs作為貴金屬納米顆粒具有多功能性,可使藥物與親和配體在同一載體上,用于靶向和可追蹤的藥物傳遞,解決耐藥性和深入腫瘤治療的難題[53-54].Chen等[55]為解決癌癥異質(zhì)性和適應(yīng)性耐藥性帶來的困難,將活性腫瘤靶向三肽與Ag NPs結(jié)合,用于DOX的釋放以消除腫瘤細(xì)胞.通過對(duì)小鼠成活情況進(jìn)行監(jiān)測(cè),得知該方式對(duì)腫瘤有明顯的抑制效果,其抑制率約為70%,小鼠的成活率在70%以上,并且腫瘤周圍和腫瘤中心均表現(xiàn)出大面積凋亡和壞死.Shi等[56]借助GO與Ag NPs的協(xié)同作用成功提高載藥能力和靶向治療能力.合成的納米顆粒(GO@Ag)載藥能力達(dá)到82%,且具有良好的穩(wěn)定性.在腫瘤的靶向治療中,除藥物體系(Ag2S-DOX-cRGD)本身可釋放DOX外,NIR照射也可刺激DOX的釋放.當(dāng)Ag2S-DOX-cRGD濃度達(dá)到4 μg/mL時(shí),腫瘤細(xì)胞的活性不到10%(如圖5(a)所示),且通過對(duì)體內(nèi)X射線成像可明顯地觀察到腫瘤細(xì)胞的減?。ㄈ鐖D5(b)所示).建立的腫瘤治療系統(tǒng)雖具有較優(yōu)的治療效果,但對(duì)腫瘤深度穿透能力仍有限.為解決此問題,Xu等[57]提出了一種高效的金銀納米復(fù)合材料(Au-Ag-BTSHNTs).該復(fù)合材料不僅可促進(jìn)線粒體凋亡因子的表達(dá),還可以利用被酸性腫瘤微環(huán)境觸發(fā)生成的二氧化硫(SO2)進(jìn)行深度腫瘤的治療.在光熱治療時(shí),該復(fù)合材料誘導(dǎo)釋放的SO2氣體可深入腫瘤細(xì)胞誘導(dǎo)產(chǎn)生活性氧和熱療,從而引起凋亡因子的表達(dá),最終導(dǎo)致細(xì)胞凋亡.
在光動(dòng)力治療(photodynamic therapy,PDT)和電動(dòng)力治療(electrodynamic therapy,EDT)中,Pt NPs因具有良好的生物相容性、NIR吸收特性和較高的腫瘤富集效果而占據(jù)重要的位置[58-59].眾所周知,大多數(shù)腫瘤中的缺氧性質(zhì)會(huì)降低PDT的治療效果.為解決此問題,Wei等[60]建立了Pt NPs包裹鈀納米顆粒與光敏劑相結(jié)合的納米系統(tǒng)(Pd@Pt-PEG-Ce6),如圖6(a)所示.Pd@Pt具有高過氧化氫酶活性,可解決缺氧的限制.進(jìn)行體內(nèi)腫瘤治療時(shí),若沒有激光或只有激光存在,則不能觀察到對(duì)癌細(xì)胞的抑制.在808 nm和660 nm激光照射下,可觀察到腫瘤在第6 d完全消除,如圖6(b)所示.除此之外,利用Pt與碳的結(jié)合(Pt/C),也可實(shí)現(xiàn)PDT治療.Pt/C借助本身的過氧化氫酶性質(zhì),分解過氧化氫以提供氧,通過光敏劑上的光將氧轉(zhuǎn)化為活性氧,從而殺死癌細(xì)胞[61].對(duì)于Pt在EDT中的性能,Lu等[62]進(jìn)行了詳細(xì)研究.通過GOx消耗癌細(xì)胞內(nèi)的葡萄糖可造成癌細(xì)胞的“饑餓”,從而對(duì)癌細(xì)胞進(jìn)行傷害.而分解葡萄糖產(chǎn)生的過氧化氫可通過Pt進(jìn)行分解產(chǎn)生氧氣,從而促進(jìn)葡萄糖的分解形成循環(huán).通過對(duì)體內(nèi)抗腫瘤實(shí)驗(yàn)的分析,在5 mA方波電刺激下,經(jīng)過14 d EDT治療后發(fā)現(xiàn)腫瘤的重量至少降低70%(約為0.2 g).因此,該復(fù)合材料可使EDT治療發(fā)揮良好的效果.
5結(jié)論與展望
貴金屬納米顆粒具有優(yōu)良的物理化學(xué)性質(zhì),在生物傳感、生物成像、藥物運(yùn)輸及腫瘤治療方面發(fā)揮了重要作用,其易于修飾且通過與半導(dǎo)體結(jié)合的協(xié)同作用成功提高了傳感器的靈敏度.除此之外,借助貴金屬納米顆粒高光散截面和吸收截面,實(shí)現(xiàn)了對(duì)腫瘤和癌細(xì)胞的精準(zhǔn)標(biāo)記和明顯成像.在生物成像觀察到病灶的組織情況后,科研人員把貴金屬納米顆粒用于腫瘤治療,其高載藥率和釋放率可有效避免半衰期短和耐藥性差的缺陷,并且可引發(fā)其他反應(yīng)(例如誘導(dǎo)癌細(xì)胞產(chǎn)生裂解酶等)進(jìn)行腫瘤治療.
貴金屬納米顆粒對(duì)生物醫(yī)學(xué)領(lǐng)域的發(fā)展具有一定的助力,但仍存在一些問題.在生物傳感方面,納米顆粒進(jìn)行傳感時(shí)靈敏度和檢測(cè)限仍不夠好.在生物成像方面,納米顆粒毒性仍不能被忽略或消除,且納米顆粒不能全部與被成像細(xì)胞結(jié)合,仍有損失.在藥物運(yùn)輸方面,雖裝載量較高,但是不能實(shí)現(xiàn)與藥物的完全結(jié)合,并且藥物的釋放率不能達(dá)到100%,因此對(duì)癌癥治療效果仍有影響.在腫瘤治療方面,雖然可以明顯地看出腫瘤治療的效果,但治療的成功率仍需提高.貴金屬納米顆粒具有如此多的缺點(diǎn),但其獨(dú)特且優(yōu)異的化學(xué)性質(zhì)若在未來與其他物質(zhì)的性能相結(jié)合,必將對(duì)現(xiàn)存問題的解決及生物醫(yī)學(xué)的發(fā)展有極大的推動(dòng).
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(實(shí)習(xí)編輯:黃愛明)
Application Progress of Noble Metal Nanomaterials
in Biomedical Field
LIU Xiaoyang,CHEN Jiaqi,F(xiàn)ENG Wei(School of Mechanical Engineering,Chengdu University,Chengdu 610106,China)Abstract:Compared with traditional medical methods,noble metal nanoparticles have good biocompatibility,stability,strong light absorption and other properties,and can perform plasma absorption in the visible and near-infrared regions.Therefore,it quickly occupies a place in the biomedical field.On this basis,the performances of noble metal nanoparticles (Ag NPs,Au NPs,Pt NPs) and their combinations with other substances (TiO2,glucose oxidase,antibodies,vaccines,etc.) in biosensor,bioimaging,drug transport and tumor treatment are discussed in this paper.Finally,the application advantages of noble metal nanoparticles in the field of nanomedicine are summarized and the existing problems and expectations for the future are pointed out.
Key words:noble metal nanoparticles;biosensing;bioimaging;drug delivery;cancer therapy;biomedicine