CN110585447B - 一种可用作声敏剂的聚集发光纳米颗粒材料的制备方法及用途 - Google Patents
一种可用作声敏剂的聚集发光纳米颗粒材料的制备方法及用途 Download PDFInfo
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Abstract
本发明公开一种可用作声敏剂的聚集发光纳米颗粒材料的制备方法及用途,包括如下步骤:(1)称取四[四‑(4‑氨苯基)]苯基乙烯(TAPE)溶于氯仿中,得到溶液A;称取脂质体溶于氯仿中,得到溶液B;将溶液A加入到溶液B中;(2)常温下,采用旋转蒸发除去氯仿,得到TAPE‑lipid纳米颗粒脂质膜C;(3)在圆底烧瓶中加入超纯水使TAPE‑lipid纳米颗粒脂质膜C溶解;(4)置于超声细胞破碎仪进行超声处理后。本申请所制备的纳米颗粒解决了水溶性的AIE材料在生物体内的应用,同时开发了新型功能,结合成像功能和超声激活功能,可实现肿瘤的诊断‑治疗一体化功能,在纳米医药、疾病诊断和克服肿瘤缺氧限制的治疗等领域具有重要的应用前景。
Description
技术领域
本发明涉及纳米医学技术领域。具体地说是一种可用作声敏剂的聚集发光纳米颗粒材料的制备方法。
背景技术
声动力疗法(SDT)通过超声激发声敏剂,在声致发光引起的声裂解过程中,通过将能量传递给氧气分子或者水分子产生高活性的单线态氧和自由基等活性氧簇(ROS)来杀伤肿瘤细胞,而达到***目的。声动力疗法具有穿透深,非侵入和时空可控等优势而成为近年来肿瘤治疗领域的研究热点,而声敏剂的研发是生动力疗法发展的关键。
四[四-(4-氨苯基)]苯基乙烯(TAPE),如下式所示:
作为四苯基乙烯衍生物,由于具有能自由旋转的***苯环的螺旋桨形结构,是一种典型的AIE荧光发光团,被广泛应用于电导研究、功能材料、传感、成像等多个重要领域,然而,在疾病治疗领域的应用还非常空缺。此外,水溶性差是其在生物研究和疾病治疗领域广泛研究的主要屏障。因此,设计生物相容的纳米颗粒、开发其在治疗领域的新功能,为AIE材料的研究和应用领域提供思路。
发明内容
为此,本发明所要解决的技术问题在于提供一种水溶性良好的具有聚集发光功能的可用作声敏剂的聚集发光纳米颗粒材料的制备方法。
为解决上述技术问题,本发明提供如下技术方案:
一种可用作声敏剂的聚集发光纳米颗粒材料的制备方法,采用薄膜法制备纳米颗粒,包括如下步骤:
(1)称取四[四-(4-氨苯基)]苯基乙烯溶于氯仿中,得到溶液A;称取脂质体溶于氯仿中,得到溶液B;将溶液A加入到溶液B中,常温搅拌至溶;
(2)常温下,采用旋转蒸发仪在真空条件下旋转蒸发除去氯仿,观察圆底烧瓶内无溶剂时,将循环水式多用真空泵调至最大真空度再旋蒸一定时间,至全干,得到TAPE-lipid纳米颗粒脂质膜C;
(3)在圆底烧瓶中加入超纯水使TAPE-lipid纳米颗粒脂质膜C溶解后,转移到离心管中;
(4)将离心管置于超声细胞破碎仪进行超声处理后,得到TAPE-lipid悬液D,超滤膜过滤后得到TAPE-lipid纳米颗粒溶液,放入4℃冰箱中保存备用。
上述可用作声敏剂的聚集发光纳米颗粒材料的制备方法,在步骤(1)中,所述四[四-(4-氨苯基)]苯基乙烯和所述脂质体的质量比为1:5-20。
上述可用作声敏剂的聚集发光纳米颗粒材料的制备方法,在步骤(2)中,观察圆底烧瓶内无溶剂时,将循环水式多用真空泵调至最大真空度再旋蒸2-10min,后在45℃条件下旋蒸至全干。
上述可用作声敏剂的聚集发光纳米颗粒材料的制备方法,在步骤(3)中,在瓶中加入1-10mL超纯水使其溶解后转移到10-50mL离心管中。
上述可用作声敏剂的聚集发光纳米颗粒材料的制备方法,在步骤(4)中,超声细胞破碎仪的额定功率为150W、频率为20kHz,超声功率为额定功率的20%-90%,超声时间为3-10min。
上述可用作声敏剂的聚集发光纳米颗粒材料的制备方法,所述脂质体为大豆卵磷脂和胆固醇的混合物;大豆卵磷脂和胆固醇的质量比为:大豆卵磷脂:胆固醇=(5~3):1。
上述可用作声敏剂的聚集发光纳米颗粒材料的制备方法,称取3.6mg的TAPE溶解于1mL氯仿中,得到溶液A;54mg大豆卵磷脂和18mg胆固醇溶于20mL氯仿中,得到混合溶液B;将溶液A加入混合溶液B中;常温搅拌至溶后,置于旋转蒸发仪中,常温下旋转蒸发去除有机溶剂,观察瓶内无溶剂时,用最大真空度再旋5min,后在45℃下旋至全干,即得TAPE-lipid纳米颗粒脂质膜C;在瓶中加入4mL超纯水使其溶解后转移到10mL离心管中,于超声清洗波中超声水化15min,得到TAPE脂质体悬液D;超声细胞破碎仪的额定功率为150W、频率为20kHz,超声功率为额定功率的30%,时间为5min,超声处理后,再经孔径为0.22μm超滤膜过滤后,得到TAPE-lipid纳米颗粒溶液。
上述可用作声敏剂的聚集发光纳米颗粒材料的制备方法,称取3.6mg的TAPE溶解于1mL氯仿中,得到溶液A;54mg大豆卵磷脂和18mg胆固醇溶于10mL氯仿中,得到混合溶液B;将溶液A加入混合溶液B中;常温搅拌至溶后,置于旋转蒸发仪中,常温下旋转蒸发去除有机溶剂,观察瓶内无溶剂时,用最大真空度再旋5min,后在45℃下旋至全干,即得TAPE-lipid纳米颗粒脂质膜C;在瓶中加入3mL超纯水使其溶解后转移到10mL离心管中,于超声清洗波中超声水化15min,得到TAPE脂质体悬液D;超声细胞破碎仪的额定功率为150W、频率为20kHz,超声功率为额定功率的30%,时间为5min,超声处理后,再经孔径为0.22μm超滤膜过滤后,得到TAPE-lipid纳米颗粒溶液。
上述可用作声敏剂的聚集发光纳米颗粒材料的制备方法,称取3.6mg的TAPE溶解于1mL氯仿中,得到溶液A;54mg大豆卵磷脂和18mg胆固醇溶于20mL氯仿中,得到混合溶液B;将溶液A加入混合溶液B中;常温搅拌至溶后,置于旋转蒸发仪中,常温下旋转蒸发去除有机溶剂,观察瓶内无溶剂时,用最大真空度再旋5min,后在45℃下旋至全干,即得TAPE-lipid纳米颗粒脂质膜C;在瓶中加入4mL超纯水使其溶解后转移到10mL离心管中,于超声清洗波中超声水化15min,得到TAPE脂质体悬液D;超声细胞破碎仪的额定功率为150W、频率为20kHz,超声功率为额定功率的30%,时间为5min,超声处理后,再经孔径为0.22μm超滤膜过滤后,得到TAPE-lipid纳米颗粒溶液。
聚集发光纳米颗粒材料的用途,上述聚集发光纳米颗粒材料在声动力***过程中作为声敏剂使用。
本发明的技术方案取得了如下有益的技术效果:
1、四[四-(4-氨苯基)]苯基乙烯作为典型的AIE材料,其水溶性差严重限制了其在生物体内的应用,通过与两亲性载体制成纳米颗粒,增加了其在水中的溶解性,提高了在生物体内的应用价值;本发明的关键点在制备的纳米脂质体颗粒,克服了聚集发光材料的水溶性差的问题,更有利于应用到生物体内的成像探针。
2、荧光成像显示,该纳米颗粒的水溶液在800nm附近具有明显的荧光信号,可作为荧光探针应用于生物体内的荧光成像;此外,该纳米颗粒的荧光强度随着浓度的增加呈现增强的趋势,这一聚集发光的功能有利于生物体内的药物检测及点亮生物体病灶组织的功能,为实时监控药物富集和治疗提供依据。
3、进一步的超声激发显示,该纳米颗粒还可以在超声激发下产生单线态氧,单线态氧具有杀伤肿瘤细胞的功能,因此,该纳米颗粒可用做声敏剂,用于生动力***的功能,这一性质为其作为诊断-治疗一体化生物材料提供了依据。
该纳米颗粒解决了水溶性的AIE材料在生物体内的应用,同时开发了新型功能,结合成像功能和超声激活功能,可实现肿瘤的诊断-治疗一体化功能,在纳米医药、疾病诊断和克服肿瘤缺氧限制的治疗等领域具有重要的应用前景。
附图说明
图1本发明可用作声敏剂的聚集发光纳米颗粒材料的制备方法的合成路线图;
图2本发明可用作声敏剂的聚集发光纳米颗粒材料的制备方法得到的TAPE-Lipid纳米颗粒(四[四-(4-氨苯基)]苯基乙烯-脂质体纳米颗粒)的电镜图;
图3四[四-(4-氨苯基)]苯基乙烯TAPE-脂质体纳米颗粒的荧光强度随浓度的增加而增强图;
图4纳米颗粒在超声激发后产生的单线态氧使DPBF的吸收值发生猝灭图。
具体实施方式
第一部分、可用作声敏剂的聚集发光纳米颗粒材料的制备(四[四-(4-氨苯基)]苯
基乙烯TAPE-脂质体纳米颗粒)
实施例1:
TAPE-脂质体纳米颗粒的制备:取3.6mg的TAPE溶解于1mL氯仿中,得到溶液A;36mg大豆卵磷脂和12mg胆固醇溶于10mL氯仿中,得到混合溶液B;将溶液A加入混合溶液B中。常温搅拌至溶后,置于旋转蒸发仪中,常温下采用旋转蒸发仪在真空条件下旋转蒸发去除氯仿,观察瓶内无溶剂时,将循环水式多用真空泵调至最大真空度(负0.098Mpa)再旋5min,后在45℃下旋至全干,即得TAPE-lipid纳米颗粒脂质膜C。在瓶中加入2mL超纯水使其溶解后转移到10mL离心管中,于超声清洗波中超声水化15min,得到TAPE脂质体悬液D。超声细胞破碎仪(sonics&meterials inc,USA)的额定功率为150W、频率为20kHz,超声功率为额定功率的30%,时间为5min,超声处理后,再经孔径为0.22μm超滤膜过滤后,得到TAPE-lipid纳米颗粒溶液。
实施例2:
TAPE-脂质体纳米颗粒的制备:称取3.6mg的TAPE溶解于1mL氯仿中,得到溶液A;54mg大豆卵磷脂和18mg胆固醇溶于10mL氯仿中,得到混合溶液B;将溶液A加入混合溶液B中。常温搅拌至溶后,置于旋转蒸发仪中,常温下旋转蒸发仪在真空条件下旋转蒸发去除氯仿,观察瓶内无溶剂时,将循环水式多用真空泵调至最大真空度(负0.098Mpa)再旋5min,后在45℃下旋至全干,即得TAPE-lipid纳米颗粒脂质膜C。在瓶中加入3mL超纯水使其溶解后转移到10mL离心管中,于超声清洗波中超声水化15min,得到TAPE脂质体悬液D。超声细胞破碎仪(sonics&meterials inc,USA)的额定功率为150W、频率为20kHz,超声功率为额定功率的30%,时间为5min,超声处理后,再经孔径为0.22μm超滤膜过滤后,得到TAPE-lipid纳米颗粒溶液。
实施例3:
TAPE-脂质体纳米颗粒的制备:称取3.6mg的TAPE溶解于1mL氯仿中,得到溶液A;54mg大豆卵磷脂和18mg胆固醇溶于20mL氯仿中,得到混合溶液B;将溶液A加入混合溶液B中。常温搅拌至溶后,置于旋转蒸发仪中,常温下旋转蒸发仪在真空条件下旋转蒸发去除有机溶剂,观察瓶内无溶剂时,将循环水式多用真空泵调至最大真空度(负0.098Mpa)再旋5min,后在45℃下旋至全干,即得TAPE-lipid纳米颗粒脂质膜C。在瓶中加入4mL超纯水使其溶解后转移到10mL离心管中,于超声清洗波中超声水化15min,得到TAPE脂质体悬液D。超声细胞破碎仪(sonics&meterials inc,USA)的额定功率为150W、频率为20kHz,超声功率为额定功率的30%,时间为5min,超声处理后,再经孔径为0.22μm超滤膜过滤后,得到TAPE-lipid纳米颗粒溶液。
图1为实施例1至实施例3中TAPE-lipid纳米颗粒的合成示意图,实施例1至实施例3均能得到大小均匀的纳米颗粒(如图2所示),粒径约为60nm的均匀的球状纳米颗粒。
第二部分、四[四-(4-氨苯基)]苯基乙烯-脂质体纳米颗粒的荧光特性及应用
将实施例3制得的TAPE-Lipid纳米颗粒溶液利用逐级稀释法将溶液稀释成浓度分别为2μg/mL,4μg/mL、8μg/mL、16μg/mL、32μg/mL、64μg/mL(TAPE的浓度),按照浓度由低到高的顺序,检测各个浓度溶液的荧光光谱,确定荧光强度对浓度的变化曲线。如图3所示,纳米颗粒的最大发射光谱在800nm附近,同时,随着浓度的增加,荧光强度逐渐增加,具有明显的聚集增强的特征,这一性质可用于对体内病灶组织的成像,且随着纳米颗粒在病灶组织的聚集,病灶点会越来越清晰明显,从而具有良好的成像诊断功能。
纳米颗粒溶液在超声激发下产生单线态氧的检测:将实施例3制得的TAPE-Lipid纳米颗粒溶液稀释到50ug/mL;取3mL稀释后的溶液于直径为2.5cm的培养皿中,记为溶液E;将1,3-二苯基异苯并呋喃乙醇溶液(DPBF,一种单线态氧猝灭剂)用乙醇溶解成0.5mM的溶液,取10uLDPBF溶液于E溶液中,混合均匀后,用超声治疗仪连续超声激发10~80秒,每10秒中取50微升,稀释到1mL,用紫外分光光度计检测溶液在420nm处的吸收值变化情况。由图4可知,随着超声激发时间的不断增长,420nm附近的吸收值不断下降,说明在超声激发中产生了单线态氧;单线态氧结合了DPBF,导致了吸光值降低,且随着时间的增长,单线态氧的产量不断增加,可用作声敏剂用于声动力治疗。
由此可见,本发明制备的TAPE-Lipid纳米颗粒具有对肿瘤等病灶组织的诊断-治疗一体化能力。
显然,上述实施例仅仅是为清楚地说明所作的举例,而并非对实施方式的限定。对于所属领域的普通技术人员来说,在上述说明的基础上还可以做出其它不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。而由此所引伸出的显而易见的变化或变动仍处于本专利申请权利要求的保护范围之中。
Claims (9)
1.一种可用作声敏剂的聚集发光纳米颗粒材料的制备方法,其特征在于,采用薄膜法制备纳米颗粒,包括如下步骤:
(1)称取四[四-(4-氨苯基)]苯基乙烯溶于氯仿中,得到溶液A;称取脂质体溶于氯仿中,得到溶液B;将溶液A加入到溶液B中,常温搅拌至溶;
(2)常温下,采用旋转蒸发仪在真空条件下旋转蒸发除去氯仿,观察圆底烧瓶内无溶剂时,将循环水式多用真空泵调至最大真空度再旋蒸一定时间,至全干,得到TAPE-lipid纳米颗粒脂质膜C;
(3)在圆底烧瓶中加入超纯水使TAPE-lipid纳米颗粒脂质膜C溶解后,转移到离心管中;
(4)将离心管置于超声细胞破碎仪进行超声处理后,得到TAPE-lipid悬液D,超滤膜过滤后得到TAPE-lipid纳米颗粒溶液,放入4℃冰箱中保存备用。
2.根据权利要求1所述的可用作声敏剂的聚集发光纳米颗粒材料的制备方法,其特征在于,在步骤(1)中,所述四[四-(4-氨苯基)]苯基乙烯和所述脂质体的质量比为1:5-20。
3.根据权利要求1所述的可用作声敏剂的聚集发光纳米颗粒材料的制备方法,其特征在于,在步骤(2)中,观察圆底烧瓶内无溶剂时,将循环水式多用真空泵调至最大真空度再旋蒸2-10min,后在45℃条件下旋蒸至全干。
4.根据权利要求1所述的可用作声敏剂的聚集发光纳米颗粒材料的制备方法,其特征在于,在步骤(3)中,在瓶中加入1-10mL超纯水使其溶解后转移到10-50mL离心管中。
5.根据权利要求1所述的可用作声敏剂的聚集发光纳米颗粒材料的制备方法,其特征在于,在步骤(4)中,超声细胞破碎仪的额定功率为150W、频率为20kHz,超声功率为额定功率的20%-90%,超声时间为3-10min。
6.根据权利要求1-5任一所述的可用作声敏剂的聚集发光纳米颗粒材料的制备方法,其特征在于,所述脂质体为大豆卵磷脂和胆固醇的混合物;大豆卵磷脂和胆固醇的质量比为:大豆卵磷脂:胆固醇=(5~3):1。
7.根据权利要求6所述的可用作声敏剂的聚集发光纳米颗粒材料的制备方法,其特征在于,称取3.6mg的TAPE溶解于1mL氯仿中,得到溶液A;54 mg 大豆卵磷脂和18 mg 胆固醇溶于20 mL氯仿中,得到混合溶液B;将溶液A加入混合溶液B中;常温搅拌至溶后,置于旋转蒸发仪中,常温下旋转蒸发去除有机溶剂,观察瓶内无溶剂时,用最大真空度再旋5min,后在45℃下旋至全干,即得TAPE-lipid纳米颗粒脂质膜C;在瓶中加入4mL超纯水使其溶解后转移到10mL离心管中,于超声清洗波中超声水化15min,得到TAPE脂质体悬液D;超声细胞破碎仪的额定功率为150W、频率为20kHz,超声功率为额定功率的30%,时间为5min,超声处理后,再经孔径为0.22μm超滤膜过滤后,得到TAPE-lipid纳米颗粒溶液。
8.根据权利要求6所述的可用作声敏剂的聚集发光纳米颗粒材料的制备方法,其特征在于,称取3.6mg的TAPE溶解于1mL氯仿中,得到溶液A;54 mg 大豆卵磷脂和18 mg 胆固醇溶于10 mL氯仿中,得到混合溶液B;将溶液A加入混合溶液B中;常温搅拌至溶后,置于旋转蒸发仪中,常温下旋转蒸发去除有机溶剂,观察瓶内无溶剂时,用最大真空度再旋5min,后在45℃下旋至全干,即得TAPE-lipid纳米颗粒脂质膜C;在瓶中加入3mL超纯水使其溶解后转移到10mL离心管中,于超声清洗波中超声水化15min,得到TAPE脂质体悬液D;超声细胞破碎仪的额定功率为150W、频率为20kHz,超声功率为额定功率的30%,时间为5min,超声处理后,再经孔径为0.22μm超滤膜过滤后,得到TAPE-lipid纳米颗粒溶液。
9.聚集发光纳米颗粒材料的用途,其特征在于,权利要求1-8任一所制备的聚集发光纳米颗粒材料在制备声敏剂中的应用。
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