摘要
目的:制备出基于黑磷纳米片(black phosphorus nanosheets,BPNSs)的智能近红外光(near-infrared light,NIR)响应复合水凝胶,用于骨肉瘤的光热-化疗协同治疗.方法:采用液相剥离的方式制备BPNSs,并利用静电作用原理,以聚乙二醇二胺[PEG-(NH2)2]为修饰剂对其进行改性.改性后的BPNSs再次通过静电作用高效地装载药物阿霉素(adriamycin,DOX).将经过PEG改性并负载DOX的BPNSs共混于海藻酸钠/泊洛沙姆复合水凝胶基质中,通过冷法制备基于BPNSs的智能近红外光响应复合水凝胶.以小鼠骨肉瘤成骨细胞(K7M2-WT)模型评价其体外抗骨肉瘤活性.结果:BPNSs的PEG表面修饰提高了其生物稳定性,并减缓了氧化降解速度;BPNSs的载药率和包封率分别为(101.6±3.2)％和(25.3±0.9)％;基于BPNSs的智能NIR响应复合水凝胶在37 ℃下能够快速完成溶胶-凝胶相变,形成半固体药物储存库,并具有良好的通针性,优异的光热转换性能,pH/NIR智能响应的药物释放性能,良好的体外生物相容性和体外光热-化疗协同抗骨肉瘤效果.结论:基于BPNSs的智能NIR响应复合水凝胶的制备过程简单可控,可通过NIR诱导实现智能光控和持续释药,使骨肉瘤的光热-化疗协同治疗更加高效,在原位骨肉瘤等浅表肿瘤的治疗中具有广阔的应用前景.
Abstract
OBJECTIVE To prepare smart near-infrared light(NIR)-responsive composite hydrogels based upon black phosphorus nanosheets(BPNSs)for synergistic anti-osteosarcoma photothermal-chemotherapy.METHODS BPNSs were pre-pared by liquid phase exfoliation and modified with polyethylene glycol diamine[PEG-(NH2)2]as a modifier under the principle of electrostatic interaction.And modified BPNSs were loaded efficiently with adriamycin(DOX)by electrostatic interaction.BPNSs modified by PEG and loaded with DOX were co-blended in sodium alginate/poroxam composite hydrogel matrix for pre-paring smart NIR light responsive composite hydrogels based upon BPNSs by cold method.And in vitro anti-osteosarcoma potency was evaluated by a murine model of osteosarcoma osteoblast(K7M2-WT).RESULTS PEG surface modification of BPNSs improved biostability and slowed down oxidative degradation;drug loading and encapsulation rates of BPNSs were(101.6±3.2)％and(25.3±0.9)％respectively;smart NIR photoresponsive composite hydrogel based upon BPNSs could rap-idly complete sol-gel phase transition at 37 ℃ to form a semi-solid drug reservoir with decent through-needle property,excellent photothermal conversion,pH/NIR smart response drug release performance,excellent in vitro biocompatibility and in vitro syner gistic anti-osteosarcoma photothermal-chemotherapy.CONCLUSION The preparation process of intelligent NIR photorespon-sive composite hydrogels based upon BPNSs is both simple and controllable.It may achieve intelligent photocontrol and sustained drug release through NIR induction,making synergistic in situ anti-osteosarcoma photothermal-chemotherapy more efficient and promising.
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