基于黑磷纳米片的智能近红外光响应复合水凝胶的制备及体外抗骨肉瘤活性评价

Preparation of smart near-infrared light-responsive composite hydrogels based on black phosphorus nanosheets and evaluation of in vitro anti-osteosarcoma activity

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-(NH_2)_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,p H/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。

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.