【作者】 杨锋；

【导师】 陈丽华； 温泉；

【作者基本信息】 武汉理工大学 ， 材料工程， 2024， 硕士

【摘要】 癌症治疗一直是医学领域的重大挑战。传统治疗方法存在着诸多局限性。然而,随着时代的发展,新颖治疗手段如免疫疗法、基因治疗和靶向药物治疗等不断涌现,为癌症治疗提供了新的思路和选择。这些治疗方法通常与传统治疗方法联合使用,以提高治疗效果,降低毒副作用,并减少肿瘤复发的可能性。例如,纳米技术与栓塞治疗的联合应用备受关注。通过利用纳米粒子的卓越性能和栓塞治疗的局部治疗效应,可以实现对肿瘤的精准治疗和有效控制。因此,建立一个联合治疗肿瘤的策略是非常有意义的。本研究设计了一种金纳米颗粒联合聚氨基酸型栓塞的复合材料。金纳米颗粒作为荧光示踪剂,实现对肿瘤位置的定位和监测;聚氨基酸栓塞可有效阻断肿瘤养分提供,实现局部治疗。这种复合材料具备定位诊疗一体化优势,同时兼具栓塞治疗效果。首先,我们利用甲氧基聚乙二醇胺（mPEG-NH₂）引发了不同比例的Bn-L-Glu-NCA和L-Tyr-NCA,合成了聚合物mPEG-PLGTs,然后与L-半胱氨酸改性的金纳米颗粒（AuNPs）进行了静电复合,得到了复合材料AuNPs@（mPEG-PLGTs）。接着,我们进行了一系列理化性能的表征,证实了复合材料具有良好的荧光性能和特定pH响应能力。其次,我们进行了体外评价,验证了该复合材料的生物相容性、降解性和稳定性。最后,我们在BALB/c-nu裸鼠上建立了肿瘤模型,评估了复合材料的治疗效果。实验结果表明,在复合材料作用后,肿瘤在第一次注射后的第四天开始有所缩小,20天后肿瘤明显萎缩,成功抑制了肿瘤生长,展现出良好的抗肿瘤效果。同时,通过近红外活体成像技术,我们观察到复合材料在BALB/c-nu裸鼠体内具有良好的荧光示踪性能。综上所述,我们成功开发了一个优秀的复合材料。该复合材料不仅高效进行栓塞治疗,还能够实现了对肿瘤位置的准确定位。更多还原

【Abstract】 Cancer treatment has long been a formidable challenge in the medical field.Traditional treatment modalities are fraught with limitations.However,with the passage of time,novel approaches such as immunotherapy,gene therapy,and targeted drug therapy have emerged,offering new avenues for tackling cancer.These innovative methods,often used in conjunction with conventional treatments,aim to enhance efficacy,minimize toxicity,and reduce the likelihood of tumor recurrence.One notable approach garnering attention is the combined application of nanotechnology and embolization therapy.By leveraging the remarkable properties of nanoparticles alongside the localized therapeutic effects of embolization,precise tumor treatment and effective tumor control can be achieved.Consequently,developing a strategy for combined tumor therapy holds significant promise.In this study,we devised a composite material that combines gold nanoparticles with amino acid-based embolization.Gold nanoparticles serve as fluorescent tracers for tumor localization and monitoring,while amino acid-based embolization effectively disrupts tumor nutrient supply,facilitating localized treatment.This composite material offers the advantage of integrated diagnosis and precise treatment localization,while also delivering the therapeutic effects of embolization.To begin,we synthesized the polymer mPEG-PLGTs by initiating polymerization with different ratios of Bn-L-Glu-NCA and L-Tyr-NCA using methoxy polyethylene glycol amine（mPEG-NH₂）.Subsequently,we electrostatically complexed this polymer with L-cysteine-modified gold nanoparticles（AuNPs）to obtain the composite material AuNPs@（mPEG-PLGTs）.A comprehensive series of physicochemical characterizations confirmed the excellent fluorescence performance and specific pH-responsive capability of the composite material.Following this,we conducted in vitro evaluations to verify its biocompatibility,degradability,and stability.Finally,we established a tumor model in BALB/c-nu nude mice to assess the therapeutic efficacy of the composite material.Our experimental findings demonstrated that following administration of the composite material,tumors began to shrink by the fourth day after the initial injection.After a treatment period of 20days,tumors exhibited significant regression,effectively inhibiting tumor growth and showcasing promising anti-tumor effects.Additionally,through near-infrared in vivo imaging,we observed that the composite material exhibited excellent fluorescence tracking performance in BALB/c-nu nude mice.In conclusion,we have successfully developed an outstanding composite material.This composite material not only facilitates efficient embolization therapy but also enables precise localization of tumor sites,holding great potential for advancing cancer treatment strategies.更多还原