功能高分子引发生物矿化实现肿瘤阻断治疗  

Functional Polymer-Initiating Biomineralization for Tumor Blockade Therapy

作　　者：刘洋[1,2] 庄雅灵[1,2] 丁建勋 LIU Yang;ZHUANG Yaling;DING Jianxun(Key Laboratory of Polymer Ecomaterials,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China;School of Applied Chemistry and Engineering,University of Science and Technology of China,Hefei 230026,China)

机构地区：[1]中国科学院长春应用化学研究所,生态环境高分子材料重点实验室,长春130022 [2]中国科学技术大学应用化学与工程学院,合肥230026

出　　处：《功能高分子学报》2023年第1期1-5,共5页Journal of Functional Polymers

基　　金：国家自然科学基金(52273158,U21A2099,52022095,52073280,51973216,51873207,51833010);吉林省科技发展计划(20210509005RQ,20210504001GH,20200404182YY)。

摘　　要：作为一种不依赖于肿瘤组织渗透的治疗策略,阻断疗法通过阻碍肿瘤与周围微环境之间的物质交换而有效抑制肿瘤的生长和转移。然而,血管阻断、细胞外基质构建等手段存在系统毒性大、肿瘤杀伤不完全、有效持续时间短等问题。受生物体矿化过程的启发,在肿瘤周围构筑生物矿化层成为一种新兴、安全、有效且持久的肿瘤阻断治疗创新模式。基于此,本研究团队首先将阿仑膦酸钠(ALN)键合到1,2-二硬脂酰基-sn-甘油-3-磷酸乙醇胺-N-聚乙二醇-琥珀酰亚胺酯(DSPE-PEG-NHS)的末端,合成了功能高分子DSPE-PEG-ALN。其中,DSPE端可以插入到细胞膜上,另一端的双膦酸可以高效吸附环境中的钙离子等阳离子而引发矿物沉积的连锁反应,在肿瘤周围形成生物矿化层,阻断肿瘤进展。为了进一步提高矿化策略的选择性,我们设计并合成了肿瘤酸度触发的引发生物矿化的聚氨基酸纳米粒子(BINP)。在中性条件下,BINP上的长烷基链组装在纳米粒子的内部,而在肿瘤组织的弱酸性环境中暴露,实现肿瘤细胞膜的特异性插入,原位引发生物矿化,选择性阻断肿瘤进展。原位引发生物矿化功能高分子的设计和应用为肿瘤阻断治疗提供了具有临床应用前景的创新思路。Tumor blockade therapy is a promising penetration-independent antitumor modality through inhibiting the substance exchange between the tumor and surrounding microenvironments.However,the strategies of vessel-targeted blockade,construction of an artificial extracellular matrix,and so forth are limited by possible side effects,inadequate tumor obstruction,and short duration.Inspired by the biomineralization in living organisms,artificially induced biomineralization in the tumor tissues has been emerging as an unconventional therapeutic modality characterized by long duration and satisfying biocompatibility.On this basis,our group reacted alendronate(ALN)with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-poly(ethylene glycol)-hydroxysuccinimide eater(DSPE-PEG-NHS)to synthesize DSPE-PEG-ALN,in which the DSPE group was able to insert into cytomembrane,and bisphosphonic group attracted positive ions,mainly calcium ion,to initiate the chain reaction of biomineral deposition.Ultimately,an intense physical barrier was constructed in the periphery of tumor tissue,leading to effective tumor inhibition.To realize selective biomineralization around the tumor tissue,we designed a polypeptide-based biomineralization-inducing nanoparticle(BINP)equipped with the tumor microenvironment-responsiveness.Because of the hydrophobicity of long aliphatic chains,they were assembled in the interior of nanostructures at normal physiological conditions,while tending to expose at acidic microenvironments to selectively insert in the tumor cytomembrane.Then BINP initiated a biomineralized layer right there to achieve effective suppression of osteosarcoma progression.The design and application of in situ biomineralization-inducing functional polymers provide promising alternatives for clinical malignancy therapy.

关 键 词：功能高分子 肿瘤选择性 生物矿化 肿瘤阻断治疗 肿瘤创新治疗 

分 类 号：O633.2[理学—高分子化学]