首都医科大学学报 ›› 2026, Vol. 47 ›› Issue (3): 428-436.doi: 10.3969/j.issn.1006-7795.2026.03.004

• 从分子机制到临床应用:创新药物新突破 • 上一篇    下一篇

基于Pd/Cu-TCPP的光响应纳米体系构建及其协同抗肿瘤机制的初步研究

任奕涵1，2，3，4，5,蒋语嫣1，2，3，4，5,孙琪1，2，3，4，5*   

  1. 1.首都医科大学药学院药剂学系，北京 100069；2.首都医科大学基础-临床联合实验室（儿童肿瘤发病机制与创新药物研究实验室），北京 100069; 3.北京市肽类与小分子药物重点实验室，北京 100069；4.教育部内源性预防工程研究中心，北京 100069；5.北京市生物医学材料实验室，北京 100069
  • 收稿日期:2026-02-02 修回日期:2026-04-09 出版日期:2026-06-21 发布日期:2026-06-26
  • 通讯作者: 孙琪 E-mail:sunqi77@ccmu.edu.cn
  • 基金资助:
    国家自然科学基金项目（82304389），北京市教委科研项目一般项目（KM202310025023），北京市自然科学基金本科生“启研”计划（QY25430）。

Construction of a Pd/Cu-TCPP-based photoresponsive nanosystem and preliminary investigation of its synergistic antitumor mechanism

Ren Yihan1，2，3，4，5, Jiang Yuyan1，2，3，4，5, Sun Qi1，2，3，4，5*   

  1. 1.Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China; 2. Laboratory for Clinical Medicine （Laboratory of Pediatric Tumor Pathogenesis and Innovative Drug Research）, Capital Medical University, Beijing  100069, China；3. Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing 100069, China， 4. Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing 100069,  China; 5.Beijing Laboratory of Biomedical Materials, Beijing 100069, China
  • Received:2026-02-02 Revised:2026-04-09 Online:2026-06-21 Published:2026-06-26
  • Supported by:
    This study was supported by National Natural Science Foundation of China ( 82304389)， Beijing Municipal Education Commission General Research Program (KM202310025023)，Beijing Natural Science Foundation Undergraduate “Qiyan” Research Program (QY25430).

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摘要： 目的  构建基于钯/铜-四（4-羧基苯基）卟啉［Pd/Cu-tetrakis(4-carboxyphenyl)porphyrin，PCT］的光响应纳米递送体系（PCT@PDA/siPKM2），探讨协同光热治疗、氢气治疗与基因治疗的可行性，并初步评价其体外抗肿瘤机制。方法  采用溶剂热法合成PCT纳米粒，通过聚多巴胺（polydopamine, PDA）包覆构建核壳结构，利用聚乙烯亚胺（polyethylenimine, PEI）负载靶向PKM2基因的siRNA（siPKM2），制备PCT@PDA/siPKM2纳米粒。对PCT@PDA/siPKM2纳米粒的理化性质、siRNA负载与保护、光热性能及释氢行为进行表征，并在4T1乳腺癌细胞中评价细胞摄取与抗肿瘤效果。结果  成功构建PCT@PDA/siPKM2纳米体系，纳米颗粒粒径均一、稳定性良好，并具备优异的siRNA负载与保护能力、显著的光热转换与可控释氢性能。体外实验显示该体系可实现溶酶体逃逸，并在激光照射条件下显著抑制4T1细胞活性。结论  成功验证PCT@PDA/siPKM2在光热、释氢与基因干预协同作用中的可行性，为后续协同抗肿瘤研究提供实验基础。

关键词: 金属-卟啉配位, 聚多巴胺, M2型丙酮酸激酶, 小干扰RNA, 光响应纳米材料, 协同抗肿瘤机制

Abstract: Objective  To construct a Pd/Cu-TCPP (PCT)-based photoresponsive nanodelivery system (PCT@PDA/siPKM2), investigate the feasibility of synergistic photothermal therapy, hydrogen therapy, and gene therapy, and preliminarily evaluate its in vitro antitumor mechanism.Methods  PCT nanoparticles were synthesized via a solvothermal method and subsequently coated with polydopamine (PDA) to form a core-shell structure. Polyethylenimine (PEI) was further employed to load siRNA targeting the PKM2 gene (siPKM2), yielding PCT@PDA/siPKM2 nanoparticles. The physicochemical properties, siRNA loading and protection capacity, photothermal performance, and hydrogen release behavior were systematically characterized. Cellular uptake and antitumor efficacy were evaluated in 4T1 mouse breast cancer cell line.Results  Uniform and stable PCT@PDA/siPKM2 nanoparticles were prepared, exhibiting excellent siRNA loading and protection capabilities, as well as prominent photothermal conversion efficiency and controllable hydrogen release under 808 nm near-infrared laser irradiation. In vitro studies demonstrated effective lysosomal escape and significant inhibition of 4T1 cell viability upon laser irradiation.Conclusion  This study confirmed the feasibility of PCT@PDA/siPKM2 in combining photothermal effects, hydrogen release and genetic intervention, providing an experimental basis for further research into synergistic tumour control.

Key words: metal-porphyrin coordination, polydopamine, pyruvate kinase M2, siRNA, photoresponsive nanomaterials, synergistic antitumor mechanism

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