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已发表论文
基于EPR/AT的新型双重策略：通过改善药物递送系统理化性质并调控肿瘤微环境优化治疗效果
Authors Chen L , Deng X , Shen Q, Chen M, Li C, Wang S
Received 21 August 2025
Accepted for publication 9 December 2025
Published 15 January 2026 Volume 2026:21 559763
DOI https://doi.org/10.2147/IJN.S559763
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. RDK Misra
Long Chen,1,2,* Xiang Deng,1– 3,* Qian Shen,1– 3 Min Chen,4 Churong Li,2,5 Shunxi Wang1,2,6,7
1The Second Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital Chengdu, Sichuan, 610000, People’s Republic of China; 2Non-Coding RNA and Drug Discovery Key Laboratory of Sichuan Province, School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan, 610550, People’s Republic of China; 3Clinical Medical College, Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of China; 4Department of Dermatology, Nanbu People’s Hospital, Nanchong, Sichuan, 637300, People’s Republic of China; 5Radiotherapy Center, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, 610041, People’s Republic of China; 6Institute of Pathology & Southwest Cancer Center, the First Afliated Hospital (Southwest Hospital) of Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China; 7Chongqing Institute of Advanced Pathology, Jinfeng Laboratory, Chongqing, 400039, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Churong Li, Email mylcr2009@163.com Shunxi Wang, Email sx_wang1024@126.com
摘要：肿瘤纳米药物的临床应用进展正因其在肿瘤部位的有限蓄积而严重受阻，这也是纳米药物在临床试验中屡屡失败的关键原因。此类药物的疗效与其给药途径密切相关，无论是口服、透皮、静脉还是脑内给药，每条路径都面临独特的生理屏障，阻碍了药物的生物利用度和精准肿瘤靶向。导致蓄积不足的主要原因包括：单核吞噬细胞系统的快速清除、伴随蛋白质冠形成的调理作用、肾滤过作用，以及肿瘤血管异常且异质性的特点，这些因素限制了通过增强渗透与滞留效应实现的被动靶向效率。为此，主动靶向策略被广泛探索，包括在纳米药物表面修饰配体、抗体或适体，以特异性结合癌细胞或血管上过度表达的受体。尽管付出了诸多努力，诸如致密的细胞外基质、升高的间质流体压力，以及动物模型与人类患者之间增强渗透与滞留效应的显著差异等挑战，仍然限制了治疗药物的渗透深度。本综述系统阐述了纳米药物的递送路径及其蓄积不足的原因，重点探讨了主动靶向以及被动-主动联合策略在提升肿瘤特异性递送方面的潜力。通过精密的纳米设计克服这些生物屏障，对于开发具有更高肿瘤蓄积和更佳疗效的下一代纳米药物至关重要。
1The Second Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital Chengdu, Sichuan, 610000, People’s Republic of China; 2Non-Coding RNA and Drug Discovery Key Laboratory of Sichuan Province, School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan, 610550, People’s Republic of China; 3Clinical Medical College, Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of China; 4Department of Dermatology, Nanbu People’s Hospital, Nanchong, Sichuan, 637300, People’s Republic of China; 5Radiotherapy Center, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, 610041, People’s Republic of China; 6Institute of Pathology & Southwest Cancer Center, the First Afliated Hospital (Southwest Hospital) of Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China; 7Chongqing Institute of Advanced Pathology, Jinfeng Laboratory, Chongqing, 400039, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Churong Li, Email mylcr2009@163.com Shunxi Wang, Email sx_wang1024@126.com
摘要：肿瘤纳米药物的临床应用进展正因其在肿瘤部位的有限蓄积而严重受阻，这也是纳米药物在临床试验中屡屡失败的关键原因。此类药物的疗效与其给药途径密切相关，无论是口服、透皮、静脉还是脑内给药，每条路径都面临独特的生理屏障，阻碍了药物的生物利用度和精准肿瘤靶向。导致蓄积不足的主要原因包括：单核吞噬细胞系统的快速清除、伴随蛋白质冠形成的调理作用、肾滤过作用，以及肿瘤血管异常且异质性的特点，这些因素限制了通过增强渗透与滞留效应实现的被动靶向效率。为此，主动靶向策略被广泛探索，包括在纳米药物表面修饰配体、抗体或适体，以特异性结合癌细胞或血管上过度表达的受体。尽管付出了诸多努力，诸如致密的细胞外基质、升高的间质流体压力，以及动物模型与人类患者之间增强渗透与滞留效应的显著差异等挑战，仍然限制了治疗药物的渗透深度。本综述系统阐述了纳米药物的递送路径及其蓄积不足的原因，重点探讨了主动靶向以及被动-主动联合策略在提升肿瘤特异性递送方面的潜力。通过精密的纳米设计克服这些生物屏障，对于开发具有更高肿瘤蓄积和更佳疗效的下一代纳米药物至关重要。