材料科学
癌症治疗
利基
癌症
纳米技术
生物医学工程
医学
生物
内科学
生态学
作者
Yiliang Yang,Peng Yan,Yitian Du,Lin Meng,Jiajia Li,Datong Gao,Zhenzhen Yang,Sheng Wang,Yanxia Zhou,Xinru Li,Taiqiang Yan,Xian Qi
出处
期刊:Biomaterials
[Elsevier]
日期:2024-04-01
卷期号:: 122581-122581
标识
DOI:10.1016/j.biomaterials.2024.122581
摘要
Cancer stem cells (CSCs) characterized by self-renewal, invasiveness, tumorigenicity and resistance to treatment are regarded as the thorniest issues in refractory tumors. We develop a targeted and hierarchical controlled release nano-therapeutic platform (SEED-NPs) that self-identifies and responds to CSC and non-CSC micro-niches of tumors. In non-CSC micro-niche, reactive oxygen species (ROS) trigger the burst release of the chemotherapeutic drug and photosensitizer to kill tumor cells and reduce tumor volume by combining chemotherapy and photodynamic therapy (PDT). In CSC micro-niche, the preferentially released differentiation drug induces CSC differentiation and transforms CSCs into chemotherapy-sensitive cells. SEED-NPs exhibit an extraordinary capacity for downregulating the stemness of CD44+/CD24- SP (side population) cell population both in vitro and in vivo, and reveal a 4-fold increase of tumor-targeted accumulation. Also, PDT-generated ROS promote the formation of tunneling nanotubes and facilitate the divergent network transport of drugs in deep tumors. Moreover, ROS in turn promotes CSC differentiation and drug release. This positive-feedback-loop strategy enhances the elimination of refractory CSCs. As a result, SEED-NPs achieve excellent therapeutic effects in both 4T1 SP tumor-bearing mice and regular 4T1 tumor-bearing mice without obvious toxicities and eradicate half of mice tumors. SEED-NPs integrate differentiation, chemotherapy and PDT, which proved feasible and valuable, indicating that active targeting and hierarchical release are necessary to enhance antitumor efficacy. These findings provide promising prospects for overcoming barriers in the treatment of CSCs.
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