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阿霉素-三价铁-血竭素无限配位聚合物@PDA:CuO 复合纳米粒子用于具有成本效益的程序光热-化学动力学协同双重药物化疗三联增效肿瘤治疗。

Doxorubicin-Fe(III)-Gossypol Infinite Coordination Polymer@PDA:CuO Composite Nanoparticles for Cost-Effective Programmed Photothermal-Chemodynamic-Coordinated Dual Drug Chemotherapy Trimodal Synergistic Tumor Therapy.

机构信息

Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China.

Xi'an Key Laboratory for Prevention and Treatment of Common Aging Diseases, Translational and Research Centre for Prevention and Therapy of Chronic Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an 710021, PR China.

出版信息

ACS Nano. 2023 Jul 11;17(13):12544-12562. doi: 10.1021/acsnano.3c02401. Epub 2023 Jun 24.

DOI:10.1021/acsnano.3c02401
PMID:37354436
Abstract

To achieve the maximum therapeutic effects and minimize adverse effects of trimodal synergistic tumor therapies, a cost-effective programmed photothermal (PTT)-chemodynamic (CDT)-coordinated dual drug chemotherapy (CT) trimodal synergistic therapy strategy in chronological order is proposed. According to the status or volumes of the tumors, the intensity and time of each therapeutic modality are optimized, and three modalities are combined programmatically and work in chronological order. The optimal synergistic therapy begins with high-intensity PTT for 10 min to ablate larger tumors, followed by medium-intensity CDT for several hours to eliminate medium-sized tumors, and then low-intensity coordinated dual drugs CT lasts over 48 h to clear smaller residual tumors. Composite nanoparticles, made of Fe-coordinated polydopamine mixed with copper peroxide as the cores and their surface dotted with lots of doxorubicin-Fe(III)-gossypol infinite coordination polymers (ICPs), have been developed to implement the strategy. These composite nanoparticles show excellent synergistic effects with the minimum dose of therapeutic agents and result in nearly 100% tumor inhibition for mice bearing PC-3 tumors and no observed recurrence within 60 days of treatment. The ratios of the different therapeutic agents in the composite nanoparticles can be adjusted to accommodate different types of tumors with this cost-effective programmed trimodal therapy strategy.

摘要

为了实现三模态协同肿瘤治疗的最大治疗效果和最小不良反应,我们提出了一种具有成本效益的定时程序光热(PTT)-化学动力学(CDT)-协调双重药物化疗(CT)三模态协同治疗策略。根据肿瘤的状态或体积,优化每种治疗模式的强度和时间,并定时、程序化地将三种模式结合起来。最佳协同治疗从 10 分钟的高强度 PTT 开始,以消融较大的肿瘤,然后进行数小时的中强度 CDT 以消除中等大小的肿瘤,最后进行低强度协调双重药物 CT 持续超过 48 小时以清除较小的残留肿瘤。我们开发了由铁配位聚多巴胺与过氧化铜混合作为核心,并在其表面点缀大量阿霉素-Fe(III)-棉酚无限配位聚合物(ICPs)的复合纳米粒子来实施该策略。这些复合纳米粒子表现出优异的协同作用,以最小的治疗剂剂量导致携带 PC-3 肿瘤的小鼠的肿瘤几乎完全抑制,并且在治疗后 60 天内没有观察到复发。通过这种具有成本效益的定时程序三模态治疗策略,可以调整复合纳米粒子中不同治疗剂的比例,以适应不同类型的肿瘤。

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