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Photosensitive Nanoparticles Combining Vascular‐Independent Intratumor Distribution and On‐Demand Oxygen‐Depot Delivery for Enhanced Cancer Photodynamic Therapy
Small ( IF 13.0 ) Pub Date : 2018-02-06 , DOI: 10.1002/smll.201703045 Caiyan Zhao 1, 2 , Yujia Tong 1 , Xianlei Li 1, 2 , Leihou Shao 1, 2 , Long Chen 1, 2 , Jianqing Lu 1 , Xiongwei Deng 1 , Xuan Wang 1, 2 , Yan Wu 1, 2
Small ( IF 13.0 ) Pub Date : 2018-02-06 , DOI: 10.1002/smll.201703045 Caiyan Zhao 1, 2 , Yujia Tong 1 , Xianlei Li 1, 2 , Leihou Shao 1, 2 , Long Chen 1, 2 , Jianqing Lu 1 , Xiongwei Deng 1 , Xuan Wang 1, 2 , Yan Wu 1, 2
Affiliation
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In drug delivery, the poor tumor perfusion results in disappointing therapeutic efficacy. Nanomedicines for photodynamic therapy (PDT) greatly need deep tumor penetration due to short lifespan and weak diffusion of the cytotoxic reactive oxygen species (ROS). The damage of only shallow cells can easily cause invasiveness and metastasis. Moreover, even if the nanomedicines enter into deeper lesion, the effectiveness of PDT is limited due to the hypoxic microenvironment. Here, a deep penetrating and oxygen self‐sufficient PDT nanoparticle is developed for balanced ROS distribution within tumor and efficient cancer therapy. The designed nanoparticles (CNPs/IP) are doubly emulsified (W/O/W) from poly(ethylene glycol)‐poly(ε‐caprolactone) copolymers doped with photosensitizer IR780 in the O layer and oxygen depot perfluorooctyl bromide (PFOB) inside the core, and functionalized with the tumor penetrating peptide Cys‐Arg‐Gly‐Asp‐Lys (CRGDK). The CRGDK modification significantly improves penetration depth of CNPs/IP and makes the CNPs/IP arrive at both the periphery and hypoxic interior of tumors where the PFOB releases oxygen, effectively alleviating hypoxia and guaranteeing efficient PDT performance. The improved intratumoral distribution of photosensitizer and adequate oxygen supply augment the sensitivity of tumor cells to PDT and significantly improve PDT efficiency. Such a nanosystem provides a potential platform for improved therapeutic index in anticancer therapy.
中文翻译：
光敏性纳米粒子结合了独立于血管内的肿瘤内分布和按需供氧库的递送方式，从而增强了癌症的光动力疗法
在药物递送中，不良的肿瘤灌注导致令人失望的治疗效果。由于生命周期短和细胞毒性活性氧（ROS）的扩散较弱，用于光动力疗法（PDT）的纳米药物非常需要深层肿瘤渗透。仅浅层细胞的损伤很容易引起侵袭和转移。而且，即使纳米药物进入更深的病灶，由于缺氧的微环境，PDT的有效性也受到限制。在这里，开发了一种深层渗透和氧自给自足的PDT纳米颗粒，用于平衡ROS在肿瘤内的分布和有效的癌症治疗。设计的纳米粒子（CNPs / IP）由O层中掺杂有光敏剂IR780的聚（乙二醇）-聚（ε-己内酯）共聚物和内部的氧仓库全氟辛基溴化物（PFOB）双重乳化（W / O / W）。核心，并与肿瘤穿透肽Cys-Arg-Gly-Asp-Lys（CRGDK）一起功能化。CRGDK修饰显着提高了CNPs / IP的穿透深度，并使CNPs / IP到达PFOB释放氧气的肿瘤的外围和低氧内部，有效缓解了低氧状态并确保了有效的PDT性能。光敏剂在肿瘤内分布的改善和充足的氧气供应增强了肿瘤细胞对PDT的敏感性，并显着提高了PDT的效率。
更新日期：2018-02-06
中文翻译：
光敏性纳米粒子结合了独立于血管内的肿瘤内分布和按需供氧库的递送方式，从而增强了癌症的光动力疗法
在药物递送中，不良的肿瘤灌注导致令人失望的治疗效果。由于生命周期短和细胞毒性活性氧（ROS）的扩散较弱，用于光动力疗法（PDT）的纳米药物非常需要深层肿瘤渗透。仅浅层细胞的损伤很容易引起侵袭和转移。而且，即使纳米药物进入更深的病灶，由于缺氧的微环境，PDT的有效性也受到限制。在这里，开发了一种深层渗透和氧自给自足的PDT纳米颗粒，用于平衡ROS在肿瘤内的分布和有效的癌症治疗。设计的纳米粒子（CNPs / IP）由O层中掺杂有光敏剂IR780的聚（乙二醇）-聚（ε-己内酯）共聚物和内部的氧仓库全氟辛基溴化物（PFOB）双重乳化（W / O / W）。核心，并与肿瘤穿透肽Cys-Arg-Gly-Asp-Lys（CRGDK）一起功能化。CRGDK修饰显着提高了CNPs / IP的穿透深度，并使CNPs / IP到达PFOB释放氧气的肿瘤的外围和低氧内部，有效缓解了低氧状态并确保了有效的PDT性能。光敏剂在肿瘤内分布的改善和充足的氧气供应增强了肿瘤细胞对PDT的敏感性，并显着提高了PDT的效率。
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