Iron oxide@chlorophyll clustered nanoparticles eliminate bladder cancer by photodynamic immunotherapy-initiated ferroptosis and immunostimulation.
Iron oxide@chlorophyll clustered nanoparticles eliminate bladder cancer by photodynamic immunotherapy-initiated ferroptosis and immunostimulation.
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DOI：
10.1186/s12951-022-01575-7
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发表时间：
2022-08-11
影响因子：
10.2
通讯作者：
Liao, Mei-Yi
中科院分区：
文献类型：
--
作者：
Chin, Yu-Cheng;Yang, Li-Xing;Hsu, Fei-Ting;Hsu, Che-Wei;Chang, Te-Wei;Chen, Hsi-Ying;Chen, Linda Yen-Chien;Chia, Zi Chun;Hung, Chun-Hua;Su, Wu-Chou;Chiu, Yi-Chun;Huang, Chih-Chia;Liao, Mei-Yi
膀胱癌从免疫监视中逃脱导致单一疗法表现出较差的疗效;因此，设计一种多功能纳米颗粒，促进程序性细胞死亡和免疫活化，具有作为治疗策略的潜力。在此，我们开发了一种简单的一锅共沉淀反应，以制备由Fe 3 O 4和铁叶绿素（Chl/Fe）光敏剂组装的簇结构纳米粒子（CNP）。这种纳米组装的CNP，作为一个多功能的治疗诊断剂，可以执行红色-近红外荧光和改变氧化还原平衡的活性氧（ROS）的光诱导和减弱铁介导的脂质过氧化反应诱导的芬顿样反应。经4-羧基苯基硼酸（CPBA）修饰的Fe3O4@Chl/Fe CNP膀胱内滴注可通过BC腔中的糖蛋白靶向BC壁，允许通过光动力疗法（PDT）诱导的单线态氧局部杀伤癌细胞并引起化学动力疗法（CDT）介导的铁凋亡。一种有趣的可能性是在PDT-CDT治疗后肿瘤微环境从免疫抑制性重新编程为免疫刺激性，这通过PD-L1（对效应免疫细胞的较低“关闭”信号）、IDO-1、TGF-β和M2样巨噬细胞的减少以及BC切片上CD 8 + T细胞的诱导来证明。此外，膀胱内灌注Fe3O4@Chl/Fe CNPs可增强BC壁上的大面积分布，提高抗肿瘤疗效，并将存活率从0提高到91.7%。我们的治疗诊断CNP不仅证明了联合PDT-CDT诱导的细胞毒性、ROS产生和铁凋亡有助于治疗效果，而且还为通过同时PDT-CDT消除免疫抑制作用开辟了新的视野。在线版本包含补充材料，可通过10.1186/s12951-022-01575-7获得。
The escape of bladder cancer from immunosurveillance causes monotherapy to exhibit poor efficacy; therefore, designing a multifunctional nanoparticle that boosts programmed cell death and immunoactivation has potential as a treatment strategy. Herein, we developed a facile one-pot coprecipitation reaction to fabricate cluster-structured nanoparticles (CNPs) assembled from Fe3O4 and iron chlorophyll (Chl/Fe) photosensitizers. This nanoassembled CNP, as a multifunctional theranostic agent, could perform red-NIR fluorescence and change the redox balance by the photoinduction of reactive oxygen species (ROS) and attenuate iron-mediated lipid peroxidation by the induction of a Fenton-like reaction. The intravesical instillation of Fe3O4@Chl/Fe CNPs modified with 4-carboxyphenylboronic acid (CPBA) may target the BC wall through glycoproteins in the BC cavity, allowing local killing of cancer cells by photodynamic therapy (PDT)-induced singlet oxygen and causing chemodynamic therapy (CDT)-mediated ferroptosis. An interesting possibility is reprogramming of the tumor microenvironment from immunosuppressive to immunostimulatory after PDT-CDT treatment, which was demonstrated by the reduction of PD-L1 (lower “off” signal to the effector immune cells), IDO-1, TGF-β, and M2-like macrophages and the induction of CD8+ T cells on BC sections. Moreover, the intravesical instillation of Fe3O4@Chl/Fe CNPs may enhance the large-area distribution on the BC wall, improving antitumor efficacy and increasing survival rates from 0 to 91.7%. Our theranostic CNPs not only demonstrated combined PDT-CDT-induced cytotoxicity, ROS production, and ferroptosis to facilitate treatment efficacy but also opened up new horizons for eliminating the immunosuppressive effect by simultaneous PDT-CDT. The online version contains supplementary material available at 10.1186/s12951-022-01575-7.
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影响因子：
12.4
作者：
Blau R;Epshtein Y;Pisarevsky E;Tiram G;Israeli Dangoor S;Yeini E;Krivitsky A;Eldar-Boock A;Ben-Shushan D;Gibori H;Scomparin A;Green O;Ben-Nun Y;Merquiol E;Doron H;Blum G;Erez N;Grossman R;Ram Z;Shabat D;Satchi-Fainaro R
通讯作者：
Satchi-Fainaro R
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
12.4
作者：
Hartmans, Elmire;Tjalma, Jolien J. J.;Nagengast, Wouter B.
通讯作者：
Nagengast, Wouter B.
通过纳米催化剂递送，肿瘤选择性催化纳米医学。
影响因子：
16.6
作者：
Huo M;Wang L;Chen Y;Shi J
通讯作者：
Shi J
影响因子：
14
作者：
Guo, Ranran;Wang, Siqi;Zhang, Peng
通讯作者：
Zhang, Peng