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一种多功能 cryomicroneedle 贴片,用于可追踪光动力疗法。

A Versatile Cryomicroneedle Patch for Traceable Photodynamic Therapy.

机构信息

Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, China.

Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518055, China.

出版信息

Adv Mater. 2024 Sep;36(36):e2400933. doi: 10.1002/adma.202400933. Epub 2024 Jun 20.

Abstract

Photodynamic therapy (PDT) continues to encounter multifarious hurdles, stemming from the ineffectual preservation and delivery system of photosensitizers, the dearth of imaging navigation, and the antioxidant/hypoxic tumor microenvironment. Herein, a versatile cryomicroneedle patch (denoted as CMN-CCPH) is developed for traceable PDT. The therapeutic efficacy is further amplified by catalase (CAT)-induced oxygen (O) generation and Cu-mediated glutathione (GSH) depletion. The CMN-CCPH is composed of cryomicroneedle (CMN) as the vehicle and CAT-biomineralized copper phosphate nanoflowers (CCP NFs) loaded with hematoporphyrin monomethyl ether (HMME) as the payload. Importantly, the bioactive function of HMME and CAT can be optimally maintained under the protection of CCPH and CMN for a duration surpassing 60 days, leading to bolstered bioavailability and notable enhancements in PDT efficacy. The in vivo visualization of HMME and oxyhemoglobin saturation (sO) monitored by fluorescence (FL)/photoacoustic (PA) duplex real-time imaging unveils the noteworthy implications of CMN-delivered CCPH for intratumoral enrichment of HMME and O with reduced systemic toxicity. This versatile CMN patch demonstrates distinct effectiveness in neoplasm elimination, underscoring its promising clinical prospects.

摘要

光动力疗法(PDT)仍然面临着多种障碍,源于光敏剂的低效保存和递送系统、缺乏成像导航以及抗氧化/缺氧肿瘤微环境。在此,开发了一种多功能 cryomicroneedle 贴片(表示为 CMN-CCPH)用于可追踪的 PDT。通过 CAT 诱导的氧气(O)生成和 Cu 介导的谷胱甘肽(GSH)耗竭,进一步放大了治疗效果。CMN-CCPH 由 cryomicroneedle(CMN)作为载体和负载血卟啉单甲醚(HMME)的 CAT 生物矿化的磷酸铜纳米花(CCP NF)组成。重要的是,在 CCPH 和 CMN 的保护下,HMME 和 CAT 的生物活性功能可以持续超过 60 天,从而提高生物利用度并显著增强 PDT 效果。通过荧光(FL)/光声(PA)双实时成像对 HMME 和氧合血红蛋白饱和度(sO)的体内可视化表明,CMN 递送的 CCPH 对肿瘤内 HMME 和 O 的富集具有重要意义,同时降低了系统毒性。这种多功能 CMN 贴片在消除肿瘤方面表现出明显的效果,突显了其在临床应用中的广阔前景。

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