Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, PR China.
School of Medical Devices, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, PR China.
Acta Biomater. 2022 Aug;148:310-322. doi: 10.1016/j.actbio.2022.06.001. Epub 2022 Jun 5.
Photodynamic therapy (PDT) has been thriving in the theranostics of cancer in recent years. However, due to a series of problems such as high concentration of GSH and insufficient O partial pressure in the tumor micro-environment, it is difficult to achieve the desired therapeutic effects with single PDT. Mesoporous carbon (MC-COOH) has been widely used in photothermal therapy (PTT) due to its high photothermal conversion efficiency and drug loading. In addition, we have discovered that MC-COOH owned high-efficiency glutathione oxidase-like activity for intracellular lasting GSH consumption. Hence, a smart mesoporous carbon nanozyme (CCM) was designed as a dual-GSH depletion agent and O generator combined with PTT to overcome the dilemma of PDT. MnO-doped carbon nanozyme (MC-Mn) was developed as the photothermal vehicles for the efficient loading of photosensitizer (Ce6). Subsequently, 4T1 membrane-coated nanozyme (Ce6/CCM) was constructed to achieve homologous targeting capability. The carbon nanozyme owned the sustained dual-GSH depletion function through MC-COOH and MnO, which greatly destroyed the antioxidant system of the tumor. Meanwhile, MnO could produce affluent O in the presence of HO, thereby alleviating the hypoxic state of tumor tissues and further promoting the generation of ROS. In addition, the novel carbon nanozyme was designed as photoacoustic imaging (PAI) agent and magnetic resonance imaging (MRI) contrast for real-time imaging during tumor therapy. In summary, this work showed that the biomimetic carbon nanozyme could be used as dual-GSH depletion agent and O generator for dual-mode imaging-guided PTT-PDT. STATEMENT OF SIGNIFICANCE: - MC-COOH with highly efficient GSH-OXD activity was first discovered and applied in PDT. - MnO acted as an O generator and GSH depletion agent to enhance PDT. - The tumor-targeting ability of the nanozyme was improved by cell membrane camouflage. - CCM nanozyme possesses both PAI and MRI dual-mode imaging modalities to guide PDT/PTT.
近年来，光动力疗法（PDT）在癌症的治疗中得到了蓬勃发展。然而，由于肿瘤微环境中谷胱甘肽（GSH）浓度高和氧分压不足等一系列问题，单一 PDT 难以达到理想的治疗效果。介孔碳（MC-COOH）由于其高的光热转换效率和药物负载能力，已广泛应用于光热治疗（PTT）。此外，我们发现 MC-COOH 具有高效的谷胱甘肽氧化酶样活性，可用于细胞内持续的 GSH 消耗。因此，设计了一种智能介孔碳纳米酶（CCM）作为联合 PTT 的双重 GSH 耗竭剂和 O 生成剂，以克服 PDT 的困境。MnO 掺杂的碳纳米酶（MC-Mn）被开发为高效负载光敏剂（Ce6）的光热载体。随后，构建了 4T1 膜包覆的纳米酶（Ce6/CCM）以实现同源靶向能力。碳纳米酶通过 MC-COOH 和 MnO 具有持续的双重 GSH 耗竭功能，从而极大地破坏了肿瘤的抗氧化系统。同时，MnO 在 HO 的存在下可以产生丰富的 O，从而缓解肿瘤组织的缺氧状态，并进一步促进 ROS 的产生。此外，该新型碳纳米酶被设计为光声成像（PAI）剂和磁共振成像（MRI）造影剂，用于肿瘤治疗过程中的实时成像。总之，这项工作表明仿生碳纳米酶可作为双重 GSH 耗竭剂和 O 生成剂，用于双模成像引导的 PTT-PDT。
首次发现并应用具有高效 GSH-OXD 活性的 MC-COOH 于 PDT 中。
MnO 作为 O 生成剂和 GSH 耗竭剂增强 PDT。
通过细胞膜伪装提高纳米酶的肿瘤靶向能力。
CCM 纳米酶具有 PAI 和 MRI 双模成像方式，用于指导 PDT/PTT。
