Oxygen Self-Sufficient Core–Shell Metal–Organic Framework-Based Smart Nanoplatform for Enhanced Synergistic Chemotherapy and Photodynamic Therapy

Abstract

The abnormal angiogenesis and insufficient oxygen supply in solid tumors lead to intratumoral hypoxia, which severely limits the efficacy of traditional photodynamic therapy (PDT). Here, a multifunctional nanoplatform (ZDZP@PP) based on a zeolitic imidazolate framework-67 (ZIF-67) core as a hydrogen peroxide catalyst, a zeolitic imidazolate framework-8 (ZIF-8) shell with a pH-responsive property, and a polydopamine–poly­(ethylene glycol) (PDA–PEG) layer for improving the biocompatibility is fabricated for not only relieving tumor hypoxia but also enhancing the efficacy of combination chemo–photodynamic therapy. The chemotherapy drug doxorubicin (DOX) and photosensitizer protoporphyrin IX (PpIX) are encapsulated in different layers independently; thus, a unique two-stage stepwise release becomes possible. Moreover, the nanoplatform can effectively decompose hydrogen peroxide to produce oxygen and thus relieve tumor hypoxia, which further facilitates the production of cytotoxic reactive oxygen species (ROS) by PpIX under laser irradiation. Both in vitro and in vivo experimental results confirm that the combination chemo–photodynamic therapy with the ZDZP@PP nanoplatform can provide more effective cancer treatment than chemotherapy or PDT alone. Consequently, the oxygen self-sufficient multifunctional nanoplatform holds promising potential to overcome hypoxia and treat solid tumors in the future.

Versatile Nanoscale Metal–Organic Frameworks (nMOFs): An Emerging 3D Nanoplatform for Drug Delivery and Therapeutic Applications

“…Ren and colleagues applied ZIF‐67 as a hydrogen peroxide catalyst and oxygen‐generating agent to sensitize PDT effect for the first time, who designed a multifunctional nanocomposite constructed from DOX‐encapsulated ZIF‐67 core and photosensitizer protoporphyrin IX (PpIX)‐loaded ZIF‐8 shell, followed by PDA−PEG layer coating. [ 108 ] Under the acidic TME, the outer PDA layer and ZIF‐8 shell would decompose to release the loaded PpIX. Subsequently, the ZIF‐67 core enabled to catalyze hydrogen peroxide to generate oxygen, which in turn could alleviate the limitation of tumor hypoxia on PDT, promote PpIX to produce cytotoxic ROS under laser stimulation, and meanwhile trigger the release of DOX, realizing synergistic chemo‐PDT against cancer.…”

Metal-Organic Frameworks and Their Composites Towards Biomedical Applications

“…Compared with monotherapy, which often fails to achieve a desirable therapeutic effect, combination therapies may be more effective. Currently, various combination therapies such as chemotherapy/PDT (Liu et al, 2018;Ren et al, 2020), PDT/ PTT (Gao et al, 2018a;Wang et al, 2019c), PDT/CDT (Wu et al, 2021a), and PDT/immunotherapy (Lan et al, 2018;Cai et al, 2020;Ni et al, 2020) have been increasingly applied. In this way, MOFs deliver different functional agents to kill tumors in different ways.…”

BSA-encapsulated cyclometalated iridium complexes as nano-photosensitizers for photodynamic therapy of tumor cells

“…For example, the nanomaterial is used to carry oxygen to supply raw materials for PDT. [11][12][13][14] For another example, the structure of the photosensitizer is adjusted to increase singlet oxygen quantum yield. [15][16][17][18] Besides, the excitation light is regulated to increase the penetration depth of the light into the tissue for internal tumor treatment.…”