Hypoxia-Triggered Nanoscale Metal–Organic Frameworks for Enhanced Anticancer Activity

Abstract

The oxygen-dependent feature of most photosensitizers (PSs) and the aggravated hypoxia tumor microenvironment seriously impede the photodynamic therapy (PDT) effectiveness. However, this undesirable impediment can be utilized to further trigger the activation of hypoxia-sensitive prodrugs. Moreover, a combined therapy can be used by associating PDT with hypoxia-activated chemotherapy. Herein, a multifunctional Hf-porphyrin nanoscale metal-organic framework (NMOF) platform [Hf/tetra(4-carboxyphenyl)porphine (TCPP)] has been synthesized, with a high porphyrin loading capacity and a well-ordered coordination array preventing porphyrin self-quenching, thus greatly improving the generation efficiency of reactive oxygen species (ROS), which is helpful for PDT. As-synthesized Hf-TCPP nanoparticles possess more than 50 wt % of TCPP PS content, good crystallization, and a large Brunauer-Emmett-Teller surface for further loading the hypoxia-activated prodrug [tirapazamine (TPZ)] in a high-loading content. Additionally, subsequent surface modification with a dopamine-derived polymer (DOPA-PIMA-mPEG) significantly improves their dispersibility and structural stability, and the controlled release kinetics of TPZ. Such a nanoplatform can efficiently produce ROS for PDT upon irradiation, and also the depletion of the oxygen could further aggravate the hypoxic environment of tumors to induce the activation of TPZ for achieving an enhanced treatment efficacy. This work demonstrates the great advantages of an NMOF-based platform in antitumor therapies for combined PDT and hypoxia-activated chemotherapy.

Photodynamic Therapy Based on Nanoscale Metal–Organic Frameworks: From Material Design to Cancer Nanotherapeutics

“…A similar study based on Hf‐TCPP, TPZ, and dopamine‐derived polymer (DOPA‐PIMA‐mPEG) was also reported by Xie et al. in 2018 …”

Porphyrin MOF Dots–Based, Function‐Adaptive Nanoplatform for Enhanced Penetration and Photodynamic Eradication of Bacterial Biofilms

“…The strategy for the synthesis of the function‐adaptive MMNPs was shown in Scheme A. Hf (IV)‐based porphyrin MOFs were first synthesized by a simple solvothermal method according to previous studies . Then a facile ultrasonication treatment was employed to prepare the ultrasmall‐sized pMOF dots.…”

<p>Recent Progress of Nanoscale Metal-Organic Frameworks in Cancer Theranostics and the Challenges of Their Clinical Application</p>

“…86 The realization of combination therapy based on NMOFs relied heavily on their multimodal loading capability. Recently, various types of therapeutic combinations, such as dual chemotherapy drugs, 69 chemotherapy/siRNAs, 68,77 chemotherapy/PDT, 27,32 PDT/ immunotherapy [87][88][89][90] or RT/immunotherapy 91,92 based on NMOFs have been examined for tumor therapies both in vitro and in vivo ( Table 3).…”

“…Several studies demonstrated that combining chemotherapy based on PDT potentially enhanced anticancer efficacy. 27,95 The main obstacle of PDT is the hypoxia of tumor environment, which significantly limits its application. Therefore, relieving tissue hypoxia by NMOFs can be used to enhance the efficacy of PDT.…”

“…Therefore, relieving tissue hypoxia by NMOFs can be used to enhance the efficacy of PDT. Liu et al 27 synthesized TPZ/Hf/TCPP/PEG with high loading capacity of the hypoxia-activated prodrug tirapazamine. This study demonstrated the potential of NMOF-based platforms to combine PDT and chemotherapy.…”