Nanoscale Metal–Organic Framework Confines Zinc-Phthalocyanine Photosensitizers for Enhanced Photodynamic Therapy

The performance of photodynamic therapy (PDT) depends on the solubility, pharmacokinetic behaviors, and photophysical properties of photosensitizers (PSs). However, highly conjugated PSs with strong reactive oxygen species (ROS) generation efficiency tend to have poor solubility and aggregate in aqueous environments, leading to suboptimal PDT performance. Here, we report a new strategy to load highly conjugated but poorly soluble zinc-phthalocyanine (ZnP) PSs in the pores of a Hf12-QC (QC = 2″,3′-dinitro-[1,1’:4′,1”;4″,1’”-quaterphenyl]-4,4’”-dicarboxylate) nanoscale metal–organic framework to afford ZnP@Hf-QC with spatially confined ZnP PSs. ZnP@Hf-QC avoids aggregation-induced quenching of ZnP excited states to significantly enhance ROS generation upon light irradiation. With higher cellular uptake, enhanced ROS generation, and better biocompatibility, ZnP@Hf-QC mediated PDT exhibited an IC50 of 0.14 μM and achieved exceptional antitumor efficacy with >99% tumor growth inhibition and 80% cure rates on two murine colon cancer models.

[1]  Wei Pan,et al.  Metal-Organic Frameworks-Based Antitumor Agents. , 2021, Angewandte Chemie.

[2]  Zhenhua Sun,et al.  Nanoscale metal–organic framework composites for phototherapy and synergistic therapy of cancer , 2021 .

[3]  Wenbin Lin,et al.  Supramolecular metal-based nanoparticles for drug delivery and cancer therapy. , 2021, Current opinion in chemical biology.

[4]  Jiangli Fan,et al.  Recent progress in photosensitizers for overcoming the challenges of photodynamic therapy: from molecular design to application. , 2021, Chemical Society reviews.

[5]  Wenbin Lin,et al.  Nanoscale Metal-Organic Layer Isolates Phthalocyanines for Efficient Mitochondria-Targeted Photodynamic Therapy. , 2021, Journal of the American Chemical Society.

[6]  J. Lei,et al.  Multifunctional metal-organic framework heterostructures for enhanced cancer therapy. , 2020, Chemical Society reviews.

[7]  Yue‐Biao Zhang,et al.  Anisotropic reticular chemistry , 2020, Nature Reviews Materials.

[8]  Qizhi Zhang,et al.  Porphyrin‐Based Metal−Organic Framework Compounds as Promising Nanomedicines in Photodynamic Therapy , 2020, ChemMedChem.

[9]  Xiaoyuan Chen,et al.  Clinical development and potential of photothermal and photodynamic therapies for cancer , 2020, Nature Reviews Clinical Oncology.

[10]  J. Kollár,et al.  Cationic versus Anionic Phthalocyanines for Photodynamic Therapy: What a Difference the Charge Makes. , 2020, Journal of medicinal chemistry.

[11]  Xiaoyuan Chen,et al.  Dancing with reactive oxygen species generation and elimination in nanotheranostics for disease treatment. , 2020, Advanced drug delivery reviews.

[12]  Wenbin Lin,et al.  Nanoscale Metal-Organic Frameworks Stabilize Bacteriochlorins for Type I and Type II Photodynamic Therapy. , 2020, Journal of the American Chemical Society.

[13]  Lei Wang,et al.  Metal–Organic Frameworks for Photodynamic Therapy: Emerging Synergistic Cancer Therapy , 2020, Biotechnology journal.

[14]  R. Pandey,et al.  The unique features and promises of phthalocyanines as advanced photosensitisers for photodynamic therapy of cancer. , 2019, Chemical Society reviews.

[15]  Michael R Hamblin,et al.  Photodynamic Therapy for Cancer: What's Past is Prologue , 2019, Photochemistry and photobiology.

[16]  C. van Nostrum,et al.  Amphiphilic phthalocyanines in polymeric micelles: a supramolecular approach toward efficient third-generation photosensitizers. , 2019, Journal of materials chemistry. B.

[17]  Wei Pan,et al.  Programmed Release of Dihydroartemisinin for Synergistic Cancer Therapy with CaCO₃ Mineralized Metal-Organic Framework. , 2019, Angewandte Chemie.

[18]  M. C. García Vior,et al.  ZINC(II) PHTHALOCYANINES AS PHOTOSENSITIZERS FOR ANTITUMOR PHOTODYNAMIC THERAPY. , 2019, The international journal of biochemistry & cell biology.

[19]  Wei Pan,et al.  Programmed Release of Dihydroartemisinin for Synergistic Cancer Therapy Using a CaCO 3 Mineralized Metal–Organic Framework , 2019, Angewandte Chemie.

[20]  J. Lovell,et al.  Liposomal formulations of photosensitizers. , 2019, Biomaterials.

[21]  Bin Liu,et al.  Cancer-Cell-Activated Photodynamic Therapy Assisted by Cu(II) Based Metal-Organic Framework. , 2019, ACS nano.

[22]  Shuang Liang,et al.  Monodispersed Copper(I)‐Based Nano Metal–Organic Framework as a Biodegradable Drug Carrier with Enhanced Photodynamic Therapy Efficacy , 2019, Advanced science.

[23]  E. Sergeeva,et al.  Photobiological properties of phthalocyanine photosensitizers Photosens, Holosens and Phthalosens: A comparative in vitro analysis. , 2019, Journal of photochemistry and photobiology. B, Biology.

[24]  Jin‐Yue Zeng,et al.  Metal‐Organic Framework Mediated Multifunctional Nanoplatforms for Cancer Therapy , 2018, Advanced Therapeutics.

[25]  J. Ortega,et al.  Binding of an amphiphilic phthalocyanine to pre-formed liposomes confers light-triggered cargo release. , 2018, Journal of materials chemistry. B.

[26]  Pui-Chi Lo,et al.  Polymeric micelles encapsulating pH‐responsive doxorubicin prodrug and glutathione‐activated zinc(II) phthalocyanine for combined chemotherapy and photodynamic therapy , 2018, Journal of controlled release : official journal of the Controlled Release Society.

[27]  Jian Zhu,et al.  Zinc phthalocyanine encapsulated in polymer micelles as a potent photosensitizer for the photodynamic therapy of osteosarcoma. , 2018, Nanomedicine : nanotechnology, biology, and medicine.

[28]  Xian‐Zheng Zhang,et al.  π-Extended Benzoporphyrin-Based Metal-Organic Framework for Inhibition of Tumor Metastasis. , 2018, ACS nano.

[29]  Wenbo Wu,et al.  Metal–Organic Framework as a Simple and General Inert Nanocarrier for Photosensitizers to Implement Activatable Photodynamic Therapy , 2018 .

[30]  Wenbin Lin,et al.  Nanoscale Metal-Organic Frameworks for Phototherapy of Cancer. , 2017, Coordination chemistry reviews.

[31]  Ruihan Dai,et al.  Electron Crystallography Reveals Atomic Structures of Metal-Organic Nanoplates with M12(μ3-O)8(μ3-OH)8(μ2-OH)6 (M = Zr, Hf) Secondary Building Units. , 2017, Inorganic chemistry.

[32]  Z. Yamani,et al.  Multivariate metal-organic frameworks , 2017 .

[33]  S. Wuttke,et al.  Metal‐Organic Framework Nanoparticles in Photodynamic Therapy: Current Status and Perspectives , 2017 .

[34]  Lei Wang,et al.  Metal–Organic Framework@Porous Organic Polymer Nanocomposite for Photodynamic Therapy , 2017 .

[35]  Ian D. McGilvray,et al.  Nanoparticle-liver interactions: Cellular uptake and hepatobiliary elimination. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[36]  Tayyaba Hasan,et al.  Beyond the Barriers of Light Penetration: Strategies, Perspectives and Possibilities for Photodynamic Therapy , 2016, Theranostics.

[37]  Jihye Park,et al.  Size-Controlled Synthesis of Porphyrinic Metal-Organic Framework and Functionalization for Targeted Photodynamic Therapy. , 2016, Journal of the American Chemical Society.

[38]  Radim Kučera,et al.  Far-red-absorbing cationic phthalocyanine photosensitizers: synthesis and evaluation of the photodynamic anticancer activity and the mode of cell death induction. , 2015, Journal of medicinal chemistry.

[39]  K. Soo,et al.  Nanoparticles in photodynamic therapy. , 2015, Chemical reviews.

[40]  Ick Chan Kwon,et al.  Nanophotosensitizers toward advanced photodynamic therapy of Cancer. , 2013, Cancer letters.

[41]  Abhishek D. Garg,et al.  Immunogenic cell death and DAMPs in cancer therapy , 2012, Nature Reviews Cancer.

[42]  Demin Liu,et al.  Nanoscale metal-organic frameworks for biomedical imaging and drug delivery. , 2011, Accounts of chemical research.

[43]  Tebello Nyokong,et al.  Synthetic pathways to water-soluble phthalocyanines and close analogs , 2010 .

[44]  Jinatta Jittiwat,et al.  Biodistribution of gold nanoparticles and gene expression changes in the liver and spleen after intravenous administration in rats. , 2010, Biomaterials.

[45]  Gang Zheng,et al.  Activatable photosensitizers for imaging and therapy. , 2010, Chemical reviews.

[46]  Michael R Hamblin,et al.  Photodynamic therapy and anti-tumour immunity , 2006, Nature Reviews Cancer.

[47]  S. Gibson,et al.  Current clinical and preclinical photosensitizers for use in photodynamic therapy. , 2004, Journal of medicinal chemistry.

[48]  Cornelus F. van Nostrum,et al.  Polymeric micelles to deliver photosensitizers for photodynamic therapy. , 2004 .

[49]  H. Ogata,et al.  Effect of peripheral substitution on the electronic absorption and fluorescence spectra of metal-free and zinc phthalocyanines. , 2003, Chemistry.

[50]  C. van Nostrum.  Polymeric micelles to deliver photosensitizers for photodynamic therapy. , 2004, Advanced drug delivery reviews.

[51]  Zhuang Liu,et al.  Antitumor Agents Based on Metal–Organic Frameworks , 2022, Angewandte Chemie.