Iridium Complex-Loaded Sorafenib Nanocomposites for Synergistic Chemo-photodynamic Therapy of Hepatocellular Carcinoma

Abstract

Although sorafenib, a multi-kinase inhibitor, has provided noteworthy benefits in patients with hepatocellular carcinoma (HCC), the inevitable side effects, narrow therapeutic window, and low bioavailability seriously affect its clinical application. To be clinically distinctive, innovative drugs must meet the needs of reaching tumor tissues and cause limited side effects to normal organs and tissues. Recently, photodynamic therapy, utilizing a combination of a photosensitizer and light irradiation, was selectively accumulated at the tumor site and taken up effectively via inducing apoptosis or necrosis of cancer cells. In this study, a nano-chemo-phototherapy drug was fabricated to compose an iridium-based photosensitizer combined with sorafenib (IPS) via a self-assembly process. Compared to the free iridium photosensitizer or sorafenib, the IPS exhibited significantly improved therapeutic efficacy against tumor cells because of the increased cellular uptake and the subsequent simultaneous release of sorafenib and generation of reactive oxygen species production upon 532 nm laser irradiation. To evaluate the effect of synergistic treatment, cytotoxicity detection, live/dead staining, cell proliferative and apoptotic assay, and Western blot were performed. The IPS exhibited sufficient biocompatibility by hemolysis and serum biochemical tests. Also, the results suggested that IPS significantly inhibited HCC cell proliferation and promoted cell apoptosis. More importantly, marked anti-tumor growth effects via inhibiting cell proliferation and promoting tumor cell death were observed in an orthotopic xenograft HCC model. Therefore, our newly proposed nanotheranostic agent for combined chemotherapeutic and photodynamic therapy notably improves the therapeutic effect of sorafenib and has the potential to be a new alternative option for HCC treatment.

O2-Generating Fluorescent Carbon Dot-Decorated MnO2 Nanosheets for “Off/On” MR/Fluorescence Imaging and Enhanced Photodynamic Therapy

“…The photocytotoxicity of HA-MnO 2 −CDs was further evaluated by Live/Dead staining of MDA-MB-231 cells. 63 MDA-MB-231 cells were inoculated on a Φ35 mm Petri dish and incubated at 37 °C for 24 h. Then, HA-MnO 2 −CDs (1 mg/mL) were added to the Petri dish containing cells and incubated at 37 °C for 2 h. MDA-MB-231 cells containing nanoprobes were irradiated with white light (100 mW/ cm 2 , 400−800 nm) for different times and then stained with calcein AM and PI to label living and dead cells. Finally, fluorescence microscopy was used to observe the cell viability and further evaluate the photocytotoxicity of HA-MnO 2 −CDs.…”

Recent Development of Rhenium-Based Materials in the Application of Diagnosis and Tumor Therapy

“…Cancer detection has become more sensitive and accurate. In the treatment of cancer, radiotherapy (RT) [ 25 , 26 ], chemotherapy [ 27 , 28 , 29 , 30 ], photodynamic therapy (PDT) [ 31 , 32 , 33 , 34 , 35 , 36 ], photothermal therapy (PTT) [ 37 , 38 , 39 ], sonodynamic therapy (SDT) [ 40 , 41 , 42 ], immunotherapy [ 43 , 44 , 45 ], starvation therapy (ST) [ 33 , 46 , 47 ], magnetothermal therapy (MHT) [ 48 , 49 ], and other therapies have also shown good anticancer effects. As a remarkable diagnostics reagent candidate, the Re element has attracted the attention of many researchers because of its unique physical and chemical properties.…”

Imidazolium-Based Heavy-Atom-Free Photosensitizer for Nucleus-Targeted Fluorescence Bioimaging and Photodynamic Therapy

“…In the realm of PSs, the incorporation of heavy atoms has traditionally been pursued to enhance intersystem crossing (ISC) processes, thereby promoting ROS generation. − However, concerns surrounding the cost and dark toxicity associated with heavy atoms have driven researchers to explore alternative molecular designs that employ heavy-atom-free PSs. − Recent advancements have focused on strategies such as thionation-enhanced spin–orbit coupling (SOC), ,, reduction of singlet–triplet energy gap (Δ E S–T ), − and enhanced ISC process by charge recombination, , twisted π-systems, or radical. − Despite the significant improvements achieved in triplet formation and 1 O 2 generation, heavy-atom-free PSs often exhibit low or quenched fluorescence emission, limiting their suitability for fluorescence bioimaging applications. This phenomenon can be attributed to a negative correlation between radiative decay and the ISC process, where energy is dissipated through nonradiative decay pathways .…”

“…MIC (μg/mL) of NI-Cz against Various Bacterial Strains: MRSA (1), S. aureus(2), B. subtilis (3), E. faecalis (4), L. monocytogenes(5), ESBL (6), E. coli(7), S. typhimurium (8), K. pneumonia(9), and V. parahaemolyticus(10) a and subsequently washed with 100 mL of hexane, affording the desired product as a white powder.NI-H (yield 75%):1 H NMR (400 MHz, DMSO-d 6 ): δ 9.85 (s, 1H), 8.58 (d, J = 15.9 Hz, 2H), 8.19 (ddd, J = 12.8, 6.4, 3.3 Hz, 2H), 7.66 (ddd, J = 8.9, 6.4, 3.3 Hz, 2H), 4.21−4.09 (m, 6H); ESI HRMS m/z = 197.1076 [M + H] + calcd for C 13 H 12 N 2 O = 196.10. NI-Cz (yield 81%): 1 H NMR (400 MHz, DMSO-d 6 ): δ 8.83 (d, J = 1.6 Hz, 1H), 8.72 (s, 2H), 8.37−8.22 (m, 3H), 8.07 (d, J = 8.J = 8.3, 7.1, 1.2 Hz, 2H), 7.38 (ddd, J = 7.9, 7.1, 0.9 Hz, 2H), 4.13 (s, 6H); 13 C NMR (101 MHz, DMSO-d 6 ): δ 154.26, 141.69, 140.08, 133.55, 131.74, 128.88, 127.74, 127.19, 127.08, 123.80, 121.43, 121.31, 119.80, 111.19, 110.50, 33.69; ESI HRMS m/ z = 438.1968 [M] + calcd for C 31 H 24 N 3 = 438.20.…”