Optimized Combination of Photodynamic Therapy and Chemotherapy Using Gelatin Nanoparticles Containing Tirapazamine and Pheophorbide a

Abstract

In combination therapy, synergetic effects of drugs and their efficient delivery are essential. Herein, we screened 12 anticancer drugs for combination with photodynamic therapy (PDT) using pheophorbide a (Pba). On the basis of combination index (CI) values in cell viability tests, we selected tirapazamine (TPZ) and developed self-assembled gelatin nanoparticles (NPs) containing both Pba and TPZ. The resulting TPZ-Pba-NPs showed a synergetic effect to kill tumor cells because TPZ was activated under the hypoxic conditions that originated from the PDT with Pba and laser irradiation. After they were injected into tumor-bearing mice via the tail vein, TPZ-Pba-NPs showed 3.17-fold higher blood concentration and 4.12-fold higher accumulation in tumor tissue 3 and 24 h postinjection, respectively. Upon laser irradiation to tumor tissue, TPZ-Pba-NPs successfully suppressed tumor growth by efficient drug delivery and synergetic effects in vivo. These overall results suggest that in vitro screening of drugs based on CI values, mechanism studies in hypoxia, and real-time in vivo imaging are promising strategies in developing NPs for optimized combination therapy.

Rhamnolipid-coated W/O/W double emulsion nanoparticles for efficient delivery of doxorubicin/erlotinib and combination chemotherapy

“…We observed dose-dependent death, indicating efficacy of both drugs. The synergy of combinational therapy can be evaluated using the combinational index (CI), where a value less than one indicates that the drugs are synergetic [ 8 ]. When we calculated CI values from the data, all ratios showed a CI value less than one, which indicates strong synergy of the drug combination (Fig.…”

“…Some of them were synergetic and resulted in better clinical outcomes, but there were many cases that were less effective [ 7 ]. This highlights the importance of finding a synergetic combination of drugs [ 8 ]. Among them, doxorubicin (DOX) and erlotinib (ERL) have shown their pronounced synergy in many cases including glioblastoma, hepatocellular carcinoma, non-small cell lung cancer, and triple-negative breast cancer [ 9 – 12 ].…”

Synergic Antitumor Effect of Photodynamic Therapy and Chemotherapy Mediated by Nano Drug Delivery Systems

“…Polyoligo (ethylene glycol) methacrylate-blockpoly(ε-caprolactone)-azobenzene-poly(εcaprolactone)-block-poly oligo (ethylene glycol) [134] Pyropheophorbide paclitaxel Poly [oligo (ethylene glycol) methyl ether methacrylate] [135] Pheophorbide a Tirapazamine Self-assembled gelatin nanoparticles [136] Chlorin-e6 Doxorubicin Poly(phosphorylcholine) [137] Chlorin-e6 Oridonin Side-chain selenium-grafted polymers [138] porphyrin Doxorubicin Tetra-β-cyclodextrin [139] Chlorin-e6 Gemcitabine Polymeric micelles [140] Chlorin-e6 Gemcitabine Multifunctional polymeric prodrug micelles [141] Chlorin-e6 Paclitaxel Liposomes [142] Chlorin-e6 Docetaxel Hyaluronic acid [143] pyropheophorbide-a camptothecin mPEG with thioketal linker [144] Chlorin-e6 Doxorubicin Block copolymers polystyrene-b-poly (acrylic acid) and oil-soluble [145] Chlorin-e6 Perfluorohexanoate-modified cisplatin…”

Iodinated cyanine dye-based nanosystem for synergistic phototherapy and hypoxia-activated bioreductive therapy

“…Photodynamic therapy (PDT), has been applied in the early diagnosis and treatment of various superficial tumors due to the unique advantages including long-range, controllable, selective, and systemic low toxicity (Cheng et al., 2014 ; Li et al., 2017a , b ; Lee et al., 2021 ). In addition, PDT is reported to trigger the local acute inflammatory response of irradiated tissues, resulting in the rapid local infiltration of neutrophils and macrophages as well as the release of systemic inflammatory mediators (Li et al., 2018a,b ; Zhao et al., 2021 ).…”