Lonidamine liposomes to enhance photodynamic and photothermal therapy of hepatocellular carcinoma by inhibiting glycolysis.

Publisher: BioMed Central Country of Publication: England NLM ID: 101152208 Publication Model: Electronic Cited Medium: Internet ISSN: 1477-3155 (Electronic) Linking ISSN: 14773155 NLM ISO Abbreviation: J Nanobiotechnology Subsets: MEDLINE

Original Publication: London : BioMed Central, 2003-

Carcinoma, Hepatocellular*/drug therapy ; Liver Neoplasms*/drug therapy ; Photochemotherapy* ; Neoplasms*/drug therapy ; Nanoparticles*; Humans ; Liposomes/therapeutic use ; Photothermal Therapy ; Reactive Oxygen Species ; Phototherapy ; Photosensitizing Agents/pharmacology ; Photosensitizing Agents/therapeutic use ; Cell Line, Tumor ; Tumor Microenvironment

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has great promise in the treatment of cancer. However, there are many obstacles that can restrict the therapeutic efficacy of phototherapy. The hypoxic tumor microenvironment can restrict the production of reactive oxygen species (ROS) in PDT. As for PTT, the thermotolerance of cancer cells may lead to ineffective PTT. In this study, IR780 and glycolysis inhibitor lonidamine (LND)-encapsulated liposomes are prepared for photodynamic and photothermal therapy of hepatocellular carcinoma. IR780 can be used as a photosensitizer and photothermal agent for simultaneous PDT and PTT after being irradiated with 808 nm laser. LND can reduce the oxygen consumption of cancer cells by inhibiting glycolysis, which will relieve tumor hypoxia and produce more ROS for PDT. On the other hand, energy supply can be blocked by LND-induced glycolysis inhibition, which will inhibit the production of heat shock proteins (HSPs), reduce the thermotolerance of tumor cells, and finally enhance the therapeutic efficacy of PTT. The enhanced PTT is studied by measuring intracellular HSPs, ATP level, and mitochondrial membrane potential. The antitumor effect of IR780 and LND co-loaded liposomes is extensively investigated by in vitro and in vivo experiments. This research provides an innovative strategy to simultaneously enhance the therapeutic efficacy of PDT and PTT by inhibiting glycolysis, which is promising for future creative approaches to cancer phototherapy.
(© 2023. The Author(s).)

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26-2023-00074 Fundamental Research Funds for the Central Universities; 2021C03048 key research and development project of Zhejiang province; LZ20H160002 key project of Natural Science Foundation of Zhejiang Province

Keywords: Glycolysis; Heat shock proteins; Hypoxia; Lonidamine; Phototherapy

0 (Liposomes)
U78804BIDR (lonidamine)
0 (Reactive Oxygen Species)
0 (Photosensitizing Agents)

Date Created: 20231216 Date Completed: 20231218 Latest Revision: 20231218

20231218

PMC10724989

10.1186/s12951-023-02260-z

38102658