Mitochondria-targeting near-infrared light-triggered thermosensitive liposomes for localized photothermal and photodynamic ablation of tumors combined with chemotherapy

Abstract

Lonidamine, an anticancer drug that acts on mitochondria, has poor water solubility. Mitochondria are the primary source of cellular reactive oxygen species (ROS), which are necessary for photodynamic therapy. Hence, a mitochondria-targeting drug delivery system loaded with Lonidamine and a ROS-produced photosensitizer could improve the bioavailability of Lonidamine and maximize photodynamic therapeutic efficiency. Here we report, for the first time, new IR-780 and Lonidamine encapsulated mitochondria-targeting thermosensitive liposomes (IL-TTSL). DSPE-PEG2000-NH was coupled with triphenylphosphine to form DSPE-PEG-TPP. The liposomes (IL-TTSL) were self-assembled from DPPC, DSPC, DSPE-PEG-TPP, cholesterol, IR-780 and Lonidamine. Coupled linker modified triphenylphosphine (TPP) is cationic and can selectively accumulate several hundred-fold within mitochondria. Once the liposomes are located inside mitochondria, 808 nm laser irradiation could trigger photosensitizer IR-780 to elevate the local temperature, which could be utilized in photothermal therapy and induce the release of Lonidamine from the thermosensitive liposomes. Meanwhile, IR-780 could release ROS for photodynamic therapy in mitochondria and increase photodynamic therapeutic efficiency. Our results showed that the surface modification of the liposomes with triphenylphosphine cations had good mitochondria-targeting ability. The liposomes exhibited good biocompatibility and all components of the empty liposomes were safe to be used in humans. Few reports were related to IR-780 being used in photodynamic therapy and we proved this function of IR-780. Overall, the stealth liposomes provide a promising new strategy to realize mitochondria-targeting thermosensitive chemo-, photodynamic and photothermal combination therapy with a single light source for lung cancer.

Mitochondria targeting IR780-based nanoGUMBOS for enhanced selective toxicity towards cancer cells

“…8 Importantly, cancer cells have a more hyperpolarized mitochondrial membrane potential (DJ m ) in comparison with normal cells, which makes the uptake of cationic drugs into the cancer cells more favorable. 9 As a result, targeting of mitochondria has emerged as an attractive strategy for efficient and selective cancer chemotherapy. 10,11 Recently, a lipophilic near-infrared (NIR) heptamethine dye, IR780, has been shown to have promising anticancer characteristics that acts on mitochondria.…”

Near-infrared photoresponsive drug delivery nanosystems for cancer photo-chemotherapy

“…As a result, this liposome upon NIR laser irradiation mediated a synergistic PTT/PDT/chemotherapy, greatly inhibiting the growth of human cervical HeLa tumors in living nude mice. Similarly, Cui’s group developed a mitochondria-targeting photothermal responsive liposome via self-assembly of triphenylphosphine (TPP)-coupled DSPE-PEG, DPPC, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, a photosensitizer (IR-780) and lonidamine (LON) [ 61 ]. TPP-binding improved the internalization of the liposome into mitochondria of cancer cells.…”

Precise design strategies of nanomedicine for improving cancer therapeutic efficacy using subcellular targeting

“…65 Mitochondria in cancer cells show greater susceptibility than those in normal tissues. Thus, there is the potential to deliver radiosensitizers, 66 photosensitizers, 67 and theranostics 68 to the mitochondria of cancer cells, aiming at ROS production and oxidative stress, which induce mitochondrial permeability transitions and fundamentally affect the energy supply of cancer cells. All of the above have demonstrated that mitochondria targeting is of great significance for improving antitumor therapy.…”