Experience with Photodynamic Therapy Using Indocyanine Green Liposomes for Refractory Cancer

Abstract

We reported the development of an effective cancer treatment using a multidisciplinary treatment, including photodynamic therapy (PDT) with indocyanine green (ICG) liposomes and a combination of Lentinula edodes mycelia (LEM) and hydrogen gas inhalation therapy. ICG liposomes were prepared by adding 5 mg of ICG to 50 mL liposomes. Later, 25 mL of ICG liposomes were diluted with 250 mL of 5% glucose solution and administered intravenously to the patient. We selected the multi-laser delivery system (MLDS), a laser irradiator for performing PDT. Further, the patients received a combination of LEM and hydrogen gas inhalation therapy throughout the treatment. We reported two cases of PDT therapy, one with middle intrathoracic esophagus carcinoma and the other with hypopharyngeal cancer. In the first case, the MLDS laser was directly attached to the endoscope and directed to the cancer area with wavelengths of 810 nm. After the treatment, a biopsy demonstrated no tumor recurrence. In the second case, the patient was treated with endovascular PDT using ICG liposomes and MLDS fiber optics. Later, tumor shrinkage was demonstrated after the first round and disappeared after six months. In conclusion, the present findings suggest that the effect of PDT using ICG liposomes with LEM and hydrogen gas may eradicate cancer without burdening patients by enhancing tumor immunity.

Keywords: Lentinula edodes mycelia; esophagus carcinoma; hydrogen gas; hypopharyngeal cancer; indocyanine green liposomes; multi-laser delivery system; photodynamic therapy.

Figure 1

(A) Indocyanine green (ICG) (left). Five mg of ICG was dissolved in water and mixed with an 8.85-mM liposome solution as ICG liposomes (right). (B) Image of multi-laser delivery system (MLDS). (C) MLDS optical fiber shining a 635-nm laser (left). The device was modified and installed so that the laser could be applied directly to the target region endoscopically (right).

Figure 2

(A) Endoscopic images of middle intrathoracic esophagus carcinoma in the patient before treatment. An irregular elevation was found in the upper intrathoracic esophagus. (B) After radiation therapy, endoscopic images around the tumor lesion (66 Gy/33 times). (C) Endoscopic images after photodynamic therapy using ICG liposomes. The 635-nm and 810-nm lasers were applied to the periphery of the lesion via optical fiber for 20 min. (D) Endoscopic images after 1 year of treatment completion. Endoscopic disappearance was observed, and no recurrence was observed after over 1 year. (E) One year after the completion of treatment, the stratified squamous epithelium of the esophagus was thickened with parakeratosis in pathological section observation. No atypia was found; thus, no malignant finding was found in this biopsy. (F) CT image before photodynamic therapy. (G) CT image after photodynamic therapy.

Figure 3

(A) Image immediately after the start of photodynamic therapy (PDT) using ICG liposomes. Laser irradiation of 635 nm and 810 nm was applied to the neck via optical fiber for 40 min. (B,C) A similar PDT with ICG liposomes was performed three additional times every other month. (D) Four months after the start of treatment, no tumor tissue was observed. (E) CT image before photodynamic therapy. (F) CT image during photodynamic therapy.

Figure 4

Mechanism of PDT using ICG liposomes. ICG; indocyanine green, EPR; enhanced permeability and retention, DAMPs; damage-associated molecular patterns, Treg; regulatory T-lymphocyte, LEM; Lentinura edodes mycelium, APC; antigen-presenting cell, CTL; cytotoxic T-lymphocyte.