Induction of intensive tumor suppression by antiangiogenic photodynamic therapy using polycation-modified liposomal photosensitizer.

Abstract

BACKGROUND:

The authors previously observed that antiangiogenic scheduling of photodynamic therapy (PDT) was effective in causing tumor regression through hemostasis. It would thus be expected that photosensitizer entrapped in polycation liposomes (PCLs) would be efficiently taken up in tumor-derived angiogenic vascular endothelial cells due to the strong electrostatic adhesion between the polycation and the plasma membrane, thus resulting in enhanced phototherapeutic efficacy.

METHODS:

Tumors and angiogenesis were induced by subcutaneous injection of Meth-A sarcoma cells into 5-week-old male BALB/c mice. PDT treatment was performed by an intravenous (i.v.) injection of benzoporphyrin derivative monoacid ring A (BPD-MA)-entrapped liposomes or the PCLs (0.25 mg/kg in terms of BPD-MA), followed by exposure to a laser light of 689 nm with 150 J/cm(2) of fluence 15 minutes post injection.

RESULTS:

As a result of PDT on angiogenesis-model mice prepared by the dorsal air sac technique, neovascular destruction after laser irradiation was observed when BPD-MA entrapped in PCLs was used. Furthermore, strong suppression of tumor growth was identified by the PCL-mediated PDT treatment along with a prolonged life span for the mice. Destruction of angiogenic vessels and subsequent tumor cell apoptosis were observed after PCL-mediated PDT treatment in an immunofluorescence study. Interestingly, the biodistribution of the injected BPD-MA that was delivered by PCLs indicated invariable photosensitization levels in tumor tissues.

CONCLUSIONS:

The study revealed that antiangiogenic PDT treatment using a low dose of BPD-MA entrapped in PCLs efficiently induced the destruction of angiogenic vessels and subsequent tumor suppression by vessel occlusion.

• Authors: Yoshito Takeuchi, Kohta Kurohane, Kanae Ichikawa, Sei Yonezawa, Mamoru Nango, Naoto Oku
• Journal: Cancer (Cancer) Vol. 97 Issue 8 Pg. 2027-34 (Apr 15 2003) ISSN: 0008-543X [Print] United States
• PMID: 12673734 (Publication Type: Journal Article)
• Copyright: Copyright 2003 American Cancer Society.

Chemical References

• Amines
• Hydrocarbons
• Liposomes
• Luminescent Proteins
• Photosensitizing Agents
• Platelet Endothelial Cell Adhesion Molecule-1
• Polyamines
• Polyelectrolytes
• Porphyrins
• polycations
• benzoporphyrin D
• Green Fluorescent Proteins
• Polyethyleneimine
• hexadecylamine

Topics

• Air Sacs (blood supply)
• Amines
• Animals
• Apoptosis
• Endothelium, Vascular
• Fluorescent Antibody Technique
• Green Fluorescent Proteins
• Hydrocarbons
• In Situ Nick-End Labeling
• Liposomes
• Luminescent Proteins (metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Neovascularization, Pathologic (drug therapy, metabolism, pathology)
• Photochemotherapy
• Photosensitizing Agents (therapeutic use)
• Platelet Endothelial Cell Adhesion Molecule-1 (metabolism)
• Polyamines
• Polyelectrolytes
• Polyethyleneimine (chemistry)
• Porphyrins (therapeutic use)
• Sarcoma, Experimental (blood supply, pathology)
• Skin Neoplasms (blood supply, pathology)