Conjugates between PS and modified albumin can be readily and specifically taken up by macrophages via the high-capacity scavenger receptor. Tumor-associated macrophages (TAMs) can be selectively killed or modified by the appropriate PDT regimen.
It has become apparent in recent years that TAMs are partly responsible for the growth, invasion and metastasis of tumors and are therefore a valid target for cancer therapy. This may be accomplished by a binary approach in which the PS-conjugate targets the macrophages and the spatial confinement of the light delivery ensures that only TAMs (bad) are killed and other macrophages (good) are spared. We are studying the correlation between precise conjugate structure and scavenger receptor subtypes (SRA or CD36). The long-term goal is to be able to specifically target certain macrophage phenotypes and activation state for photodestruction.
Hamblin MR, Miller, JL, Ortel B. Scavenger-receptor targeted photodynamic therapy. Photochem Photobiol 2000;72(4):533-40.
Hamblin MR, O’Donnell DA, Huzaira M, Zahra T. Scavenger receptor-targeted photodynamic therapy of J774 tumors in mice: tumor response and concomitant immunity. Proc SPIE; 2002. Vol 4617: p. 1-10.
Demidova TN, Hamblin MR. Macrophage targeted photodynamic therapy. Int J Immunopathol Pharmacol 2004; 17(2):117-26.
Liu Q, Hamblin MR. Macrophage-targeted photodynamic therapy: scavenger receptor expression and activation state. Int J Immunopathol Pharmacol. 2005, 18: 391-402.
Anatelli F, Mroz P, Liu Q, Yang C, Castano AP, Swietlik E, Hamblin MR. Macrophage-targeted photosensitizer conjugate delivered by intratumoral injection. Mol Pharmaceut. 2006, 6: 654-664.