Macrophage-Targeted Photosensitizer Conjugate Delivered by Intratumoral Injection

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Abstract
A conjugate between maleylated albumin and a photosensitizer (PS) shows cell type specific targeting to macrophages via the scavenger receptor. Administration of this conjugate to a tumor-bearing mouse followed by illumination may allow selective destruction of macrophages within tumors. There is accumulating evidence that tumor-associated macrophages contribute to tumor growth, invasiveness, metastasis, and immune suppression. We tested the intravenous (IV) injection of a conjugate between maleylated albumin and chlorin(e6) to BALB/c mice bearing three tumor types with differing proportions of tumor-associated macrophages. The accumulation of PS within the tumors after IV injection and 24 h incubation time was disappointing, and we therefore investigated intratumoral (IT) injection. This gave 20−50 times greater concentrations of PS within the tumor compared to IV injection as determined by tissue extraction. Furthermore the amounts of PS in each tumor type correlated well with the numbers of macrophages both as determined by extraction from bulk tumor and fluorescence quantification and as determined by tissue dissociation to a single cell suspension and two-color flow cytometry with macrophage-specific antibodies. IT injection of nonconjugated PS gave lower tumor accumulation that did not correlate with macrophage content. IT injection of targeted macromolecular delivery systems is an underexplored area and worthy of further study. Keywords: Tumor-associated macrophages; photosensitizer targeting; scavenger receptors; intratumoral injection; flow cytometry