Novel Targeted Photosensitizer as an Immunomodulator for Highly Efficient Therapy of T-Cell Acute Lymphoblastic Leukemia.

Abstract

Dasatinib is a kinase-targeted drug used in the treatment of leukemia. Regrettably, it remains far from optimal medicine due to insurmountable drug resistance and side effects. Photodynamic therapy (PDT) has proven that it can induce systemic immune responses. However, conventional photosensitizers as immunomodulators produce anticancer immunities, which are inadequate to eliminate residual cancer cells. Herein, a novel compound 4 was synthesized and investigated, which introduces dasatinib and zinc(II) phthalocyanine as the targeting and photodynamic moiety, respectively. Compound 4 exhibits a high affinity to CCRF-CEM cells/tumor tissues, which overexpress lymphocyte-specific protein tyrosine kinase (LCK), and preferential elimination from the body. Meanwhile, compound 4 shows excellent photocytotoxicity and tumor regression. Significantly, compound 4-induced PDT can obviously enhance immune responses, resulting in the production of more immune cells. We believe that the proposed manner is a potential strategy for the treatment of T-cell acute lymphoblastic leukemia.