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

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.