Depending on increasing extracellular
protein utilization and altering metabolic programs,
cancer cells could proliferate and survive without restricion by ingesting
human serum albumin (HSA) to serve as nutritional
amino acids. Here, we hypothesize that the consumption of
albumin by
cancer cells could be utilized as an efficient approach to targeted
drug delivery.
Lidamycin (LDM), an antitumor
antibiotic with extremely potent cytotoxicity to cultured
cancer cells, consists of an
apoprotein (LDP) and an active enediyne chromophore (AE). In the present study, a novel
albumin-
lidamycin conjugate was prepared by
DNA recombination and molecular reconstitution. Results show that the IC50 values of
albumin-
lidamycin conjugate (HSA-LDP-AE) for a variety of tested
cancer cells were at subnanomolar levels. At tolerated doses, the
albumin-
lidamycin conjugate significantly inhibited the growth of lung
carcinoma PG-BE1 xenografts by 97.8%. The therapeutic efficacy of the
albumin-
lidamycin conjugate was much stronger than that of free
lidamycin. Meanwhile, the images of
albumin-
lidamycin conjugate showed obvious and lasting
tumor localization and fluorescence enrichment and there was no detectable signal in nontumor locations. Taken together,
albumin-
lidamycin conjugate, a new format of
lidamycin, could be a promising antitumor therapeutic agent and
albumin-integration might be a feasible approach to targeted
antitumor drug delivery.