The Recombinant and Reconstituted Novel Albumin–Lidamycin Conjugate Shows Lasting Tumor Imaging and Intensively Enhanced Therapeutic Efficacy

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 co...

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Bibliographic Details
Published in:Bioconjugate chemistry 2018-09, Vol.29 (9), p.3104-3112
Main Authors: Li, Liang, Hu, Lei, Zhao, Chun-yan, Zhang, Sheng-hua, Wang, Rong, Li, Yi, Shao, Rong-guang, Zhen, Yong-su
Format: Article
Language:English
Subjects:
Albumin
Amino acids
Antibiotics
Anticancer properties
Cancer
Cell growth
Chemical compounds
Chromophores
Conjugates
Cytotoxicity
Deoxyribonucleic acid
DNA
Drug delivery
Drug delivery systems
Drug therapy
Extracellular matrix
Fluorescence
Human serum albumin
Localization
Lung carcinoma
Medical imaging
Pharmacology
Proteins
Recombination
Serum albumin
Toxicity
Tumors
Xenografts
Xenotransplantation
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Summary: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.
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.8b00456