The ATTEMPTS delivery systems for macromolecular drugs.
Aiming at successful targeted drug delivery - a system that possesses both targeting and prodrug features that can be activated once the system reaches the target site upon systemic administration - would be desired to reduce systemic toxicity. Previously we proposed a heparin/protamine-based system for delivery of protease drugs such as tissue-specific plasminogen activator (t-PA). This approach, termed 'antibody targeted, triggered, electrically modified prodrug-type strategy' (ATTEMPTS), would permit antibody-directed administration of inactive t-PA and allow a subsequent triggered release of the active t-PA at the target site. This system can be adapted to target tumor tissues when protein transduction domain (PTD) peptide such as TAT is incorporated in the ATTEMPTS construct. Both in vitro and preliminary in vivo studies using TAT-gelonin (TAT-Gel) and TAT-asparaginase (TAT-ASNase) conjugates have demonstrated that the on/off regulation of the membrane translocation activity of PTD at tumor target, followed by intracellular delivery of cytotoxic macromolecular drug, can be accomplished. Hence, the PTD-mediated delivery system derived from our previous ATTEMPTS approach is a system that incorporates all of the targeting function, prodrug feature, release mechanism and cell entry mechanism and could become a generic system for delivery of macromolecular drugs.
Kwon
Young Min
YM
Tianjin University, Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, Tianjin, 300072, China.
Li
Yongtao
Y
Naik
Sarita
S
Liang
Jun Feng
JF
Huang
Yongzhuo
Y
Park
Yoon Jeong
YJ
Yang
Victor C
VC
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D006801:Humans; D046911:Macromolecular Substances / Q000008:administration & dosage* / Q000627:therapeutic use*; D010960:Plasminogen Activators / Q000008:administration & dosage / Q000627:therapeutic use; D011355:Prodrugs; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use
D000906:Antibodies; D000970:Antineoplastic Agents; D046911:Macromolecular Substances; D011355:Prodrugs; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator