Polymeric micelles incorporating (1,2-diaminocyclohexane)platinum (II) suppress the growth of orthotopic scirrhous gastric tumors and their lymph node metastasis

Targeted therapy of spontaneous murine pancreatic tumors by polymeric micelles prolongs survival and prevents peritoneal metastasis

“…This control of the disease did not come at the expense of side effects, and the repeated administration of DACHPt/m, i.e., once a week for 8 wk, suggests that micelles can be used for prolonged chemotherapy cycles. We have previously reported the efficacy of DACHPt/m against various xenografted tumor models (24)(25)(26)(27). These studies demonstrated that the enhanced accumulation of DACHPt/m in the malignancies, through the EPR effect, leads to the suppression of the growth rate of the tumors.…”

“…DACHPt/m are prepared by polymermetal complexation between DACHPt and the carboxylic groups of biocompatible and biodegradable poly(ethylene glycol)-b-poly (glutamic acid) [PEG-b-P(Glu)] copolymers ( Fig. 1) (23)(24)(25)(26)(27), while the active drug is released from the micelles as a result of the ligand substitution with the chloride in the medium. Because DACHPt/m presents sustained drug release and concomitant micelle dissociation with an induction period of ∼8 h in the extracellular environment, the micelles can circulate stably in the bloodstream in a micelle form with minimal drug release and gradually release the drug after accumulating in solid tumors (25).…”

“…Because DACHPt/m presents sustained drug release and concomitant micelle dissociation with an induction period of ∼8 h in the extracellular environment, the micelles can circulate stably in the bloodstream in a micelle form with minimal drug release and gradually release the drug after accumulating in solid tumors (25). Thus, DACHPt/m have shown remarkably higher antitumor activity than the clinically approved DACH-containing platinum drug, that is, oxaliplatin, reducing the growth rate of several xenografted tumor models, such as human cervical cancer (24), human colon cancer (25), human pancreatic cancer (26), and human gastric cancer (27), due to their prolonged blood circulation and enhanced tumor accumulation.…”

Anticancer nanomedicine and tumor vascular permeability; Where is the missing link?

“…[176][177][178][179][180][181][182][183][184][185][186][187][188][189][190][191]. (C) Comparison of the ratio of free to nanoconstruct associated drugs in tumor tissue normalized across studies as % of injected dose per gram of tissue relative to the animal model used [176,177,184,189,[192][193][194][195].…”

Design of a novel theranostic nanomedicine: synthesis and physicochemical properties of a biocompatible polyphosphazene–platinum(II) conjugate

“…Their initial micellar (dach)Pt conjugate was subjected to optimization to obtain the improved clinical candidate compound (NC-4016), 17 which entered a Phase I clinical trial very recently. 18 There are other reports on micellar block copolymers conjugated with the (dach)Pt moiety. 19,20 We have also shown in our previous reports 21,22 that polyphosphazenes conjugated with the active moiety of OX exhibited excellent tumor selectivity by enhanced permeability and retention (EPR) effect.…”