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pH and thermo dual stimulus-responsive liposome nanoparticles for targeted delivery of platinum-acridine hybrid agent.

Abstract：

:The complexes of the type [PtCl(L2)(ACRAMTU)](NO3)2 (ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) were synthesized: PT-ACRAMTU (1), L2 = ethane-1,2-diamine (en); PT(dach)-ACRAMTU (2), L2 = (1R,2R)-1,2-diaminocyclohexane (dach); PT(pda-OH)-ACRAMTU (3), L2 = 2-hydroxy-1,3-propanediamine (pda-OH). The complexes containing diverse diamines exhibit different DNA binding capacity and cytotoxicity. Complex 3 shows excellent capability not only on the strongest non-cisplatin-type DNA damage, but also superior anticancer activity in NCI-H460 cells (IC50 = 0.23 ± 0.05 μM). For overcoming water insolubly and side effects, we encapsulated complex 3 into liposomes. PT@NPs were characterized in terms of particle size, morphology, drug loading capacity (DLC), encapsulation efficiency (EE) and stability. In vitro triggered release showed that the release of the platinum drug was steerable and the release rate was fast under low pH (<7.0) and high temperature (>Tm = 41 °C). PT@NPs showed significant inhibitory effect in NCI-H460 cells. Flow cytometry analysis indicates G0/G1 phase arrest of cells treated with complex 3, whereas cells treated with cisplatin progress to G2/M of the cell cycle. The mechanistic differences validate that complex 3 is a potent anticancer agent superior than current clinical platinum-based therapies. PT@NPs have the potential in drug delivery systems (DDS) for non-small cell lung cancer (NSCLC) therapy.

journal_name

Life Sci

journal_title

Life sciences

authors

Zhou Q,You C,Ling Y,Wu H,Sun B

doi

10.1016/j.lfs.2018.11.052

subject

Has Abstract

pub_date

2019-01-15 00:00:00

pages

41-48

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(18)30773-2

journal_volume

217

pub_type

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