title: A novel micelle of coumarin derivative monoend-functionalized PEG for anti-tumor drug delivery: in vitro and in vivo study.
abstract: In this paper, a novel micelle for anti-tumor drug delivery was reported. Two 7-carboxymethoxy coumarin molecules were immobilized on the terminal group of a methoxy poly(ethylene glycol) chain via l-lysine as linker. The amphiphilic 7-carboxymethoxy coumarin monoend-functionalized methoxy poly(ethylene glycol) (mPEG-Lys-DCOU) chains were self-assembled micelles. Anti-tumor drug doxorubicin was loaded in the mPEG-Lys-DCOU micelles and the release profile was studied. The cytotoxicity of mPEG-Lys-DCOU was evaluated by NIH 3T3 fibroblasts. The drug-loaded micelles were incubated with HepG2 tumor cells to investigate the in vitro anti-tumor effect. The in vivo inhibition efficacy of drug-loaded micelles was carried out on 4T1 breast cancer animal model. The results showed that both hydrophobic and π-π stacking interactions within mPEG-Lys-DCOU amphiphiles were contributed to the self-assembly. Both blank and drug loaded micelles were monodisperse nanoparticles with the average diameters around 300 nm. The release profile exhibited certain pH dependence. The drug release rate at pH = 5.5 was much faster than that at pH = 7.4. mPEG-Lys-DCOU amphiphiles were non-toxic to NIH 3T3 fibroblasts. Both in vitro and in vivo studies demonstrated that the inhibition efficacy of drug-loaded micelles were comparable to that of doxorubicin hydrochloride. mPEG-Lys-DCOU micelles are promising carriers for anti-tumor drug delivery.
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China.
authors: Yusi
authors: Y
authors: Lai
authors: Youyu
authors: Y
authors: Long
authors: Ying
authors: Y
authors: Lei
authors: Xin
authors: X
authors: Deng
authors: Bin
authors: B
authors: He
authors: Mingming
authors: M
authors: Sheng
authors: Ming
authors: M
authors: Li
authors: Zhongwei
authors: Z
authors: Gu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003374:Coumarins / Q000009:adverse effects / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004339:Drug Compounding; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry*; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D004337:Drug Carriers; D008823:Micelles; D011092:Polyethylene Glycols; D004317:Doxorubicin