Novel nanoparticles generated by polymeric amphiphiles with pi-pi conjugated small molecules for anti-tumor drug delivery.
In recent years, the self-assembly polymeric nanoparticles are widely used for anti-tumor drug delivery. Multiple interactions such as hydrogen bonding, host-guest interaction, hydrophobic interaction and electrostatic interaction have been utilized to generate the nanoparticles. Herein, a new polymeric amphiphile with methoxy poly(ethylene glycol) (mPEG) as hydrophilic block and pi-pi conjugated small molecule N-(9-Fluorenylmethoxycarbonyl)-L-phenylalanines (Fmoc-Phe-OH) instead of hydrophobic polymer chain as lipophilic segment was synthesized. Anti-tumor drug doxorubicin (DOX) was trapped in the self-assembly nanoparticles via the dual hydrophobic and pi-pi stacking interactions. The synthesis and morphology of the self-assembly nanoparticles were studied. The interactions between drug and carrier, release profile, cellular uptake and in vitro anti-tumor efficiency of the drug loaded nanoparticles were investigated in details. The results showed that the amphiphiles self-assembled into spindle nanoparticles with the size around 200 nanometers. The pi-pi stacking interaction between DOX and Fmoc-Phe-OH achieved great performance for the efficient drug encapsulation. The DOX could be sustaingly released for 50 hours. The drug loaded nanoparticles were internalized in HepG2 cancer cells efficiently and exhibited good anti-tumor activity in vitro. The nanoparticles generated by mPEG-Phe-Fmoc amphiphiles provided a new strategy to fabricate polymeric nanoparticles for anti-tumor drug delivery.
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
Xin
X
Deng
Xianghui
X
Xu
Yusi
Y
Lai
Bin
B
He
Zhongwei
Z
Gu
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D056945:Hep G2 Cells; D006801:Humans; D008954:Models, Biological; D058726:Nanoconjugates / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D013501:Surface-Active Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004337:Drug Carriers; D058726:Nanoconjugates; D011108:Polymers; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D004317:Doxorubicin; C028210:monomethoxypolyethylene glycol