Multifunctional nanoparticles as nanocarrier for vincristine sulfate delivery to overcome tumor multidrug resistance.
Multifunctional nanoparticles, Fol/R7 NPs, based on pH-sensitive PLGA-PEG-folate and cell penetrating peptide R7-conjugated PLGA-PEG, were constructed for targeting vincristine sulfate (VCR) to tumor and overcoming multidrug resistance (MDR). In this study, the pH-triggered VCR release was 65.6% during 8 h in pH 5.0, but only 35.8% in pH 7.4, demonstrating that a large amount of VCR released rapidly at weak acidic environment. The VCR-Fol/R7 NPs could significantly enhance cellular uptake and cytotoxicity in MCF-7 and MCF-7/Adr cells when compared to the nanoparticles solely modified by folate or R7. With folate receptor-mediated endocytosis and strong intracellular penetration, VCR-Fol/R7 NPs increased drug accumulation in resistant tumor cells by escaping P-glycoprotein mediated drug efflux. In vivo imaging suggested the active targeting attributed to pH sensitivity and folate receptor-mediated effect could improve tumor targeting efficacy. Indeed, VCR-Fol/R7 NPs exhibited the stongest antitumor efficacy in vivo. Therefore, Fol/R7 NPs are an effective nanocarrier for delivering antitumor drug and overcoming multidrug resistance.
School of Pharmacy, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, P. R. China.
Yuan
Y
Wang
Limei
L
Dou
Huijuan
H
He
Yi
Y
Zhang
Qi
Q
Shen
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000737:chemistry; D058972:Folic Acid Transporters / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D023041:Xenograft Model Antitumor Assays
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D058972:Folic Acid Transporters; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D014750:Vincristine; D005492:Folic Acid
multidrug resistance; multifunctional; nanoparticles; pH sensitive; vincristine sulfate