The potential of pH-responsive PEG-hyperbranched polyacylhydrazone micelles for cancer therapy.
pH-responsive hyperbranched polymers have attracted much attention due to their unique properties for tumor-targeted drug delivery. In this study, we describe a pH-responsive drug carrier, poly (ethylene glycol) (PEG)-hyperbranched polyacylhydrazone (HPAH), which can form nanoscale micelles to be used as anti cancer drug carriers with pH-controlled drug release. The molecular structure of PEG-HPAH was confirmed by nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared spectroscopy (FTIR). The drug-loaded micelles with a diameter of approximately 190 nm, were prepared using a dialysis method against PBS with a pH of 8.0. The drug-loaded micelles showed the desired pH-dependent drug release properties. The drug release levels were low at neutral and alkaline pH, but increased significantly with a decrease in the pH of the medium. Intracellular uptake results indicated that the PEG-HPAH-drug micelles could efficiently deliver chemotherapeutic drugs into the cells. In addition, it was found that the subcellular localization of the drug-loaded micelles was different from that of free drugs, in which the drug-loaded micelles were mainly in the cytoplasm. The docetaxel (DTX)-loaded PEG-HPAH micelles presented a high cytotoxic activity against tumor cells in vitro. When combined with the administration of glucose, the PEG-HPAH-DTX micelles exhibited a superior anti-tumor efficacy and a lower systemic toxicity in vivo. The biodistribution profile showed increased accumulated drug levels in tumor tissue and plasma in micelles treated group. The results indicate that the nanoscale PEG-HPAH-DTX micelles may serve as a selective tumor-targeting drug delivery system.
Department of Oral & Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
Jingshuang
J
Yu
School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, China.
Hongping
H
Deng
Department of Oral & Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
Furong
F
Xie
Department of Oral & Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
Wantao
W
Chen
Instrumental Analysis Center, Shanghai Jiao Tong University, China. Electronic address: bshzhu@sjtu.edu.cn.
Bangshang
B
Zhu
Department of Oral & Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China. Electronic address: xuqin_2004@hotmail.com.
Qin
Q
Xu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003692:Delayed-Action Preparations; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D006835:Hydrazones / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D043823:Taxoids / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D014018:Tissue Distribution / Q000187:drug effects
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D006835:Hydrazones; D008823:Micelles; D011108:Polymers; D043823:Taxoids; D000077143:Docetaxel; D011092:Polyethylene Glycols; D004317:Doxorubicin
Drug delivery; Hyperbranched polymers; pH-responsive