title: Delivery of baicalein and paclitaxel using self-assembled nanoparticles: synergistic antitumor effect in vitro and in vivo.
abstract: OBJECTIVE
  Combination anticancer therapy is promising to generate synergistic anticancer effects to maximize the treatment effect and overcome multidrug resistance. The aim of the study reported here was to develop multifunctional, dual-ligand, modified, self-assembled nanoparticles (NPs) for the combination delivery of baicalein (BCL) and paclitaxel (PTX) prodrugs.
  
  
  METHODS
  Prodrug of PTX and prodrug of BCL, containing dual-targeted ligands of folate (FA) and hyaluronic acid (HA), were synthesized. Multifunctional self-assembled NPs for combination delivery of PTX prodrug and BCL prodrug (PTX-BCL) were prepared and the synergistic antitumor effect was evaluated in vitro and in vivo. The in vitro transfection efficiency of the novel modified vectors was evaluated in human lung cancer A549 cells and drug-resistant lung cancer A549/PTX cells. The in vivo antitumor efficiency and systemic toxicity of different formulations were further investigated in mice bearing A549/PTX drug-resistant human lung cancer xenografts.
  
  
  RESULTS
  The size of the PTX-BCL NPs was approximately 90 nm, with a positive zeta potential of +3.3. The PTX-BCL NPs displayed remarkably better antitumor activity over a wide range of drug concentrations, and showed an obvious synergism effect with CI50 values of 0.707 and 0.513, indicating that double-ligand modification and the co-delivery of PTX and BCL prodrugs with self-assembled NPs had remarkable superiority over other formulations.
  
  
  CONCLUSIONS
  The prepared PTX-BCL NP drug-delivery system was proven efficient by its targeting of drug-resistant human lung cancer cells and delivering of BCL and PTX prodrugs. Enhanced synergistic anticancer effects were achieved by PTX-BCL NPs, and multidrug resistance of PTX was overcome by this promising targeted nanomedicine.
authors.affiliation: Department of Chinese Medicine Integrated Traditional Chinese Medicine and Western Medicine, General Hospital of Ji'nan Command, People's Liberation Army, Ji'nan, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Emergency Department, The Fourth People's Hospital of Ji'nan, Medical School, Tai Shan Medical College, People's Liberation Army, Ji'nan, People's Republic of China.
authors.forename: Mei
authors.initials: M
authors.lastname: Xi
authors.affiliation: Department of Chinese Medicine Integrated Traditional Chinese Medicine and Western Medicine, General Hospital of Ji'nan Command, People's Liberation Army, Ji'nan, People's Republic of China.
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Duan
authors.affiliation: Department of Rehabilitation and Physiotherapy, General Hospital of Ji'nan Command, People's Liberation Army, Ji'nan, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hematology, General Hospital of Ji'nan Command, People's Liberation Army, Ji'nan, People's Republic of China.
authors.forename: Fansheng
authors.initials: F
authors.lastname: Kong
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D044950:Flavanones / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage; D014162:Transfection
chemical_list: D044950:Flavanones; D011355:Prodrugs; C006680:baicalein; D006820:Hyaluronic Acid; D005492:Folic Acid; D017239:Paclitaxel
keywords: combination chemotherapy; multidrug resistance; prodrug-based nano-drug delivery system; self-assembled nanoparticles