In this paper, the alpha-beta cyclodextrin dimer is designed via "click" chemistry to connect the hydrophilic and hydrophobic segments to form self-assembled noncovalently connected micelles (NCCMs) through host-guest interactions. A peptide containing the Arg-Gly-Asp (RGD) sequence was introduced to NCCMs as a target ligand to improve the cell uptake efficacy, while PEGylated technology was employed via benzoic-imine bonds to protect the ligands in normal tissues and body fluid. In addition, two fluorescent dyes were conjugated to different segments to track the formation of the micelles as well as the assemblies. It was found that the targeting property of NCCMs was switched off before reaching the tumor sites and switched on after removing the poly(ethylene glycol) (PEG) segment in the tumor sites, which was called "tumor-triggered targeting". With deshielding of the PEG segment, the drugs loaded in NCCMs could be released rapidly due to the thermoinduced phase transition. The new concept of "tumor-triggered targeting" proposed here has great potential for cancer treatment.

A series of thermosensitive ABA type triblock poly(e-caprolactone)-bpoly(N-isopropylacrylamide)-b-poly(e-caprolactone) (PCL-PNIPAAm-PCL) copolymers with different molecular weights were synthesized by the combination of ring opening polymerization and reversible addition-fragmentation chain transfer (RAFT) polymerization. The critical micelle concentrations (CMCs) of the resulted four triblock copolymers in aqueous solution were determined to be 33. 8, 39.8, 35.5, and 41.7 mg/L, respectively, by fluorescence spectroscopy using pyrene as a fluorescence probe. Optical absorption measurements showed that the lower critical solution temperatures (LCSTs) of the copolymers were 35.8, 36.2, 35.2, and 36.2 8C, respectively, in distilled water, and 33.9, 34.2, 33.3, 34.6 8C, respectively, in PBS (pH ¼ 6.8, I ¼ 0.1). Transmission electron microscopy (TEM) showed that the self-assembled micelles exhibited a well-defined spherical shape with diameter of around 100 nm. The drug-loaded PCL-PNIPAAm-PCL micelles displayed thermosensitive controlled release behaviors. V V C 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: [3048][3049][3050][3051][3052][3053][3054][3055][3056][3057] 2008

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A methoxy‐poly(ethylene glycol)‐block‐poly(acrylamide‐co‐acrylonitrile) (mPEG‐b‐P(AAm‐co‐AN)) amphiphilic copolymer exhibiting upper critical solution temperature (UCST) behavior is synthesized, and micelles from this copolymer are fabricated. It is found that the thermal responses of these micelles are tunable through balancing the hydrophobic/hydrophilic blocks in the copolymer. The size of the doxorubicin (DOX)‐loaded micelles is dependent on the hydrophobic interaction as well as hydrogen bonding between polymer and drug molecules. As a proof of concept, the drug release behavior is studied in vitro, and the cumulative release of DOX increases at temperature above the UCST of blank micelles. 3‐(4,5‐dimethyl‐thiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assays indicate that these polymers are non‐toxic towards human hepatic carcinoma cells (Bel 7402 cells) as well as human embryonic hepatocytes (L02 cells). DOX‐loaded micelles could effectively enter Bel 7402 cells in 2 h, and display much lower half inhibitory concentration compared with free DOX. These micelles may be exploited as a promising drug carrier for cancer therapeutics.