title: The accumulation of dual pH and temperature responsive micelles in tumors.
abstract: An optimized, biodegradable, dual temperature- and pH-responsive micelle system conjugated with functional group Cy5.5 was prepared in order to enhance tumor accumulation. The Dynamic light scattering (DLS) measurements showed that these diblock copolymers form micelle in PBS buffer with a size of around 50 nm by heating of an aqueous polymer solution from below to above the cloud point (CP). Anticancer drug, doxorubicin was incorporated into the inner core of micelle by hot shock protocol. The size and stability of the micelle were controlled by the copolymer composition and is fine tuned to extracellular pH of tumor. The mechanism then caused pH change and at body temperature which induce doxorubicin release from micelles and have strong effects on the viability of HeLa, ZR-75-1, MCF-7 and H661 cancer cells. Our in vivo results revealed a clear distribution of Doxorubicin-loaded mixed micelle (Dox-micelle) and efficiency targeting tumor site with particles increasing size in the tumor interstitial space, and the particles could not diffuse throughout the tumor matrix. In vivo tumor growth inhibition showed that Dox-micelle exhibited excellent antitumor activity and a high rate of anticancer drug in cancer cells by this strategy.
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan, ROC.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Chen
authors.forename: Li-Chi
authors.initials: LC
authors.lastname: Liao
authors.forename: Pei-Lin
authors.initials: PL
authors.lastname: Lu
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Lo
authors.forename: Hsieh-Chih
authors.initials: HC
authors.lastname: Tsai
authors.forename: Chiung-Yin
authors.initials: CY
authors.lastname: Huang
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Wei
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.forename: Ging-Ho
authors.initials: GH
authors.lastname: Hsiue
mesh_terms: D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry*; D013696:Temperature
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D004317:Doxorubicin