Synthesis Of Tumor-targeting Copolymer Imaging Agent Containing Sulfapyridine

Malignant tumor is a one of the major causes of death worldwide．Early accuratediagnosis and early effective treatment is always the best principle to rescue patients’survival. Traditional medical imaging technologies provide doctors the intuitivefigures of tumor beyond certain volumes．So, seeking for an effective tumor-targetedsystem is one of the hottest topics in the tumor early diagnosis. After decades’researches, small targeting molecule drugs was used to support diagnosis for all thevarious technologies. However people found that these technologies may not providetimely and accurate information that the clinic needed. Because these technologies arenot specific to diseased tissue，they lack of specific affinity and can not effectivelyreside on the target tissue. They only enhanced images after the short enhancement. Inthis case，early or small tumorigenesis would be missed by the small targetedmolecule drugs means．Therefore，scientific researchers are making every effort tolook for novel approaches that can detect specific molecular abnormalities of earlytumorigenesis timely and sensitively.Driven by such objective, polymeric carriers have emerged as novel medicineplatform that demonstrated great potentials in Targeting drugs delivery and diagnosticimaging applications over the past decade．We will connect the small targeting drugsto the polymeric carrier which were phagocytized by tumor cells were not easilymetabolized and greatly extended the residence time of the targeting drugs in tumors.The toxicity of targeting drugs will be reduced through the polymer carriers and theharm to normal tissue is relatively small. Therefore, the early diagnosis which madeby the macromolecular targeting drugs of cancer becomes reality.In this work, sulfapyridine and HPMA copolymer were selected as the activetargeting ligands and passive targeting carrier respectively, and a combination of bothis expected to provide synergistic dual targeting （passive targeting and active targeting）drug delivery system. Poly（HPMA）-SPD-DTPA-⁹⁹mTc as dual targeting drug deliverysystem was synthesized and characterized. Poly（HPMA）-DTPA-⁹⁹mTc as passivetargeting drug delivery system and DTPA-⁹⁹mTc as a nontargeting drug deliverysystem were also synthesized. In the same conditions, their cellular uptake wasexamined and compared by MTT assay on mouse hepatoma H22cell line, and their biodistribution was tested and compared on mice bearing hepatoma, in order todetermine the contributions of the nontargeting drug delivery system, passivetargeting drug delivery system and dual targeting drug delivery system.Based on the “Enhanced Permeability and Retention （EPR） effect”, the nanosizeddendrimers have shown great promise in the development of anticancer drug deliverysystems. Chain walking polymerization （CWP） followed by atom transfer radicalpolymerization （ATRP）, can efficiently synthesize water-soluble core-shell [core:polyethylene, PE; shell: oligo（ethylene glycol）, OEG] dendritic nanoparticles withtunable sizes and reactive surface functionalities, which could play a very importantrole in tumor targeted drugs. A key part of this approach is the synthesis of highlyactive late transition metal catalysts, which could produce dendritic polyethylene andcontrol the polyethylene particle diameter in the nanometer range.