Optimization of tumor-imaging and therapeutic potential of near-infrared multifunctional agents, and targeted polyacrylamide theranostic nanoplatforms
Marko, Aimee Joy
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The goal of this work was to modify the structural parameters of porphyrin-based agents to optimize their imaging and/or therapeutic potential. In order to achieve our goal, certain chlorins and bacteriochlorins were synthesized, their comparative photophysical properties as well as the impact of certain delivery vehicles in tumor-specificity were investigated. Finally, efforts were also made to develop target-specific multifunctional nanoplatforms by introducing tumor-targeting moieties at the surface of the nanoparticles. The promising results of the parent compound 3-[1’-m-iodobenzyloxyethyl]-2-devinyl pyropheophorbide- a as a theranostic agent inspired us to develop of an improved agent with extended ring system. Among the compounds investigated, a reduced porphyrin (chlorin) bearing a cyclohexenone ring system produced excellent PET-imaging capability with reduced fluorescence imaging and PDT capabilities, due to limited singlet oxygen producing ability. Interestingly, compared to methyl 3(1’-benzyloxy)ethylpyropheophorbide-a the corresponding bacteriochlorin containing two reduced pyrrole rings diagonal to each other, retained its PDT and PET imaging abilities. For investigating the utility of NIR bacteriopurpurinimides as theranostic agents, two structural isomers were derived from bacteriochlorophyll-a in which the five member isocyclic ring was extended to a six-member N-substituted imide ring system yielding the desired compounds (one isomer was found to be more effective than other) with good PDT, fluorescence and PET capabilities, but it also produced higher uptake in liver. On postloading the effective isomer in amino functionalized polyacrylamide nanoparticles reduced the liver uptake to some extent. Finally, the nanoparticle project was further extended by developing polyacrylamide nanoparticles bearing folic acid moieties at the periphery, and a series of functionalized nanoparticles was synthesized and characterized for use in future studies. The initial results are quite promising and provide an opportunity to develop improved agents for cancer imaging with and without PDT. This approach is not limited to PDT and can be used for effective delivery of a variety of compounds, including chemotherapeutics with reduced toxicity.