Mr. Ying Sun Profile

Ying Sun

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Proceedings Article | 1 June 1992 Paper

Polymer-bound meso-chlorin e6 for PDT (Invited Paper)

Nancy Krinick, Ying Sun, D. Joyner, R. Reed, John Spikes, Richard Straight, Jindrich Kopecek

Proceedings Volume 1645, (1992) https://doi.org/10.1117/12.60937

KEYWORDS: Polymers, Tumors, Photodynamic therapy, In vivo imaging, Tissues, Oxygen, Quantum efficiency, Tumor growth modeling, In vitro testing, Photosensitizer targeting

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Two types of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer containing meso- chlorin e₆ monoethylene diamine disodium salt (Mce₆) were synthesized. The Mce₆ was bound via pendant enzymatically degradable oligopeptide side chains (G-F-L-G) in one copolymer and was attached through noncleavable side chains (G) in the other. Preliminary experiments have been undertaken to compare their localization/retention behavior and their tumorcidal activity in vivo (A/J mice; C1300 neuroblastoma). Results of localization/retention experiments indicated that the Mce₆ bound to the noncleavable copolymer was retained in the tumor and other tissues for a prolonged time period compared with free Mce₆ or the Mce₆ bound to the cleavable copolymer. Light activation of the Mce₆ from the cleavable copolymer rendered a substantially more potent biological response in vivo than did the permanently bound Mce₆. It is hypothesized and indirectly supported by photophysical data that both of the polymer-photosensitizer complexes are aggregated (or conformationally altered) under physiological conditions due to their hydrophilic/hydrophobic properties. In buffer at pH 7.4, the quantum yield of singlet oxygen generation by free Mce₆ is three-fold higher than by the Mce₆ bound to a noncleavable copolymer; adding detergent (CTAB), increased the quantum yield of singlet oxygen generation to a value consistent with that of the free Mce₆. In vivo, if a sufficient time lag is allowed after drug administration for tumor cell lysosomal enzymes to cleave the Mce₆ from the polymer containing degradable side chains, the Mce₆ would be released in free form and behave with properties akin to the free drug. Due to the difference in cellular uptake mechanisms for free and bound drugs (and the targeting potential of the copolymer), a much higher local concentration in the tumor compared with surrounding tissue can be achieved with the polymer bound drug than the free photosensitizer. Side effects characteristics of current PDT treatment such as light ultrasensitivity in skin may be reduced by improving localization selectivity.

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