A proposal is herein examined for a novel yet simple design of a polymeric nanogel, with tumor targeting properties and a controllable phototoxicity, utilizing a low molecular weight-hyaluronic acid (HA(LM))/photosensitizer conjugate. HA(LM) was acetylated prior to being dissolved in DMSO (Ac-HA(LM)) and then was conjugated with different amounts of pheophorbide a (Pba), resulting in the formulation of self-organizing nanogels in aqueous solutions (Ac-HA-Pba 1, 2, and 3). The nanogels observed were below 200 nm in size, with a monodispersed size distribution. The nanogels displayed auto photoquenching qualities in PBS, while their fluorescent intensity strongly correlated with the amount of Pba in the organic solvent (DMSO or DMF). The critical self-quenching concentration (CQC) of the conjugates was found to have decreased as the content of Pba rose. Although Pba was conjugated with HA, the nanogel's photoactivity, in terms of fluorescent properties, singlet oxygen generation, and photocytotoxicity, was approximately maintained. Confocal imaging and FACS analysis showed that Ac-HA-Pba nanogels were rapidly internalized into HeLa cells via an HA-induced endocytosis mechanism, a process which could be blocked with the application of an excess of HA polymer. The results of the study indicate that HA-based nanogels can potentially be applied in photodynamic therapy (PDT).
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