PEGylated Chitosan Nanocarriers for Light Activated Cancer Therapy - Synthesis and Characterization Ingolfur Magnusson 1, Elvar Örn Viktorsson 1, Vivek S. Gaware 1, Mar Masson 1* 1 Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland. In recent decades, derivatives of natural carbohydrate polymers like chitosan have received attention for their possible utilization in nanoscale drug delivery systems. Such systems can be used to overcome some of the problems associated with many traditional anti-cancer agents, such as low solubility and ineffective tumor targeting[1]. Drug-polymer conjugates have now become well established nanoscale systems which can overcome barriers in cancer therapy by improving solubility of lipophilic drugs in order to achieve more specific tumor targeting by taking advantage of the enhanced permeability and retention (EPR) effect[2]. In the current study, lipophilic photosensitizer and polar derivatives of triethyleneglycol (TEG) were attached to the backbone of TBDMS- O-protected chitosan. Nucleophilic and electrophilic substitutions were utilized for these reactions. The main objective of this research was to synthesize neutral amphiphilic nanocarriers (drug-polymer conjugates) with suitable properties for photochemical internalization (PCI). Figure 1. Schematic illustration of the main objectives Figure 2. 1 H NMR of TEGylated-TPP-piperazine chitosan nanocarrier Figure 3. Size distibution measurment of chitosan nanoparicles measured by DLS Figure 4. Partition experiment A) TPP-PIP in organic phase B) TEGylated TPP-PIP-chitosan in aqueous phase DLS measurment shows that the chitosan material forms nanoparticles with avarge diameter of 216 nm and Z-potential of 86,82 Mv (Figure 3). The partion experiment indicates that the chitosan polymer is watersoluble and that the TPP-PIP moiety is lipophilic (Figure 4). From the results it´s clear that a novel nanoparticle drug-polymer conjugate has been synthesized with suitable properties for light activated therapy. This new chitosan nanocarrier is hydrophilic and forms stable nanoparticles with average diameter of 216 nm. The chemical properties of the TEG-TPP-PIP-chitosan nanocarrier can be utilized in targeted drug delivery such as PCI. References [1] Duncan, R. (2006). Polymer conjugates as anticancer nanomedicines. [Review]. Nature Reviews Cancer, 6(9), [2] Brannon-Peppas, L., & Blanchette, J. O. (2004). Nanoparticle and targeted systems for cancer therapy. [Review]. Adv Drug Deliv Rev, 56(11), Acknowledgment University of Iceland Research fund and Genis ehf. AimAim IntroductionIntroduction Chitosan used for the synthesis (95% DD, 95 cp) was provided from Genis EHF, Iceland. All other chemicals were commercially available. To analyze the synthesized compounds, 1 H NMR, 13 C NMR spectra were recorded on a Bruker Avance 400 MHz NMR Spectrometer. Mass spectra were recorded on a Bruker micrOTOF-Q instrument with ESI. UV-Vis measurements were recorded on a Perkin-Elmer Lambda 25 UV-Vis. All DLS and zeta potential measurements were performed on a Nanotrac wave-Zeta (ZS), (Microtrac, USA). Materials and Methods ResultsResults ConclusionsConclusions 1 H NMR spetra in Figure 2 shows that the chitosan polymer synthesized, has TEG and tetraphenylporphyrine (TPP) in it´s backbone.