DOI: 10.6084/m9.figshare.26977669
title: Enhanced biosafety, anticancer and antibacterial photodynamic activities using silver-pyropheophorbide-a nanoconjugates

description: <b>Aim:</b> A study of the enhancement of photodynamic activities of pyropheophorbide-a using PG-Ag-PPa nanoconjugates. <b>Materials & methods:</b> The nanoconjugates were formulated from silver nanoparticles and PPa via amide linkage, then characterized, and their photodynamic activities were examined. <b>Results:</b> The nanoconjugates displayed a higher rate of reactive oxygen species generation, commendable cellular uptake by Eca-109 cancer cells, higher photocytotoxicity toward the cancer cells and better bio-safety. They revealed strong antibacterial activity against <i>Escherichia coli</i> following internal reactive oxygen species generation and membrane disintegration. The <i>in vivo</i> anticancer studies confirmed higher cytotoxicity of the nanoconjugates toward cancer cells and better safety than PPa. <b>Conclusion</b>: Therefore, PG-Ag-PPa nanoconjugates could be considered potential nano photosensitizers for photodynamic therapy of tumors and bacterial infection with good bio-safety. <b>Conjugation:</b> PG-Ag-PPa nanoconjugates (PG-Ag-NCs) were successfully formulated by conjugating PPa (COOH group) with PG-Ag NPs (NH/NH2 groups) via amide linkage. <b>Particle size:</b> The nanoconjugates were oval with an average diameter of 61.9 nm. <b>Photochemical stability:</b> Photochemically, the nanoconjugates were relatively chemically stable for 90 min. <b>Solvatochromism:</b> They possessed the ability to absorb and emit in different solvents. <b>pH response:</b> They displayed a pH response in the range of 4–8, which demonstrated their ability to respond in the acidic tumor microenvironment, whose pH is ∼5.8–6.9. <b>ROS generation rate:</b> The nanoconjugates exhibited a higher rate of singlet oxygen generation than the precursor drug (PPa) by 1.2 folds. <b>ROS quantum yield:</b> They also displayed a higher singlet oxygen quantum yield (0.171) than the precursor drug. <b>Targetability:</b> The nanoconjugates exhibited better-targeted selectivity toward Eca-109 cancer cells with negligible uptake by normal cells. <b>Cytotoxicity:</b> Photodynamic therapy (PDT) showed higher cytotoxicity toward cancer cells with minimal/negligible cytotoxicity toward human umbilical vein endothelial cells normal cells of less than 20% at a 10 μg/ml concentration and an energy dose of 12 J/cm<sup>2</sup>. <b>Cellular uptake:</b> Due to the improved selectivity of cellular accumulation in the cancer cells, the challenges of poor accumulation and poor selectivity could be overcome. <b>Antibacterial activity:</b> The NCs demonstrated commendable activity against <i>Escherichia coli</i> under the PDT effect with proven reactive oxygen species inside the bacteria and total membrane destruction using laser light at 8 J/cm<sup>2</sup> and 10 μg/ml with at least 99% colony-forming unit inhibition ratio at 12 J/cm<sup>2</sup>. <b><i>In vivo</i> antitumor activity</b>: The NCs displayed better Eca-109 tumor growth inhibition <i>in vivo</i> than the precursor at the same dosage, with commendable safety toward the animals indicated by the weight gain. These nanoconjugates could reduce the high drug dose used for PDT using PPa PS. It can be suggested that our nanoconjugates may be safe for normal cells. Therefore, PG-Ag-PPa NCs are potential nano photosensitizers for cancer PDT and antibacterial PDT.