We report the design, synthesis, and examination of a set of novel near-infrared (NIR) indolium-based carbocyanine dyes as potential photosensitizing agents in antibacterial photodynamic therapy (aPDT). The cyanine dyes differed in net charge and quaternary ammonium content at pH 7.0. This was done to increase interactions with the negatively charged cell walls and cell membrane of Gram-negative bacteria, along with the negatively charged sugar phosphate backbone of B-form DNA. The dyes were strategically designed to incorporate a heptamethine chain framework to shift absorption in the NIR wavelength range to promote deep light penetration through biological tissue. We also advantageously modified the polymethine bridge and indolium rings to enhance hydrophobic interactions, dye stability, and reactive oxygen species (ROS) yields. In this dissertation, we will highlight how increasing the net charge, quaternary amine content, and tuning the hydrophobicity of the dyes substantially accelerated their ability to induce direct DNA strand breaks and inhibition of E. coli cell growth by photosensitizing the production of significant levels of the ROS hydroxyl radicals and singlet oxygen. We also utilized a combination of spectral techniques to ascertain DNA binding modes and determine whether the monomeric and/or aggregated forms of the dyes interact with double helical DNA. Our findings will provide further insight into structural design elements that will progress the advancement of next generation of NIR cyanine-based antimicrobial PDT agents that offer better photodynamic efficacy against combating antibiotic resistant bacteria.