Abstract

Clinically used small-molecular photosensitizers (PSs) for photodynamic therapy (PDT) share similar disadvantages, such as the lack of selectivity towards cancer cells, short blood circulation time, life-threatening phototoxicity, and low physiological solubility. To overcome such limitations, the present study capitalizes on the synthesis of ultra-small hydrophilic porphyrin-based silica nanoparticles (core–shell porphyrin-silica dots; PSDs) to enhance the treatment outcomes of cancer via PDT. These ultra-small PSDs, with a hydrodynamic diameter less than 7 nm, have an excellent aqueous solubility in water (porphyrin; TPPS3-NH2) and enhanced tumor accumulation therefore exhibiting enhanced fluorescence imaging-guided PDT in breast cancer cells. Besides ultra-small size, such PSDs also displayed an excellent biocompatibility and negligible dark cytotoxicity in vitro. Moreover, PSDs were also found to be stable in other physiological solutions as a function of time. The fluorescence imaging of porphyrin revealed a prolonged residence time of PSDs in tumor regions, reduced accumulation in vital organs, and rapid renal clearance upon intravenous injection. The in vivo study further revealed reduced tumor growth in 4T1 tumor-bearing bulb mice after laser irradiation explaining the excellent photodynamic therapeutic efficacy of ultra-small PSDs. Thus, ultrasmall hydrophilic PSDs combined with excellent imaging-guided therapeutic abilities and renal clearance behavior represent a promising platform for cancer imaging and therapy.