Precision Matters: Minor Concentration Deviations of DMSO May Cause Major Efficacy Shifts

Dimethyl sulfoxide (DMSO) represents the most common solvent for dispersing hydrophobic materials in aqueous solutions for biological usage. Generally, a DMSO content of below 1% is believed to exert no effect on cells, and thus little attention is given to its influence on drug efficacy. During our recent research on a lipid droplet-targeted photosensitizer, PNA-9, we notice the drastic influence of low-concentration DMSO (<1%) on its photodynamic therapy (PDT) performance. In-depth investigations reveal the significant role of low-concentration DMSO on PNA-9 particle size, which further affects cellular uptake via passive diffusion and results in a drastic PDT effect. We further extend our investigation of low-concentration DMSO effect on other common hydrophobic chemotherapy drugs and photosensitizers. The results uncover the differential influences of low-concentration DMSO: camptothecin (CPT) and TPE-IQ possess similar DMSO effects, whilst the therapy effects of paclitaxel (PCT), bortezomib (BTZ), and DTTPB are not obviously influenced. This work aims to bring the effect of low-concentration DMSO to attention and is expected to benefit the development of biomaterials and comprehensive material performance evaluation.