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

ABSTRACT 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.