Nanomaterial-mediated photothermal cancer treatment: The pivotal role of cellular uptake on photothermal therapeutic efficacy

Nanomaterial-mediated photothermal therapy (PTT) is expected to play a vital role in the treatment of malignant cells. In this study, Au nanorods (NRs) and silica@Au nanoshells (NSs) were synthesized and characterized to demonstrate the PTT efficiency of two nanomaterials for A549 and HeLa cancer cells under different conditions. To determine the impact of particle uptake and photothermal conversion efficiency on PTT efficiency, the threshold loading particle dosages, cellular particle uptake threshold, and threshold average particle dosages of both nanomaterials were monitored for both types of cancer cells. Both receptor-mediated endocytosis and non-specific endocytosis contributed a certain level of nanomaterial particles to the threshold particle dosages. Cellular uptake experiments were conducted at 4 °C to appraise the contribution of receptor-mediated endocytosis, and chlorpromazine-treated cellular uptake experiments were used to evaluate the contribution of non-specific endocytosis. It is hypothesized that PTT efficiency depends on the threshold average particle dosage and the threshold average particle dosage is the sum of receptor-mediated endocytosis and non-specific endocytosis. This concept can serve as a reference for the use of PTT in animal tests and clinical trials. The challenge of effective PTT efficiency in the use of in vivo and clinical tests was also discussed according to our experimental results.