Colorectal cancer (CRC) is a common and deadly malignancy, ranking second in terms of mortality and third in terms of incidence on a global scale. The survival rates for CRC patients are unsatisfactory primarily because of the absence of highly effective clinical strategies. The efficacy of existing CRC treatments, such as chemotherapy (CT), is constrained by issues such as drug resistance and damage to healthy tissues. Alternative approaches such as photothermal therapy (PTT), while offering advantages over traditional therapies, suffer instead from a low efficiency in killing tumor cells when used alone. In this context, nanostructures can efficiently contribute to a selective and targeted treatment. Here, we combined CT and PTT by developing a nanoplatform based on polydopamine nanoparticles (PDNPs), selected for their biocompatibility, drug-carrying capabilities, and ability to produce heat upon exposure to near-infrared (NIR) irradiation. As a chemotherapy drug, sorafenib has been selected, a multikinase inhibitor already approved for clinical use. By encapsulating sorafenib in polydopamine nanoparticles (Sor-PDNPs), we were able to successfully improve the drug stability in physiological media and the consequent uptake by CRC cells, thereby increasing its therapeutic effects. Upon NIR stimulus, Sor-PDNPs can induce a temperature increment of about 10 °C, encompassing both PTT and triggering a localized and massive drug release. Sor-PDNPs were tested on healthy colon cells, showing minimal adverse outcomes; conversely, they demonstrated excellent efficacy against CRC cells, with a strong capability to hinder cancer cell proliferation and induce apoptosis. Obtained findings pave the way to new synergistic chemo-photothermal approaches, maximizing the therapeutic outcomes against CRC while minimizing side effects on healthy cells.
Keywords: chemotherapy; colorectal cancer; combination therapy; photothermal therapy; polydopamine nanoparticles.