Water-Soluble and Degradable Gelatin/Polyaniline Assemblies with a High Photothermal Conversion Efficiency for pH-Switchable Precise Photothermal Therapy

Photothermal therapy (PTT) is regarded as one of the potential techniques to replace surgery in the treatment of tumors. Polyaniline (PANI) shows better biocompatibility than inorganic reagents, which has been widely used in tumor photoacoustic (PA) imaging and PTT. However, the poor water solubility and nonspecific aggregation of PANI nanoparticles severely restricted their biomedical application. In addition, it is difficult to control the photothermal effect just on cancer cells. Herein, we develop tumor pH-responsive PANI-Gel/Cu assemblies, which can achieve targeted and precise ablation of tumors. Due to the high hydrophilicity of gelatin, the PANI-Gel/Cu assemblies show excellent dispersion in physiological solutions and long-term stability. By taking advantage of the self-doping effect between the carboxyl groups in gelatin and the imine part of the PANI skeleton, the photothermal characteristics of PANI-Gel/Cu assemblies can be promoted effectively by the acid tumor microenvironment, and the PA imaging of PANI-Gel/Cu assemblies can also be activated by tumor pH. Consequently, both the PTT enhancement and PA signal amplification can be triggered under a tumor microenvironment, and PANI-Gel/Cu assemblies can be targeted to cancer cells with the RGD sequences in their gelatin skeleton. In vivo imaging-guided PTT to A549 cancer shows precise treatment with little harm to normal cells, and PANI-Gel/Cu assemblies can disassemble into tiny particles (<15 nm) under laser irradiation. This work overcomes the intrinsic limitation of PANI materials, i.e., poor water solubility and nonspecific aggregation, meanwhile providing a pH-active PANI-based platform for precise and effective ablation of cancer.