Tumor pH‐Responsive Albumin/Polyaniline Assemblies for Amplified Photoacoustic Imaging and Augmented Photothermal Therapy

Tumor-microenvironment-responsive theranostics have great potential for precision diagnosis and effective treatment of cancer. Polyaniline (PANI) is the first reported pH-responsive organic photothermal agent and is widely used as a theranostic agent. However, tumor pH-responsive PANI-based theranostic agents are not explored, mainly because the conversion from the emeraldine base (EB) to emeraldine salt (ES) state of PANI requires pH < 4, which is lower than tumor acidic microenvironment. Herein, a tumor pH-responsive PANI-based theranostic agent is designed and prepared for amplified photoacoustic imaging guided augmented photothermal therapy (PTT), through intermolecular acid–base reactions between carboxyl groups of bovine serum albumin (BSA) and imine moieties of PANI. The albumin/PANI assemblies (BSA–PANI) can convert from the EB to ES state at pH < 7, accompanied by the absorbance redshift from visible to near-infrared region. Both in vitro and in vivo results demonstrate that tumor acidic microenvironment can trigger both the photoacoustic imaging (PAI) signal amplification and the PTT efficacy enhancement of BSA–PANI assemblies. This work not only highlights that BSA–PANI assemblies overcome the limitation of low-pH protonation, but also provides a facile assembly strategy for a tumor pH-responsive PANI-based nanoplatform for cancer theranostics.