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

Abstract

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.

Recent Advances of Polyaniline-Based Biomaterials for Phototherapeutic Treatments of Tumors and Bacterial Infections

“…Switching from the EB state to the ES state in the presence of oxidative species or an acidic environment leads to a red shift of PANI’s absorption peak from the visible to the NIR region due to charge transmission between benzenoid and quinoid rings through enhanced electron movement, leading to potential PTT applications [ 14 , 29 ]. Therefore, PANI has been exploited in PTT applications owing to its biocompatibility and high photothermal conversion efficiency [ 14 , 29 , 30 , 31 ]. Unlike organic dyes, PANI exhibits excellent photostability upon light irradiation, thus enabling repeated phototherapeutic treatments [ 28 ].…”

“…It was reported that pH response range of PANI can be tuned by self-doping of PANI through introduction of acidic groups into the PANI chains [ 73 ] or by improving the charge transfer rate via incorporation of conductive nanomaterials into PANI matrix [ 74 ]. When relying on this strategy, researchers have made attempts to improve the application of PANI as PTA in cancer treatment [ 31 , 50 , 51 , 52 ]. Hong and coworkers synthesized PANI nanoparticles by incorporating lauric acid (LA) as a stabilizer and localized dopant [ 50 ].…”

“…Nevertheless, the introduction of nonbiodegradable Au may produce long-term toxicity. To minimize these limitations, Tian and coworkers recently developed a tumor pH environment-responsive PANI-based theranostic agent using bovine serum albumin (BSA) and PANI for PAI and PTT of tumors [ 31 ]. In this study, the intermolecular acid–base reactions between the imine moieties of the PANI backbone and the carboxyl groups of BSA led to a self-doping effect and change in the pH responsive range of PANI thereby redshift of absorption peak from visible to NIR region at a relatively high pH (<7.0) ( Figure 4 ).…”

“…In this study, the intermolecular acid–base reactions between the imine moieties of the PANI backbone and the carboxyl groups of BSA led to a self-doping effect and change in the pH responsive range of PANI thereby redshift of absorption peak from visible to NIR region at a relatively high pH (<7.0) ( Figure 4 ). Furthermore, the as-developed BSA-PANI NPs demonstrated strong PAI performance and PTT in tumor environment both in in vitro and in vivo [ 31 ]. The biocompatibility of BSA-PANI NPs was examined in vitro using non-cancer HUVEC cells.…”

“…The biocompatibility of BSA-PANI NPs was examined in vitro using non-cancer HUVEC cells. As shown in Figure 4 C, the BSA-PANI NPs did not exhibit significant toxicity to HUVEC cells in dark even at high concentrations up to 2 mg/mL indicating that PANI-based PTAs are biocompatible [ 31 ]. These results can provide a possible pathway for the development of PANI-based materials that are responsive to pH of tumor.…”