Mesoporous Polydopamine Nanotherapeutics for MRI-Guided Cancer Photothermal and Anti-Inflammatory Therapy

Yang Liu,1,* Chunan Wang,1,* Sitong Liu,1,* Hangzhan - Ma,2 Jiayun Xu,3 Kai Jiang,1 Ruitao Lu,4 Xintao Shuai,5 Jinming Wang,3 Zhong Cao1 1School of Biomedical Engineering, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Oral Implantology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, People’s Republic of China; 4Shenzhen International Institute for Biomedical Research, Shenzhen, Guangdong, People’s Republic of China; 5Nanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhong Cao; Jinming Wang, Email [email protected]; [email protected]: As a burgeoning cancer treatment modality, photothermal therapy (PTT) has shown robust anti-tumor effects. However, it still faces numerous challenges, such as triggering an inflammatory response and potentially increasing the risk of cancer recurrence. To address these concerns, integration of PTT with anti-inflammatory therapies presents a promising approach to enhance the efficacy of cancer treatment and meanwhile reduce the risk of recurrence.Methods: In this study, Gd3+ was first chelated with dopamine to create Gd-DA chelates, and then the mesoporous dopamine nanoparticles MX@Arg-Gd-MPDA (MAGM NPs) were synthesized by combining arginine (Arg) and the anti-inflammatory medication meloxicam (MX). The photothermal properties of MAGM NPs were then defined and examined; the in vivo MRI imaging effect, as well as MAGM NPs’ anti-cancer and anti-inflammatory efficiency, were tested in a mouse model of breast cancer.Results: The incorporation of Arg doping into MAGM NPs was intended to boost its photothermal conversion efficiency and reactive oxygen species (ROS) scavenging ability. Additionally, synergizing with the anti-inflammatory agent meloxicam (MX) within the nanoparticles aimed to enhance the anti-inflammatory effect following photothermal therapy. Furthermore, gadolinium ions (Gd3+) were chelated into the nanostructure to enable precise T1-T2 dual-mode magnetic resonance imaging (MRI) of the intratumor accumulation profile. This imaging capability was leveraged to guide the implementation of photothermal therapy. Animal experiments demonstrated that MAGM NPs exerted a notable anticancer effect in a 4T1 breast cancer mouse model, under the precise guidance of MRI.Keywords: magnetic resonance imaging, photothermal therapy, anti-inflammatory therapy, mesoporous polydopamine, cancer therapy