International Journal of Nanomedicine (Jul 2024)
Mesoporous Graphene Oxide Nanocomposite Effective for Combined Chemo/Photo Therapy Against Non-Small Cell Lung Cancer
Abstract
Peigang Zhang,1,2,* Lingling Zheng,1,3,4,* Xiaorui Zhang,1,3 Miao Liu,1,3 Mingli Li,2 Mengting Zhang,1 Jian-Lin Wu,4 Martin MF Choi,5 Wei Bian1– 3 1Department of Medical Chemistry, School of Basic Medical Science, Shanxi Medical University, Taiyuan, Shanxi, 030000, People’s Republic of China; 2Department of Cardiothoracic Surgery, People’s Hospital of Lvliang, Lvliang, Shanxi, 033099, People’s Republic of China; 3Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Taiyuan, Shanxi, 030000, People’s Republic of China; 4State Key Laboratory for Quality Research of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, People’s Republic of China; 5Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Bian, Department of Medical Chemistry, School of Basic Medical Science, Shanxi Medical University, Taiyuan, Shanxi, 030000, People’s Republic of China, Email [email protected]: Lung cancer is the most common cancer worldwide, among which non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers. Chemotherapy, a mainstay modality for NSCLC, has demonstrated restricted effectiveness due to the emergence of chemo-resistance and systemic side effects. Studies have indicated that combining chemotherapy with phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), can enhance efficacy of therapy. In this work, an aminated mesoporous graphene oxide (rPGO)-protoporphyrin IX (PPIX)-hyaluronic acid (HA)@Osimertinib (AZD) nanodrug delivery system (rPPH@AZD) was successfully developed for combined chemotherapy/phototherapy for NSCLC.Methods: A pH/hyaluronidase-responsive nanodrug delivery system (rPPH@AZD) was prepared using mesoporous graphene oxide. Its morphology, elemental composition, surface functional groups, optical properties, in vitro drug release ability, photothermal properties, reactive oxygen species production, cellular uptake and cell viability were evaluated. In addition, the in vivo therapeutic effect, biocompatibility, and imaging capabilities of rPPH@AZD were verified by a tumor-bearing mouse model.Results: Aminated mesoporous graphene oxide (rPGO) plays a role as a drug delivery vehicle owing to its large specific surface area and ease of surface functionalization. rPGO exhibits excellent photothermal conversion properties under laser irradiation, while PPIX acts as a photosensitizer to generate singlet oxygen. AZD acts as a small molecule targeted drug in chemotherapy. In essence, rPPH@AZD shows excellent photothermal and fluorescence imaging effects in tumor-bearing mice. More importantly, in vitro and in vivo results indicate that rPPH@AZD can achieve hyaluronidase/pH dual response as well as combined chemotherapy/PTT/PDT anti-NSCLC treatment.Conclusion: The newly prepared rPPH@AZD can serve as a promising pH/hyaluronidase-responsive nanodrug delivery system that integrates photothermal/fluorescence imaging and chemo/photo combined therapy for efficient therapy against NSCLC. Keywords: NSCLC, mesoporous graphene oxide, combination therapy, hyaluronidase/pH dual-response, nanodrug delivery system
