Journal Article

Mesoporous Graphene Oxide Nanocomposite Effective for Combined Chemo/Photo Therapy Against Non-Small Cell Lung Cancer

Zhang, Mengting, Wu, Jian-Lin, Choi, Martin, Liu, Miao, Zhang, Peigang, Li, Mingli, Zhang, Xiaorui, Bian, Wei, Zheng, Lingling

2024

Overview

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. 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. 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. 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.

• Publisher: Dove Medical Press Limited,Taylor & Francis Ltd,Dove Press,Dove,Dove Medical Press
• Subject: Animals / Antineoplastic Agents - administration & dosage / Antineoplastic Agents - chemistry / Antineoplastic Agents - pharmacology / Apoptosis / Aqueous solutions / Cancer / Cancer therapies / Carcinoma, Non-Small-Cell Lung - drug therapy / Carcinoma, Non-Small-Cell Lung - pathology / Carcinoma, Non-Small-Cell Lung - therapy / Cell Line, Tumor / Cell Survival - drug effects / Chemotherapy / Combination therapy / Combined Modality Therapy / Drug delivery systems / Drug Delivery Systems - methods / Drug Liberation / Drugs / Fluorescence / Fourier transforms / Graphene / Graphite / Graphite - chemistry / Humans / Hyaluronic acid / Hyaluronic Acid - chemistry / hyaluronidase/pH dual-response / Light therapy / Lung cancer / Lung cancer, Non-small cell / Lung cancer, Small cell / Lung Neoplasms - drug therapy / Lung Neoplasms - pathology / Lung Neoplasms - therapy / mesoporous graphene oxide / Metastasis / Mice / Mice, Inbred BALB C / Mice, Nude / Nanocomposites / Nanocomposites - chemistry / nanodrug delivery system / Nanomaterials / NSCLC / Optical properties / Original Research / Photochemotherapy / Photochemotherapy - methods / Photodynamic therapy / Photosensitizing Agents - administration & dosage / Photosensitizing Agents - chemistry / Photosensitizing Agents - pharmacology / Porosity / Protoporphyrins - chemistry / Protoporphyrins - pharmacokinetics / Reactive Oxygen Species - metabolism / Tumors / Vehicles / Water / Xenograft Model Antitumor Assays