Aerosol technique-based carbon-encapsulated hollow mesoporous silica nanoparticles for synergistic chemo-photothermal therapy

Abstract

Near-infrared (NIR)-responsive drug delivery systems have enhanced tumor ablative efficiency through permeation and retention effects. Graphene oxide (GO) has shown great potential both in photothermal therapy and in drug delivery. Thus, in this study, we designed an ambient spark-generated GO, wrapped on topotecan (TPT)-loaded hollow mesoporous silica nanoparticles (HMSN-NH2-TPT-CGO), to function as an efficient platform for pH-dependent sustained release of TPT. HMSN-NH2-TPT-CGO also exhibited a combined chemo-photothermal effect within a single carrier system. This developed system was stable with a uniform particle size (∼190 nm) and was demonstrated to possess a sufficient heat-absorbing capacity to induce tumor cell ablation. We performed the ablation of tumor cells both in vitro and in vivo in combination with photothermal therapy and chemotherapy using the spark-generated functional GO and HMSN. The prepared nanocarriers demonstrated high cellular uptake, apoptosis, and G0/G1 cell cycle arrest. In vivo study using the MDA-MB-231 xenograft model revealed the ultraefficient tumor ablative performance of HMSN-NH2-TPT-CGO compared with that of free TPT, with no toxic effect on vital organs. Altogether, the optimized nanocarriers presented a significant potential to act as a vehicle for cancer treatment. STATEMENT OF SIGNIFICANCE: This is the first study that uses spark-generated graphene oxide nanoflakes to cover the topotecan (TPT)-loaded hollow mesoporous silica nanoparticles (HMSNs) to treat breast cancer. Dense silica was used as a hard template to prepare the HMSNs attributing to a high drug payload. The concentration of Na₂CO₃ was precisely controlled to minimize the silica etching time within 70 min. The use of the nanographene flakes served a dual purpose, first, by acting as a capping agent to prevent the premature release of drug and, second, by serving as a nano heater that significantly ablates the tumor cells. The prepared nanocarriers (NCs) exhibited effective and enhanced in vitro and in vivo apoptosis, as well as significant tumor growth inhibition even after 15 days of treatment time, with no toxic effect to the vital organs. The NCs enhanced in vitro tumor cell killing effects and served as an effective carrier for in vivo tumor regression, thereby highlighting the enormous potential of this system for breast cancer therapy.

Keywords: Graphene oxide; Hollow mesoporous silica nanoparticles; Near-infrared; Photothermal therapy; Topotecan.