New anti-tumor strategy based on acid-triggered self-destructive and near-infrared laser light responses of nano-biocatalysts integrating starvation–chemo–photothermal therapies

Abstract

Background: Inherent limitations of single cancer therapy are overcome by multi-therapy modality, which integrates characteristics of each therapeutic modality and material chemistry. The multi-modal method has the potential for becoming one of the next generation options for cancer treatments. Photothermal therapy (PTT) is an efficient, non-invasive treatment method that can be used on various cancer types. We propose an acid-triggered self-destructing nano-biocatalyst integrated starvation/chemical/photothermal triple therapy that is based on design principles and biomedical applications of GOx cancer treatment methods. Methods: Scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potentials were used to analyze the physical as well as chemical properties of MoS2@DOX/GOx@MnO2 (M@D/G@M). Further, Fourier transform infra-red (FTIR), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) were used to assess the compositions of the nanocatalysts. The biological effects of M@D/G@M on cells were studied in vitro by inverted fluorescence microscopy, confocal laser scanning microscopy (CLSM), flow cytometry, CCK-8 test, and hemolysis test. Treatment effects of the nanocatalysts were evaluated in MHCC-97H tumor BALB/c mice, whose body weights, tumor local temperature, tumor volumes, and tumor histological changes were evaluated. Results: There was a high DOX encapsulation efficiency of M@D/G@M (90.233%). The photothermal conversion efficiency (η) of M@D/G@M is 25.2%, and its oxygen production within 5 min reached 27.5 mg L−1. Cell internalization analysis showed that within 4 h, M@D/G@M was almost completely absorbed by HepG2 cells. Further, the highest red fluorescence and apoptosis effects of dead cells (59.07% apoptosis) as well as the lowest tumor volume index of mice (0.2862%) were observed in the M@D/G@M + pH6.0 + NIR treatment group. Conclusions: Our findings inform the development and applications of multi-modal methods in tumor therapy.