A molybdenum oxide-based degradable nanosheet for combined chemo-photothermal therapy to improve tumor immunosuppression and suppress distant tumors and lung metastases

Abstract

Molybdenum oxide (MoOx) nanosheets have drawn increasing attention for minimally invasive cancer treatments but still face great challenges, including complex modifications and the lack of efficient accumulation in tumor. In this work, a novel multifunctional degradable FA-BSA-PEG/MoOx nanosheet was fabricated (LA-PEG and FA-BSA dual modified MoOx): the synergistic effect of PEG and BSA endows the nanosheet with excellent stability and compatibility; the FA, a targeting ligand, facilitates the accumulation of nanosheets in the tumor. In addition, DTX, a model drug for breast cancer treatment, was loaded (76.49%, 1.5 times the carrier weight) in the nanosheets for in vitro and in vivo antitumor evaluation. The results revealed that the FA-BSA-PEG/MoOx@DTX nanosheets combined photothermal and chemotherapy could not only inhibit the primary tumor growth but also suppress the distant tumor growth (inhibition rate: 51.7%) and lung metastasis (inhibition rate: 93.6%), which is far more effective compared to the commercial Taxotere®. Exploration of the molecular mechanism showed that in vivo immune response induced an increase in positive immune responders, suppressed negative immune suppressors, and established an inflammatory tumor immune environment, which co-contributes towards effective suppression of tumor and lung metastasis. Our experiments demonstrated that this novel multifunctional nanosheet is a promising platform for combined chemo-photothermal therapy. Graphical Abstract

A synergistic chemodynamic–photodynamic-photothermal therapy platform based on biodegradable Ce-doped MoOxnanoparticles

“…The calculated photothermal conversion efficiency ( η ) reached 67.7% (Fig. 2d and S5†), which is much higher than those of MoO x nanomaterials, such as Fe–MoO x nanowires (48.5%, 808 nm, 0.7 W cm −2 ), 29 MoO x nanosheets (43.41%, 808 nm, 1.5 W cm −2 ), 24 α-MoO 3− x (44.42%, 808 nm, 0.5 W cm −2 ) 57 and MoO 3− x nanobelts (46.9%, 1064 nm, 0.75 W cm −2 ). 58 The stability of photothermal performance was also of great importance for tumor treatment.…”

“…Nonstoichiometric molybdenum oxide (MoO x ) has attracted great attention in biomedical applications due to its stability in a weakly acidic environment in TME (pH ∼ 5.6) and degradability in a weakly alkaline physiological environment (pH ∼ 7.4) 21–24 and low biotoxicity. In addition, nonstoichiometric MoO x exhibits a strong localized surface plasmon resonance (LSPR) effect which can enable high light absorption property in the Near Infrared (NIR) regime.…”

Research Progress of Photothermal Nanomaterials in Multimodal Tumor Therapy

“…Thus, molybdenum oxide nanomaterials can be used in PDT or PTT for tumors ( 111 , 112 ). Qiu et al ( 35 ) combined folic acid and α-lipoic acid-conjugated mPEG-NH 2 (LA-PEG) and modified BSA with molybdenum oxide nanosheets to prepare multi-functional degradable FA-BSA-PEG/MoOx nanosheets ( Figure 2 ). The results of in vivo and in vitro anti-tumor experiments showed that FA-BSA-PEG/MoOx nanosheets significantly increased the temperature of the tumor site, inducing immunogenic cell death, which triggered an immune response in vivo through the combination of PTT and chemotherapy, inhibiting primary tumor growth (inhibition rate: 51.7%) and lung metastasis (inhibition rate: 93.6%).…”

“… The schematic illustration of the multi-strategy for cancer treatment. (A) The preparation route of the FA-BSA-PEG/MoOx@DTX nanosheet and the in vitro antitumor and degradation experimental design; (B) the elucidation of the mechanism of FA-BSA-PEG/MoOx@DTX + NIR combination therapy for meliorating tumor immunosuppression, inhibiting distant tumor and lung metastasis ( 35 ). Reproduced with permission from ( 35 ).…”

Immune-regulating strategy against rheumatoid arthritis by inducing tolerogenic dendritic cells with modified zinc peroxide nanoparticles

“…After their specific uptake by DCs, modified ZnO 2 NPs decomposed in a pH-responsive manner in the lysosomal acidic microenvironment to release Zn 2+ and H 2 O 2 [ 28 ]. H 2 O 2 can be further catalysed by Cat to produce oxygen (O 2 ), which alleviates the intracellular hypoxic state and assists Zn 2+ in promoting the DC transition into tDCs [ 29 – 31 ], thereby attenuating the immune destruction of RA.…”