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

Na Qiu,Lei Ye,Yu Zhang,Jicheng Zhang,Dongzhu Liu,Yanan Zhang,Xinru Kong,Xiaoye Yang,Yanwei Xi,Guangxi Zhai,Jianbo Ji

doi:10.1186/s12951-021-01162-2

Na Qiu, Lei Ye + Show 9 more

Open Access

https://doi.org/10.1186/s12951-021-01162-2

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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

Highlights

Even today, cancer remains a significant global health challenge [1]
The design strategy, fabrication and characterization of multifunctional nanosheet The ultrathin blue molybdenum oxide nanosheets were synthesized by a hydrothermal method (Scheme 1A)
A dual-modified Molybdenum oxide (MoOx) (FA-BSA-PEG/MoOx) nanosheet with excellent stability and targeting capability was conducted for breast cancer combined with Photothermal therapy (PTT) and chemotherapy (Scheme 1B)

Summary

Introduction

Cancer remains a significant global health challenge [1]. Despite significant efforts in cancer treatment research over generations, strategies for clinical application remain limited due to the complexity and heterogeneity of tumors and the remarkable difference between in vitro and in vivo conditions [2, 3]. The most promising strategy that overcomes all the above limitations is to fabricate a multifunctional nanocarrier combining multitherapy for the synergistic enhancement of cancer therapy. PTT has the potential to induce immunogenic cell death (ICD), release tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs), and activate the immune response, suggesting a promising approach for the combined chemo-photothermal therapy strategy [9, 10]

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Results

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