Abstract
BackgroundDespite advances of surgery and neoadjuvant chemotherapy during the past few decades, the therapeutic efficacy of current therapeutic protocol for osteosarcoma (OS) is still seriously compromised by multi-drug resistance and severe side effects. Amplification of intracellular oxidative stress is considered as an effective strategy to induce cancer cell death. The purpose of this study was to develop a novel strategy that can amplify the intracellular oxidative stress for synergistic cascade cancer therapy.Methods and resultsA novel nanocomposite, composed of folic acid (FA) modified mesoporous silica–coated gold nanostar (GNS@MSNs-FA) and traditional Chinese medicine lycorine (Ly), was rationally designed and developed. Under near-infrared (NIR) irradiation, the obtained GNS@MSNs-FA/Ly could promote a high level of ROS production via inducing mitochondrial dysfunction and potent endoplasmic reticulum (ER) stress. Moreover, glutathione (GSH) depletion during ER stress could reduce ROS scavenging and further enable efficient amplification of intracellular oxidative stress. Both in vitro and in vivo studies demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation exhibited excellent antitumor efficacy without noticeable toxicity in MNNG/HOS tumor-bearing mice.ConclusionAll these results demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation could dramatically amplify the intra-tumoral oxidative stress, exhibiting excellent antitumor ability without obvious systemic toxicity. Taken together, this promising strategy provides a new avenue for the effective cancer synergetic therapy and future clinical translation.
Highlights
Osteosarcoma (OS) is the most aggressive bone malignancy in children and adolescents, resulting in significant morbidity and mortality [1]
All these results demonstrated that Gold nanostars (GNSs)@mesoporous silica NPs (MSNs)-folic acid (FA)/Ly coupled with NIR irradiation could dramatically amplify the intra-tumoral oxidative stress, exhibiting excellent antitumor ability without obvious systemic toxicity
The obtained GNS@MSNs-FA NPs were observed by Transmission electron microscope (TEM) which demonstrated particles size around 120 nm and a core–shell structure with a well-defined porous structure, providing a high capacity for drug loading (Fig. 1b)
Summary
Osteosarcoma (OS) is the most aggressive bone malignancy in children and adolescents, resulting in significant morbidity and mortality [1]. Despite advances of surgery and neoadjuvant chemotherapy during the past few decades, the overall survival rates of OS have reached a plateau [2]. These treatments still leave much to be improved, such as multi-drug resistance and severe side effects [3]. Despite advances of surgery and neoadjuvant chemotherapy during the past few decades, the therapeutic efficacy of current therapeutic protocol for osteosarcoma (OS) is still seriously compromised by multi-drug resistance and severe side effects. The purpose of this study was to develop a novel strategy that can amplify the intracellular oxidative stress for synergistic cascade cancer therapy
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