Breaking the vicious cycle between tumor cell proliferation and bone resorption by chloroquine-loaded and bone-targeted
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Published online 21 August 2020 | https://doi.org/10.1007/s40843-020-1405-8
Breaking the vicious cycle between tumor cell proliferation and bone resorption by chloroquineloaded and bone-targeted polydopamine nanoparticles 1,2
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Yitong Wang , Hui Chen , Kaili Lin , Ting Ying , Quan Huang , Xiaopan Cai , Jianru Xiao , 1* 1,5* Qiang Zhang and Yiyun Cheng ABSTRACT The vicious cycle between tumor cell proliferation and bone resorption remarkably elevates the progression and metastasis of bone tumors. Here, we fabricated polyethylene glycol-conjugated alendronate-functionalized and chloroquine (CQ)-loaded polydopamine nanoparticles (PPA/ CQ) for efficient treatment of bone tumors via breaking the vicious cycle. The nanoparticles were efficiently accumulated to the bone tissues, especially the osteolytic lesions around tumors. CQ released from PPA/CQ inhibited osteoclastogenesis via preventing the degradation of tumor necrosis factor (TNF) receptor-associated receptor 3 to attenuate the osteolysis in bone tumors. On the other hand, CQ blocked the autophagy in cancer cells, resulting in improved photothermal killing of cancer cells. Finally, the in vivo experiment revealed that PPA/CQ-associated treatment efficiently inhibited both tumor growth and osteolysis. This work suggests that autophagy inhibition-associated photothermal therapy could be a promising strategy for treating malignant bone tumors. Keywords: targeted nanoparticles, cancer therapy, multifunctional nanoparticles, drug delivery, bone targeting
INTRODUCTION Malignant bone tumors frequently occur in clinical
practice [1–3]. For instance, More than 60% of patients who suffer with breast and prostate cancers are diagnosed with bone metastases [4]. The incidence of metastatic bone tumors is continuously increasing due to the prolonged survival of cancer patients [5–7]. Unfortunately, malignant bone tumors are hard to cure [8,9], and the bone resorption-induced skeletal-related events aggravate the malignancy of bone tumors [10–13]. Over 50% of patients who suffer from malignant bone tumors finally develop complicated complications including bone pain, bone fractures and hypercalcaemia [14,15], which significantly affect the life quality and mortality [16]. However, the clinical relief of these complications causes enormous waste of medical resource and high cost of therapy [17]. Therefore, developing new strategies to treat malignant bone tumors is an urgent issue [18–21]. The communication between tumor cells and bone microenvironment is responsible for the malignancy of bone tumors [22–26]. The tumor cells in bone microenvironment secrete cytokines to stimulate osteoclastogenesis, and in turn the mature osteoclasts resorb bone matrix to release growth factors, resulting in enhanced tumor growth, which forms a vicious cycle between tumor cell proliferation and bone resorption [27]. Blocking
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Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China Department of Oral & Cra
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