Advances in Bone‐targeted Drug Delivery Systems for Neoadjuvant Chemotherapy for Osteosarcoma

Liu, Chengjun; Liu, Xiaozhou; Zhang, Lei; Chen, Longbang; Shi, Xin; Wu, Sujia; Zhao, Jianning

doi:10.1111/os.12238

Cited by 37 publications

(26 citation statements)

References 46 publications

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“…In the last decades, material science has led to the development of new nanodevices with unprecedented properties to specifically target organ, tissue, and/or cells . In many cases, these delivery systems have demonstrated improved drug pharmacological activity and less toxicity owing to changes in the pharmacokinetic and biodistribution profiles .…”

Section: Figurementioning

confidence: 99%

A Smart Metal–Organic Framework Nanomaterial for Lung Targeting

et al. 2017

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Despite high morbidity and mortality associated with lung diseases,a ddressing drugs towards lung tissue remains ap ending task. Particle lung filtration has been proposed for passive lung targeting and drug delivery.H owever,toxicity issues derived from the long-term presence of the particles must be overcome.Byexploiting some of the ignored properties of nanosized metal-organic frameworks it is possible to achieve impressive antitumoral effects on experimental lung tumors,e ven without the need to engineer the surface of the material. In fact, it was discovered that, based on unique pH-responsiveness and reversible aggregation behaviors,n anoMOF was capable of targeting lung tissue.A tt he neutral pH of the blood, the nanoMOFs form aggregates with the adequate sizetoberetained in lung capillaries.Within24h they then disaggregate and release their drug payload. This phenomenon was compatible with lung tissue physiology.

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Section: Figurementioning

confidence: 99%

A Smart Metal–Organic Framework Nanomaterial for Lung Targeting

et al. 2017

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“…Osteogenic sarcoma, also referred to osteosarcoma (OS), is the most common primary malignant bone tumor. OS affects patients of all ages but shows a substantially higher incidence in children and early adulthood, which is the leading cause of disabling for childhood and adolescence, platinum compounds‐based therapies are the current global standard for neoadjuvant chemotherapy . The platinum‐based anticancer drugs, including cisplatin (CDDP) (Supplementary Figure S1A), carboplatin and oxaliplatin, are currently among the most potent and widely used chemotherapeutic agents in clinical.…”

Section: Introductionmentioning

confidence: 99%

“…OS affects patients of all ages but shows a substantially higher incidence in children and early adulthood, which is the leading cause of disabling for childhood and adolescence, platinum compounds-based therapies are the current global standard for neoadjuvant chemotherapy. 1,2 The platinum-based anticancer drugs, including cisplatin (CDDP) ( Supplementary Figure S1A), carboplatin and oxaliplatin, are currently among the most potent and widely used chemotherapeutic agents in clinical. They are also used for treating a variety of soild cancers, such as breast, ovarian, cervical, testicular, colorectal, bladder, non-small-cell lung, and head and neck cancers.…”

Section: Introductionmentioning

confidence: 99%

Notch pathway inhibition using DAPT, a γ‐secretase inhibitor (GSI), enhances the antitumor effect of cisplatin in resistant osteosarcoma

Dai

Deng

Guo

et al. 2018

Molecular Carcinogenesis

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Overcoming platinum drug resistance represents a major clinical challenge in osteosarcoma (OS) treatment. The high rates and patterns of therapeutic failure seen in patients are consistent with a steady accumulation of drug-resistant cancer stem cells (CSCs). Notch signaling is implicated in regulating CSCs and tumor resistance to platinum. Thus, we attempt to investigate whether inhibiting of Notch pathway could sensitize cisplatin (CDDP) to CDDP-resistant OS cells and the underlying molecular mechanisms. OS cell lines resistant to CDDP were treated with DAPT, CDDP or combination, we present evidences that DAPT enhances the cytotoxic effect of CDDP in resistant OS by inhibiting proliferation, resulting in G0/G1 cell-cycle arrest, inducing apoptosis, and reducing motility. In addition, DAPT targeting depletes OS stem cells (OSCs), thus increasing tumor sensitivity to platinum, which indicating that a dual combination targeting both OSCs and the bulk of tumor cells are needed for tumor eradication. We also found that the combination of CDDP and DAPT exhibit additive suppression on phosphorylated AKT and ERK, contributing to the anti-cancer effects. In animal model, this combination therapy inhibits the growth and metastasis of CDDP resistant tumor xenografts in nude mice to a greater extent than treatment with either reagent alone. Based on these results, we conclude that CDDP plus DAPT was able to sensitize CDDP-resistant human OS cells to CDDP by downregulation of Notch signaling. CDDP and DAPT combination treatment may be effective and promising for advanced OS.

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“…However, there a considerable number of patients with this disease still suffer from tumor recurrence and distant metastasis following complex treatment (12). Distant metastasis is one of the most important reasons for the failure of treatment in the majority of patients with osteosarcoma (13)(14)(15). The main reason for the distant metastasis of osteosarcoma is the abnormal expression of tumor metastasisrelated genes and metastasis suppressor genes (16,17).…”

Section: Introductionmentioning

confidence: 99%

miR-27a-3p promotes the malignant phenotypes of osteosarcoma by targeting ten-eleven translocation 1

Liu

et al. 2018

Int J Oncol

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Osteosarcoma has become one of the most common primary malignant tumors affecting children and adolescents. Although increasing evidence has indicated that microRNAs (miRNAs or miRs) play important roles in the development of osteosarcoma, the expression of miR‑27a‑3p and its effects on osteosarcoma are not yet fully understood. In the present study, our data demonstrated that the expression of miR‑27a‑3p in osteosarcoma cell lines was significantly higher than that in the normal human osteoblastic cell line, hFOB 1.19 cell (P<0.01). In order to explore the role of miR‑27a‑3p in the development and progression of osteosarcoma, the expression of miR‑27a‑3p was inhibited by transfection of the MG-63 cells with miR‑27a‑3p inhibitor. The results revealed that the cell proliferative ability significantly decreased (P<0.01), the number of apoptotic cells significantly increased (P<0.01) and the number of cells passing through the Transwell membrane was significantly reduced in the group transfected with the miR‑27a‑3p inhibitor (P<0.01). At the same time, the expression of E-cadherin and α-catenin was significantly upregulated (P<0.01), while the expression of vimentin was significantly downregulated in the group transfected with the miR‑27a‑3p inhibitor (P<0.01). Our results also revealed that the mRNA expression of ten-eleven translocation 1 (TET1) in the osteosarcoma cells was significantly downregulated compared with that in the hFOB 1.19 cells (P<0.01). Luciferase reporter system analysis indicated that miR‑27a‑3p recognized the TET1 3'-UTR. The protein expression of TET1 significantly increased in the group transfected with the miR‑27a‑3p inhibitor. The results from CCK-8 assay, flow cytometric assay and Transwell invasion analysis revealed that TET1 knockdown inhibited the biological effects induced by the downregulation of miR‑27a‑3p. Taken together, the findings of this study indicate that miR‑27a‑3p is upregulated, while TET1 is downregulated in human osteosarcoma cells. miR‑27a‑3p inhibition suppresses the proliferation and invasion of osteosarcoma cells, and promotes cell apoptosis via the negative regulation of TET1. miR‑27a‑3p/TET1 may thus be a potential target for the treatment of osteosarcoma.

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Advances in Bone‐targeted Drug Delivery Systems for Neoadjuvant Chemotherapy for Osteosarcoma

Cited by 37 publications

References 46 publications

A Smart Metal–Organic Framework Nanomaterial for Lung Targeting

A Smart Metal–Organic Framework Nanomaterial for Lung Targeting

Notch pathway inhibition using DAPT, a γ‐secretase inhibitor (GSI), enhances the antitumor effect of cisplatin in resistant osteosarcoma

miR-27a-3p promotes the malignant phenotypes of osteosarcoma by targeting ten-eleven translocation 1

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