Bone-Targeted Dual Functional Lipid-coated Drug Delivery System for Osteosarcoma Therapy.

PURPOSE OR OBJECTIVE: Osteosarcoma is well-known for its high incidence in children and adolescents and long-term bone pain, which seriously reduces the life quality of patients. Cisplatin (CDDP), as the first-line anti-osteosarcoma drug, has been used in many anticancer treatments. At the same time, the serious side effects of platinum (Pt) drugs have also attracted widespread attention. To accurately deliver Pt drugs to the lesion site and realize controlled release of Pt drugs, certain modified delivery systems have been extensively studied. METHODS: Among them, liposomes have been approved for clinical cancer treatment due to their highly biocompatibility and superior modifiability. Here, we developed a bone-targeted dual functional lipid-coated drug delivery system, lipid-coated CDDP alendronate nanoparticles (LCA NPs) to target the bone and precisely deliver the drugs to the tumor site. Cell toxicity, apoptosis and cellular uptake were detected to evaluate the anticancer effect for LCA NPs. Furthermore, transwell assay and wound healing assay were conducted to estimate the osteosarcoma cell migration and invasion. Hemolysis assay was utilized to assess the biocapitibility of the kind of NPs. RESULTS: With the aim of bone-targeted unit alendronate (ALD), LCA NPs serve as a rich bone homing Pt delivery system to exert efficient anticancer effects and synergistically reduce bone resorption and bone loss potentially. CONCLUSIONS: By providing a highly biocompatible platform for osteosarcoma therapy, LCA NPs may help to significantly enhance the anticancer effect of Pt and greatly reduce the systemic toxicity and side effects of Pt towards osteosarcoma.

Emerging drugs for the treatment of bone metastasis.

INTRODUCTION: Bone metastases are virtually incurable resulting in significant disease morbidity, reduced quality of life and mortality. Bone provides a unique microenvironment whose local interactions with tumor cells offer novel targets for therapeutic interventions. Increased understanding of the pathogenesis of bone disease has led to the discovery and clinical utility of bone-targeted agents other than bisphosphonates and denosumab, currently, the standard of care in this setting. AREAS COVERED: In this review, we present the recent advances in molecular targeted therapies focusing on therapies that inhibit bone resorption and/or stimulate bone formation and novel anti-tumoral agents that exerts significant effects on skeletal metastases, nowadays available in clinical practice or in phase of development. EXPERT OPINION: New emergent bone target therapies radium-223, mTOR inhibitors, anti-androgens have demonstrated the ability to increase overall survival in bone metastatic patients, other compounds, such as ET-1 and SRC inhibitors, up to now failed to clearly confirm in clinical trials their promising preclinical data.

Bone-Targeted Nanoplatform Combining Zoledronate and Photothermal Therapy To Treat Breast Cancer Bone Metastasis.

Bone metastasis, a clinical complication of patients with advanced breast cancer, seriously reduces the quality of life. To avoid destruction of the bone matrix, current treatments focus on inhibiting the cancer cell growth and the osteoclast activity through combination therapy. Therefore, it could be beneficial to develop a bone-targeted drug delivery system to treat bone metastasis. Here, a bone-targeted nanoplatform was developed using gold nanorods enclosed inside mesoporous silica nanoparticles (Au@MSNs) which were then conjugated with zoledronic acid (ZOL). The nanoparticles (Au@MSNs-ZOL) not only showed bone-targeting ability in vivo but also inhibited the formation of osteoclast-like cells and promoted osteoblast differentiation in vitro. The combination of Au@MSNs-ZOL and photothermal therapy (PTT), triggered by near-infrared irradiation, inhibited tumor growth both in vitro and in vivo and relieved pain and bone resorption in vivo by inducing apoptosis in cancer cells and improving the bone microenvironment. This single nanoplatform combines ZOL and PTT to provide an exciting strategy for treating breast cancer bone metastasis.

Treating patients with renal cell carcinoma and bone metastases.

INTRODUCTION: Bone metastases (BMs) are common and cause morbidity in cancer patients. This review focuses on evidence in BMs from metastatic renal cell carcinoma (mRCC) management and discusses current evidence on the role of systemic treatments in BMs management, bone-targeting agents' benefits in skeletal-related events prevention and local therapeutic approaches to BM in mRCC. Areas covered: A comprehensive review of literature concerning incidence, prognosis, and therapeutic approaches of BMs was performed, focusing on the latest emerging evidence in management of BMs from mRCC. Expert commentary: One-third of mRCC patients present metastatic disease to the bone. BMs impact negatively the prognosis and decrease quality of life. Adequate management of BMs from RCC requires a multimodal evaluation to optimize care and quality of life. Both tyrosine-kinase inhibitors and immunotherapy may be effective in BMs treatment. BMs cause severe complications such as fracture, spinal cord compression, and pain requiring surgery or radiotherapy and several local approaches are available to achieve a local control of the disease. Defining prognosis of systemic disease and identifying the main goal of treatment is crucial for the selection of the best strategy.