Therapeutic Effects of Zoledronic Acid-Loaded Hyaluronic Acid/Polyethylene Glycol/Nano-Hydroxyapatite Nanoparticles on Osteosarcoma

Abstract

Zoledronic acid (ZOL) has been approved as the only bisphosphonate for the prevention and treatment of metastatic bone diseases with acceptable safety and tolerability. However, systemic or direct injection of ZOL often causes severe side effects, which limits its clinical application. Here, an innovative nano-drug delivery system, ZOL-loaded hyaluronic acid/polyethylene glycol/nano-hydroxyapatite nanoparticles (HA-PEG-nHA-ZOL NPs), has been found to effectively inhibit the proliferation of three types of human osteosarcoma cell lines (143b, HOS, and MG63) at 1–10 μmol/L, while with low cell cytotoxicity on normal cells. The NPs significantly enhanced the apoptosis-related protein expression and tumor cell apoptosis rate. The NPs could also inhibit the proliferation of osteosarcoma cells by blocking the S phase of the cell cycle. In the orthotopic osteosarcoma nude mice model, local injection of the HA-PEG-nHA-ZOL NPs stimulated tumor necrosis, apoptosis, and granulocyte infiltration in the blood vessels. Altogether, the ZOL nano-delivery system possesses great potential for local treatment to prevent local tumor recurrence and can be applied in clinical osteosarcoma therapy.

Polymeric Nanoformulation of Zoledronic Acid Rescues Osteoblasts from the Harmful Effect of its Native Form: An In Vitro Investigation of Cytotoxic Potential on Osteoblasts and Osteosarcoma Cells

“…PLGA was chosen because of its excellent biocompatibility, biodegradability, and most importantly, because of its proven role as a sustained delivery vehicle. [ 14 ] Although there have been various approaches to enhance the therapeutic potential of Zol [ 15 ] towards OS, we are aiming for a safe approach by nanoencapsulation of Zol which accounts for studying the effect on normal bone cells. Our study addresses a query of how Zol will behave on bone cells when it is nanoencapsulated rather than conjugated for targeting.…”

Active targeting schemes for nano-drug delivery systems in osteosarcoma therapeutics

“…The HA-modified multidrug delivery system ( CDDP NP DOX&R848 ) induced apoptosis and immunogenic cell death, greatly inhibiting tumor growth and lung metastasis [166]. The targeted delivery of BPs modified by HA effectively inhibited the in situ recurrences of OS along with antitumor effects [167][168][169]. Xu et al [168] constructed an HA-modified polyethylene glycol/nanohydroxyapatite (HA-PEG-nHA) NPs system for ZOL delivery (Fig.…”

“…The targeted delivery of BPs modified by HA effectively inhibited the in situ recurrences of OS along with antitumor effects [167][168][169]. Xu et al [168] constructed an HA-modified polyethylene glycol/nanohydroxyapatite (HA-PEG-nHA) NPs system for ZOL delivery (Fig. 7d).…”

Pterostilbene-Isothiocyanate Inhibits Proliferation of Human MG-63 Osteosarcoma Cells via Abrogating β-Catenin/TCF-4 Interaction─A Mechanistic Insight

“…Osteosarcomas are primarily caused by mesenchymal cells, which typically occur in the distal and upper portions of the bones, resulting in a significant restriction of movement. 1 Lung metastases are responsible for treatment failures and high mortality rates in osteosarcoma. 2 Although chemotherapy, surgery, and occasional radiotherapy have been used to treat osteosarcoma patients since the 1970s, 5-year survival rates have not improved.…”