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Intra-iliac Artery Injection for Efficient and Selective Modeling of Microscopic Bone Metastasis
Published on: September 26, 2016
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Beyond Antiresorptive Activity: Risedronate-Based Coordination Complexes To Potentially Treat Osteolytic Metastases.
Gabriel Quiñones Vélez1,2, Lesly Carmona-Sarabia1,2, Alexandra París Santiago1,2
1Department of Chemistry, University of Puerto Rico, Río Piedras, San Juan, Puerto Rico 00931, United States.
ACS Applied Bio Materials
|February 14, 2023
Summary
This study developed novel bisphosphonate-based coordination complexes (BPCCs) using risedronate (RISE) and bioactive metals. The resulting nano-Ca@RISE formulation shows enhanced bone binding and targeted cancer cell toxicity, offering new therapeutic potential.
Area of Science:
- Materials Science: Development of novel bisphosphonate-based coordination complexes (BPCCs).
- Nanotechnology: Synthesis and characterization of nano-formulated bisphosphonate complexes.
- Pharmacology: Investigation of pH-dependent drug release and targeted cytotoxicity.
Background:
- Bisphosphonates, such as risedronate (RISE), are crucial in treating bone diseases.
- Current limitations include systemic side effects and suboptimal drug delivery.
- Developing new formulations can improve efficacy and reduce toxicity.
Purpose of the Study:
- To synthesize and characterize bisphosphonate-based coordination complexes (BPCCs) using risedronate and bioactive metals (Ca2+, Mg2+, Zn2+).
- To evaluate the pH-dependent dissolution profiles and stability of these complexes.
- To assess the bone-binding affinity, particle size stability, and in vitro cytotoxicity of the nano-formulated complex, nano-Ca@RISE.
Main Methods:
- Synthesis of RISE-metal coordination complexes (RISE-Ca, RISE-Mg, RISE-Zn).
- Structural elucidation using single crystal X-ray diffraction.
- pH-dependent dissolution studies in simulated physiological fluids (PBS and FaSSGF).
- Nanoemulsion method (phase inversion temperature) for particle size reduction.
- In vitro binding assays to hydroxyapatite and cytotoxicity assays against cancer and normal cell lines.
Main Results:
- Novel RISE-based BPCCs were successfully synthesized and structurally characterized.
- The complexes exhibited pH-dependent solubility: lower in neutral PBS and higher in acidic FaSSGF, indicating controlled release potential.
- Nano-Ca@RISE demonstrated enhanced binding to hydroxyapatite (1.7x higher than RISE) and significant, specific cytotoxicity against MDA-MB-231 cancer cells at lower concentrations, with no observed toxicity to normal osteoblast cells.
Conclusions:
- Bisphosphonate-based coordination complexes, particularly nano-Ca@RISE, offer a promising platform for enhanced bone targeting and cancer therapy.
- The pH-dependent degradation facilitates controlled release of risedronate in specific microenvironments.
- Nano-Ca@RISE exhibits improved bone affinity and potent, selective anti-cancer activity, expanding therapeutic applications beyond antiresorptive effects.
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