Dataset Information

Potentiating bisphosphonate-based coordination complexes to treat osteolytic metastases.

ABSTRACT: The hydrothermal reaction between bioactive metal (Ca2+, Zn2+, and Mg2+) salts and a clinically utilized bisphosphonate, alendronate (ALEN), promotes the formation of several materials denominated as bisphosphonate-based coordination complexes (BPCCs). The systematic exploration of the effect of three variables, M2+/ALEN molar ratio, temperature, and pH, on the reaction yielded an unprecedented number of materials of enough crystal quality for structural elucidation. Five crystal structures were unveiled by single crystal X-ray diffraction (ALEN-Ca forms I and II, ALEN-Zn forms I and II, and ALEN-Mg) and their solid-state properties revealed in tandem with other techniques. The dissolution of these BPCCs was tested and contrasted to that of the commercially employed generic form of Fosamax® Alendronate Sodium, using fasted-state simulated gastric fluid and phosphate-buffered saline solution. Quantification of ALEN content was performed by derivatization with Cu2+, which produced a soluble complex suitable for quantification. The results show that these materials present a pH-dependent degradation. Moreover, a phase inversion temperature (PIT) nano-emulsion method was applied to the synthesis of ALEN-Ca form II. Size distribution analysis demonstrated the efficiency of the PIT-nano-emulsion method to decrease the particle size of this BPCC from ?60 ?m to ?438 d nm. The cytotoxicity of ALEN, ALEN-Ca form II (bulk crystals), and nano-Ca@ALEN (nanocrystals) against the MDA-MB-231 cell line was investigated. Nano-Ca@ALEN form II presents higher cytotoxicity effects than ALEN and ALEN-Ca form II (bulk crystals), showing inhibition of cell proliferation at 7.5 ?M. These results provide evidence of the structure, stability, dissolution and cytotoxicity properties of ALEN-based BPCCs and pave the way for better formulation strategies for this drug through the design of nano-sized BPCCs for the treatment of bone-related diseases.

SUBMITTER: Quinones Velez G

PROVIDER: S-EPMC7106950 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Potentiating bisphosphonate-based coordination complexes to treat osteolytic metastases.

Quiñones Vélez Gabriel G Carmona-Sarabia Lesly L Rodríguez-Silva Waldemar A WA Rivera Raíces Alondra A AA Feliciano Cruz Lorraine L Hu Tony T Peterson Esther E López-Mejías Vilmalí V

Journal of materials chemistry. B 20200301 10

The hydrothermal reaction between bioactive metal (Ca2+, Zn2+, and Mg2+) salts and a clinically utilized bisphosphonate, alendronate (ALEN), promotes the formation of several materials denominated as bisphosphonate-based coordination complexes (BPCCs). The systematic exploration of the effect of three variables, M2+/ALEN molar ratio, temperature, and pH, on the reaction yielded an unprecedented number of materials of enough crystal quality for structural elucidation. Five crystal structures were ...[more]

PMID: 32095795

Similar Datasets

Project description:Intramedullary nailing insertion from the proximal-to-distal femur is frequently performed for impending and complete pathological femur fractures due to osteolytic metastases. After nailing through cancer-laden bone, residual chemotherapy- and/or radiation-resistant tumor may progress. Progression of osteolysis risks future nail failure or pathological fractures. This study assesses the incidence of cancer progression following intramedullary nailing in a femur-only cohort and describes a percutaneous rod-retaining salvage technique. A single-institution, retrospective study was conducted to identify adult patients who underwent intramedullary nailing for femoral osteolytic lesions for complete or impending nail failure from 2016 to 2023. Progression was defined as enlargement of the pre-existing lesion and/or appearance of new lesions on radiographs. Surgical outcomes were assessed with a combined pain and functional score. A total of 113 patients (median age 66.8 years (IQR = 16.4); median follow-up 6.0 months (IQR = 14.5)) underwent intramedullary nailing. Sixteen patients (14.2%) exhibited post-nailing cancer progression. Pre- and postoperative radiation and chemotherapy did not decrease the odds of cancer progression. Three patients underwent initial open surgical salvage consisting of proximal femur replacement arthroplasty, and six patients did not receive salvage due to poor surgical candidacy or patient choice. Seven patients (median follow-up 10.7 months (IQR = 12.9)) received percutaneous salvage. In this group, pain and functional scores improved by 4.0 points (p = 0.0078) at two-week postoperative follow-up and 2.0 points (p = 0.0312) at the most recent follow-up (mean follow-up 13.0 ± 9.4 months). All three nonambulatory patients became ambulatory, and six patients were able to ambulate independently without walking aids. No major complications were reported 30 days postoperatively. Progression of femoral osteolytic metastases may occur following intramedullary nailing. Continued monitoring of the entire femur is needed to maintain improved functional status and to prevent catastrophic progression of pre-existing lesions or appearance of new lesions. In patients with more proximal metastases only, the customary practice of bringing a long nail from the proximal femur to distal metaphysis should be reconsidered. Furthermore, there is concern of mechanical transport of cancer cells during guide wire insertion, reaming, and rod insertion through cancer laden bone to cancer free distal bone.

Project description:This article describes the evaluation of the radiopharmaceutical (64)Cu-CB-TE2A-c(RGDyK) ((64)Cu-RGD) as an imaging agent for osteolytic bone metastases and their associated inflammation by targeting of the alpha(v)beta(3) integrin on osteoclasts and the proinflammatory cells involved at the bone metastatic site.The (64)Cu-RGD radiotracer was evaluated in the transgenic mouse expressing Tax (Tax(+)), which spontaneously develops osteolytic tumors throughout the vertebrae and hind limbs, using biodistribution studies and small-animal PET/CT. Histologic analysis was also performed on Tax(+) mouse tails, using hematoxylin and eosin and tartrate-resistant acid phosphatase to confirm the presence of osteolytic bone lesions and the presence of osteoclasts, respectively. Additionally, a proof-of-principle study was conducted with a small group of Tax(+) animals presenting with osteolytic lesions. These animals were treated with the bisphosphonate zoledronic acid and imaged with (64)Cu-RGD to determine whether this radiopharmaceutical was sensitive enough to detect a response to the bisphosphonate therapy.Biodistribution studies using (64)Cu-RGD demonstrated that Tax(+) mice between the ages of 6 and 12 mo had a greater accumulation of activity in their tail vertebrae than did the wild-type (WT) cohort (P = 0.013). Additionally, Tax(+) mice between the ages of 6 and 12 mo had significantly more tracer activity associated with their tail vertebrae than did Tax(+) mice older than 12 mo (P = 0.003), suggesting that earlier bone metastases cause an increased recruitment of alpha(v)beta(3)-expressing cells. Small-animal PET/CT with (64)Cu-RGD was conducted on Tax(+) and WT mice. On the basis of standardized uptake value analysis, Tax(+) mice had approximately 2-fold more tail-associated activity than did WT animals (P = 0.0157). Additionally, decreases in uptake were observed in the tails of Tax(+) mice after treatment with the osteoclast inhibitor zoledronic acid, and histologic analysis of Tax(+) mouse-tail vertebrae revealed the presence of Tax(+) tumor cells, osteoclasts, and proinflammatory cells within the bone microenvironment.Together, these data suggest that (64)Cu-RGD has the potential to effectively image osteolytic bone metastases and monitor the physiologic changes in the bone metastatic microenvironment after osteoclast-inhibiting bisphosphonate therapy.

Dataset Information

Potentiating bisphosphonate-based coordination complexes to treat osteolytic metastases.

Publications

Potentiating bisphosphonate-based coordination complexes to treat osteolytic metastases.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets