High affinity zoledronate-based metal complex nanocrystals to potentially treat osteolytic metastases

Vélez, Gabriel Quiñones; Carmona-Sarabia, Lesly; Raíces, Alondra A. Rivera; Hu, Chunhua T.; Peterson, Esther A.; López-Mejías, Vilmalí

doi:10.1039/d1ma01127h

Cited by 7 publications

(50 citation statements)

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“…From the spectra of the first functionalized product, TiO 2 -core: nano- Ca@ZOLE-shell-†, characteristic growing signals can be observed in the 3,200–2,900 cm –1 region (Figure d). Based on previous Raman spectroscopy analyses reported on previous accounts, these bands could correspond to the hydrogen phosphate H–OPO 2 C moieties (3000–2900 cm –1 ) and the stretching vibrations νO–H/H 2 O (3200–3100 cm –1 ) from the ZOLE-based BPCCs. These signals confirmed the initial appearance of a potential coordination complex, which comprises extensive hydrogen bonding due to the lattice water molecules in its crystal structure.…”

Section: Resultsmentioning

confidence: 73%

“…The MDA-MB-231 cell line represents a model of breast-cancer-induced OM as it possess micro-RNAs involved in the development of bone metastasis. , However, the immortalized human fetal hFOB 1.19 cell line is a homogeneous model that allows the study of osteoblast differentiation; in this study, these cells were employed to imitate the normal human bone microenvironment . The half-maximal inhibitory concentration (IC 50 ) values for ZOLE (0–200 μM) against the MDA-MB-231 and hFOB 1.19 cell lines have been previously reported …”

Section: Resultsmentioning

confidence: 99%

“…Here, TiO 2 could provide a positive effect toward the biofunction of osteoblasts (osteoinduction). In addition, the BPCCs could contribute to regulating the overexpressed activity of osteoclasts (bone resorption inhibition) and providing antitumor effects at the metastatic site. ,,, …”

Section: Introductionmentioning

confidence: 99%

“…Among the BPCCs previously reported, nanocrystals of a zoledronate (ZOLE)-based BPCC (ZOLE-Ca form II) named nano -Ca@ZOLE have demonstrated the greatest potential as therapy for the treatment and prevention of OM. , Compared to other BPCCs, these presented higher thermal and structural stability in physiological media, higher binding affinity (∼2.5 x more than ZOLE) to hydroxyapatite in a relevant time frame (24 h), and higher cytotoxicity effects even at the lowest concentrations against a cancerous cell line model (MDA-MB-231) without inducing any negative effect in normal osteoblast-like cells (hFOB 1.19). , Additionally, compared to other BPs such as alendronate and risedronate, reports on immobilization attempts of ZOLE or its derivatives in titanium surfaces have not been reported. , …”

Section: Introductionmentioning

confidence: 99%

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Functionalization of Titanium Dioxide by In Situ Surface Crystallization of Bisphosphonate-Based Coordination Complexes

et al. 2022

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Functionalization of highly pure rutile phase titanium dioxide (TiO2) particles with a selected bisphosphonate-based coordination complex (BPCC), ZOLE-Ca form II, was achieved through in situ surface crystallization. The hydrothermal reaction of the selected BPCC was carried out in the presence of photoactivated rutile phase TiO2 by ultraviolet irradiation. The reaction time was varied to control the crystal growth of the BPCC around the TiO2 core, resulting in a functionalized material with different shell thicknesses: TiO2-core:nano-Ca@ZOLE-shell-† (5 min) and TiO2-core:nano-Ca@ZOLE-shell-‡ (10 min). The crystal phase assessment of the BPCC and the polymorphic phase purity of the metal oxide were determined after immobilization through Raman spectroscopy and powder X-ray diffraction. The results initially suggested that the crystallization of a shell comprising the selected BPCC surrounding a highly pure rutile phase TiO2 core was achieved through controlled in situ surface crystallization. Morphological changes, elemental composition and exact atomic distribution in the functionalized materials were addressed employing scanning electron microscopy coupled with energy-dispersive spectroscopy. These analyses unambiguously confirmed that after 5 min, successful incorporation of a thin BPCC shell on the surface of the metal oxide particles was achieved. Particle size distribution measurements revealed an average particle size of 495 d.nm for the functionalized material after the immobilization process. Quantitative determination of the BPCC shell content in TiO2-core:nano-Ca@ZOLE-shell-† was determined through thermogravimetric analysis, estimating a ratio of ∼1:3 (TiO2:BPCC). The cytotoxicity of TiO2-core:nano-Ca@ZOLE-shell-† against MDA-MB-231 (cancer cell model) and hFOB 1.19 (normal osteoblast-like cell model) cell lines was investigated. The results demonstrated significant cell growth inhibition for TiO2-core:nano-Ca@ZOLE-shell-† against MDA-MB-231, specifically at a concentration of 7.5 μM (% RCL = 46 ± 2%, 72 h). Under the same conditions, the functionalized material did not present cytotoxicity against hFOB 1.19 (% RCL ∼ 100%). These important outcomes provide evidence of the surface crystallization of BPCCs onto rutile phase TiO2 for the development of a novel functionalized material with the potential to treat and prevent osteolytic metastases.

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Section: Resultsmentioning

confidence: 73%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Functionalization of Titanium Dioxide by In Situ Surface Crystallization of Bisphosphonate-Based Coordination Complexes

et al. 2022

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“…Then, the Cu composites were used as NEGS that solved the glucose oxidation problem with their electrical performance in significant findings. Following that, Cu and Zn were successfully composed into MOF that were elaborated by their electrical biosensor performance with higher API-binding affinity [ 49 ]. Thirdly, Cu and Zn were successfully used as redox stimuli and electrical biosensors for electrical triggers.…”

Section: Introductionmentioning

confidence: 99%

CuZn Complex Used in Electrical Biosensors for Drug Delivery Systems

Miskon

Zaidi

2022

Materials

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This paper is to discuss the potential of using CuZn in an electrical biosensor drug carrier for drug delivery systems. CuZn is the main semiconductor ingredient that has great promise as an electrochemical detector to trigger releases of active pharmaceutical ingredients (API). This CuZn biosensor is produced with a green metal of frameworks, which is an anion node in conductive polymers linked by bioactive ligands using metal–polymerisation technology. The studies of Cu, Zn, and their oxides are highlighted by their electrochemical performance as electrical biosensors to electrically trigger API. The three main problems, which are glucose oxidisation, binding affinity, and toxicity, are highlighted, and their solutions are given. Moreover, their biocompatibilities, therapeutic efficacies, and drug delivery efficiencies are discussed with details given. Our three previous investigations of CuZn found results similar to those of other authors’ in terms of multiphases, polymerisation, and structure. This affirms that our research is on the right track, especially that related to green synthesis using plant extract, CuZn as a nanochip electric biosensor, and bioactive ligands to bind API, which are limited to the innermost circle of the non-enzymatic glucose sensor category.

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Design of Extended Bisphosphonate-Based Coordination Polymers as Bone-Targeted Drug Delivery Systems for Breast Cancer-Induced Osteolytic Metastasis and Other Bone Therapies

Carmona-Sarabia,

Quiñones Vélez,

Escalera-Joy

et al. 2023

Inorg. Chem.

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The coordination between benzene 1,4-bis-(bisphosphonic acid) (BBPA), the bisphosphonate (BP) analogue of benzene 1,4-dicarboxylic acid (BDC), and bioactive metals led to the formation of extended bisphosphonate-based coordination polymers (BPCPs). Four distinct crystalline phases were obtained, namely, BBPA-Ca forms I and II, BBPA-Zn, and BBPA-Mg. Among these, BBPA-Ca forms I (7 × 9 Å 2 ) and II (8 × 12 Å 2 ) possess channels large enough to encapsulate 5-fluorouracil (5-FU), a drug prescribed in combination with BPs to treat breast cancer-induced osteolytic metastases (OM). Dissolution curves show a 14% release of BBPA from BBPA-Ca form II in phosphate-buffered saline, while ∼90% was released in fasted-state simulated gastric fluid. These results suggest that this material is relatively stable in neutral environments yet collapses in acidic conditions. Moreover, the phase inversion temperature method decreased the particle size of BBPA-Ca form II, resulting in nano-Ca@BBPA (∼134 d.nm). Binding assays showed a higher affinity of nano-Ca@BBPA (∼97%) to hydroxyapatite than BBPA (∼70%) and significantly higher binding than commercial BPs, zolendronic (3.0×), and risedronic (2.4×) acids after 24 h. Furthermore, both BBPA-Ca form II and nano-Ca@BBPA presented comparable drug loading and release (∼30 wt % 5-FU) relative to BDC-based CCs (UiO-66, MIL-53, and BDC-Zr) where other pharmaceutical compounds (caffeine, ibuprofen, aspirin, and α-cyano-4-hydroxycinnamic acid) have been encapsulated. Cell viability assays established that drug-loaded nano-Ca@BBPA increases the cytotoxicity of a triple-negative human breast cancer cell line (MDA-MB-231) when compared to 5-FU (%RCV = 8 ± 5 vs 75 ± 1% at a 100 μM). At the same concentration, no significant decrease in cell viability was observed for normal human osteoblast-like hFOB 1.19 cells (%RCV = 85 ± 1%). Collectively, these results demonstrate the feasibility of nano-Ca@BBPA as a potential drug delivery system (DDS), with high affinity to bone tissue, to treat bone-related diseases such as OM.

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High affinity zoledronate-based metal complex nanocrystals to potentially treat osteolytic metastases

Abstract: Formation of several materials denominated as bisphosphonate-based coordination complexes (BPCCs), resulted from the reaction between clinically employed bisphosphonate, zoledronate (ZOLE) and bioactive metals (M2+ = Ca2+, Mg2+ and Zn2+) salts....

Cited by 7 publications

References 46 publications

Functionalization of Titanium Dioxide by In Situ Surface Crystallization of Bisphosphonate-Based Coordination Complexes

Functionalization of Titanium Dioxide by In Situ Surface Crystallization of Bisphosphonate-Based Coordination Complexes

CuZn Complex Used in Electrical Biosensors for Drug Delivery Systems

Design of Extended Bisphosphonate-Based Coordination Polymers as Bone-Targeted Drug Delivery Systems for Breast Cancer-Induced Osteolytic Metastasis and Other Bone Therapies

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