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High-Affinity Extended Bisphosphonate-Based Coordination Polymers as Promising Candidates for Bone-Targeted Drug

Lesly Carmona-Sarabia1,2, Gabriel Quiñones Vélez1,2, Darilys Mojica-Vázquez1,2

  • 1Department of Chemistry, University of Puerto Rico, Río Piedras Campus, San Juan, Puerto Rico 00931, United States.

ACS Applied Materials & Interfaces
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PubMed
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New bisphosphonate-based coordination polymers (BPCPs) show promise for treating bone metastases. These materials effectively deliver cancer drugs to bone tissue, exhibiting enhanced cytotoxicity against breast cancer cells without harming healthy bone cells.

Keywords:
bone affinitycoordination polymersextended bisphosphonatespH-dependent degradationtargeted drug delivery

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Area of Science:

  • Materials Science
  • Nanotechnology
  • Drug Delivery

Background:

  • Osteolytic metastases (OM) are a significant complication of breast cancer, often requiring targeted therapies.
  • Bisphosphonates (BPs) are commonly used to treat bone-related diseases, but their drug delivery capabilities can be enhanced.
  • Coordination polymers offer a versatile platform for developing novel drug delivery systems.

Purpose of the Study:

  • To synthesize and characterize extended bisphosphonate-based coordination polymers (BPCPs) using 1,1'-biphenyl-4,4'-bisphosphonic acid (BPBPA) and bioactive metals.
  • To evaluate the drug-loading and release capabilities of BPCPs, specifically for letrozole (LET), an antineoplastic drug.
  • To assess the efficacy of nano-encapsulated BPCPs as a targeted drug delivery system for breast cancer-induced OM.

Main Methods:

  • Synthesis of BPCPs (BPBPA-Ca, BP-BPA-Zn, BPBPA-Mg) through reaction with Ca2+, Zn2+, and Mg2+.
  • Characterization of BPCPs' structure, including channel dimensions and pH-dependent degradation in simulated physiological fluids (PBS and FaSSGF).
  • Preparation of nano-encapsulated Ca@BPBPA (nano-Ca@BPBPA) using the phase inversion temperature nanoemulsion method and assessment of its hydroxyapatite binding affinity.
  • In vitro evaluation of LET encapsulation and release kinetics, and cytotoxicity assays using breast cancer cell lines (MCF-7, MDA-MB-231) and normal osteoblast cells (hFOB 1.19).

Main Results:

  • BPCPs with defined channel sizes were successfully synthesized, capable of encapsulating letrozole (LET).
  • BPCPs exhibited pH-dependent degradation, with BPBPA-Ca showing stability in PBS and structural collapse in FaSSGF.
  • Nano-Ca@BPBPA demonstrated significantly higher binding affinity to hydroxyapatite compared to commercial BPs.
  • Drug-loaded nano-Ca@BPBPA showed enhanced cytotoxicity against breast cancer cells compared to LET alone, with no significant toxicity to normal osteoblasts.

Conclusions:

  • Nano-encapsulated BPCPs are promising drug delivery systems for treating osteolytic metastases and other bone diseases.
  • These materials facilitate bone-targeted drug delivery due to their enhanced affinity and stability in acidic environments.
  • The developed nano-Ca@BPCPs effectively deliver cytotoxic drugs to cancer cells, offering a potential therapeutic strategy for bone metastases.