(2026) 3D printed, biodegradable, and biocompatible intraperitoneal implants loaded with folic acid-targeted/pH-sensitive/doxorubicin-loaded hydroxyapatite nanoparticles for systemic treatment of metastatic breast cancer. Journal of Nanobiotechnology. ISSN 14773155 (ISSN)
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Abstract
Three-dimensional porous scaffolds with the capability of controlled drug release have gained increasing interest in chemotherapy due to their sustained release of drugs and ability to reduce systemic toxicity. In this study, we advanced this concept by incorporating drug-loaded nanocarriers into 3D-printed scaffolds, creating trackable constructs for medical imaging such as CT-scan. Doxorubicin-loaded/folic acid-targeted pH-sensitive nanohydroxyapatite (Dox@nHA-FA) were synthesized and incorporated into gelatin/polycaprolactone/hydroxyapatite (Gel/PCL/HA) scaffolds via 3D printing. The Gel/PCL/HA(Dox@HA-FA) scaffolds were extensively characterized for drug release, mechanical strength, microstructure, and degradation profile. In vivo, scaffolds with different compositions were implanted in tumor-bearing Balb/c mice, and their degradation was monitored by CT-scan. The optimized scaffold composition shown medium disintegration tendency within 14 days and superior handling properties. In the orthotopic breast cancer model, Gel/PCL/HA(Dox@HA-FA) scaffolds produced a 71.8 reduction in tumor volume compared with untreated controls (P < 0.01), a 63.0 reduction versus free Dox (P < 0.05), and a 41.5 reduction versus Dox@HA-FA nanoparticles (P < 0.05). In addition, the number of metastatic liver colonies was reduced by ~65 compared with free Dox and by ~48 compared with Dox@HA-FA (P < 0.05). In the diffuse peritoneal metastasis model, Gel/PCL/HA(Dox@HA-FA) scaffolds led to a significant reduction (> 70, P < 0.01) in peritoneal metastatic nodules, whereas the other groups showed widespread dissemination. Biocompatibility was confirmed by histopathology and blood biochemistry, with no significant alterations in liver or kidney function markers compared with healthy controls (P > 0.05). Importantly, the scaffolds’ radio-opaque properties enabled non-invasive CT monitoring of degradation. Together, these results demonstrate that Gel/PCL/HA(Dox@HA-FA) scaffolds provide dual-targeted, sustained drug delivery with significant anti-tumor and anti-metastatic efficacy in vivo, supporting their potential for translation into local chemotherapy of advanced cancers. © The Author(s) 2025.
| Item Type: | Article |
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| Keywords: | 3D-printed porous scaffold Biodegradable scaffolds Cancer Nanostructured hydroxyapatite Animals Biocompatible Materials Breast Neoplasms Cell Line, Tumor Doxorubicin Drug Liberation Durapatite Female Folic Acid Humans Hydrogen-Ion Concentration Mice Mice, Inbred BALB C Nanoparticles Polyesters Printing, Three-Dimensional Tissue Scaffolds Biocompatibility Chemotherapy Controlled drug delivery Diseases Disintegration Drug products Mammals Nanocomposites Pathology Scaffolds Scaffolds (biology) Targeted drug delivery Toxicity Tumors 3 aminopropyltriethoxysilane acetic acid alanine aminotransferase amide anthracycline aspartate aminotransferase benzene calcium carbon chitosan creatinine dimethyl sulfoxide gelatin hydroxyapatite ketone molecular scaffold nanocarrier nanoparticle nitrogen oxygen phosphorus polycaprolactone three dimensional printed gel polycaprolactone hydroxyapatite nanoparticle scaffold unclassified drug biomaterial polyester reductions Biodegradable scaffold CT-scan Folic acids pH sensitive Porous scaffold 4T1 cell line animal cell animal experiment animal model animal tissue antineoplastic activity Article Barrett Joyner Halenda method biochemistry biodegradation Brunauer Emmett Teller method cancer chemotherapy cell culture cell viability cell viability assay computer assisted tomography contact angle controlled study cytotoxicity drug delivery system drug release elasticity elemental analysis encapsulation energy dispersive X ray spectroscopy field emission scanning electron microscopy histopathology HT-29 cell line human human cell HUVEC cell line hydrogen bond hydrophilicity in vitro study laparotomy liver function test MCF-7 cell line mechanical test metastatic breast cancer mouse MTT assay nonhuman particle size peritoneum metastasis photon correlation spectroscopy pore size static electricity stress strain relationship surface area surface charge swelling thermogravimetry thermostability three dimensional bioprinting tumor growth tumor volume ultraviolet visible spectrophotometry urea nitrogen blood level water solubility wettability X ray powder diffraction Young modulus zeta potential animal Bagg albino mouse breast tumor chemistry drug therapy pH three dimensional printing tissue scaffold tumor cell line |
| Journal or Publication Title: | Journal of Nanobiotechnology |
| Journal Index: | Scopus |
| Volume: | 24 |
| Number: | 1 |
| Identification Number: | https://doi.org/10.1186/s12951-025-03854-5 |
| ISSN: | 14773155 (ISSN) |
| Depositing User: | خانم ناهید ضیائی |
| URI: | http://eprints.mui.ac.ir/id/eprint/34801 |
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