Self-assembled injectable Icariin@ Ti <sub>3</sub>C <sub>2</sub>Tx/doxorubicin hydrogel preserving osteogenesis while synergizing photodynamic and chemodynamic therapy for osteosarcoma

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Abstract

Local therapy involving injectable hydrogel systems loaded with doxorubicin (DOX) has garnered significant attention in the realm of osteosarcoma (OS) research. Nevertheless, it has been noted that the local delivery of high-dose DOX exerts a pronounced inhibitory impact on osteogenesis, which is detrimental to the restoration of functional capabilities after OS treatment. To address this challenge, we have designed a self-assembled injectable hydrogel system that integrates photodynamic and chemodynamic therapy, aiming to enhance efficacy while mitigating adverse effects on osteogenic differentiation. In this study, an injectable sodium alginate (SA) hydrogel was fabricated by encapsulating titanium carbide powder (Ti ₃C ₂Tx) and osteoprotegerin Icariin (ICA) along with DOX. This hydrogel system demonstrated remarkable drug-loading capacity and sustained drug release. Furthermore, under near-infrared (NIR) irradiation, the hydrogel displayed outstanding photothermal effects, which, in conjunction with chemotherapy and phototherapy, effectively eradicated UMR-106 tumor cells in vitro. The incorporation of ICA not only enhanced the anti-tumor effect but also alleviated the adverse effects of DOX on the osteogenic differentiation inhibition of bone marrow mesenchymal stem cells (BMSCs). In vivo, findings further confirmed that injectable ITD/SA hydrogels can synergistically heighten anti-osteosarcoma effectiveness while mitigating local osteogenic toxicity. Given these benefits, this hydrogel holds extensive application prospects in the local therapy of OS.

Graphical Abstract

Schematic diagram of injectable NIR-responsive ITD/SA hydrogel phototherapy versus chemotherapy for OS and protection against BMSCS. (A) Illustration of the preparation process of the ITD/SA hydrogel. (B) Schematic of the therapeutic effect of ITD/SA under NIR irradiation.

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MXene Ti3C2: An Effective 2D Light-to-Heat Conversion Material

Peng Wang, Renyuan Li, Lianbin Zhang … (2017)

MXene, a new series of 2D material, has been steadily advancing its applications to a variety of fields, such as catalysis, supercapacitor, molecular separation, electromagnetic wave interference shielding. This work reports a carefully designed aqueous droplet light heating system along with a thorough mathematical procedure, which combined leads to a precise determination of internal light-to-heat conversion efficiency of a variety of nanomaterials. The internal light-to-heat conversion efficiency of MXene, more specifically Ti3C2, was measured to be 100%, indicating a perfect energy conversion. Furthermore, a self-floating MXene thin membrane was prepared by simple vacuum filtration and the membrane, in the presence of a rationally chosen heat barrier, produced a light-to-water-evaporation efficiency of 84% under one sun irradiation, which is among the state of art energy efficiency for similar photothermal evaporation system. The outstanding internal light-to-heat conversion efficiency and great light-to-water evaporation efficiency reported in this work suggest that MXene is a very promising light-to-heat conversion material and thus deserves more research attention toward practical applications.

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Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Moderate to Severe Atopic Dermatitis : A Phase 3 Randomized Clinical Trial

Eric Simpson, Amy Paller, Elaine C. Siegfried … (2019)

Question What is the efficacy and safety of dupilumab monotherapy in adolescents with moderate to severe inadequately controlled atopic dermatitis? Findings In this randomized phase 3 clinical trial including 251 adolescents with moderate to severe atopic dermatitis, dupilumab 200 or 300 mg every 2 weeks and 300 mg every 4 weeks resulted in a significant treatment response vs placebo following 16-week treatment, with an acceptable safety profile. Meaning The findings appear to support the use of dupilumab for the treatment of adolescents with moderate to severe atopic dermatitis. Importance Adolescents with atopic dermatitis (AD) have high disease burden negatively affecting quality of life, with limited treatment options. The efficacy and safety of dupilumab, a monoclonal antibody, approved for treatment in adolescent patients with inadequately controlled AD, remain unknown in this patient population. Objective To assess the efficacy and safety of dupilumab monotherapy in adolescents with moderate to severe inadequately controlled AD. Design, Setting, and Participants A randomized, double-blind, parallel-group, phase 3 clinical trial was conducted at 45 US and Canadian centers between March 21, 2017, and June 5, 2018. A total of 251 adolescents with moderate to severe AD inadequately controlled by topical medications or for whom topical therapy was inadvisable were included. Interventions Patients were randomized (1:1:1; interactive-response system; stratified by severity and body weight) to 16-week treatment with dupilumab, 200 mg (n = 43; baseline weight <60 kg), or dupilumab, 300 mg (n = 39; baseline weight ≥60 kg), every 2 weeks; dupilumab, 300 mg, every 4 weeks (n = 84); or placebo (n = 85). Main Outcomes and Measures Proportion of patients with 75% or more improvement from baseline in Eczema Area and Severity Index (EASI-75) (scores range from 0 to 72, with higher scores indicating greater severity) and Investigator’s Global Assessment (IGA) 0 or 1 on a 5-point scale (scores range from 0 to 4, with higher scores indicating greater severity) at week 16. Results A total of 251 patients were randomized (mean [SD] age, 14.5 [1.7] years; 148 [59.0%] male). Of 250 patients with data available on concurrent allergic conditions, most had comorbid type 2 diseases (asthma, 134 [53.6%]; food allergies, 60.8%; allergic rhinitis, 65.6%). A total of 240 patients (95.6%) completed the study. Dupilumab achieved both coprimary end points at week 16. The proportion of patients with EASI-75 improvement from baseline increased (every 2 weeks, 41.5%; every 4 weeks, 38.1%; placebo, 8.2%) with differences vs placebo of 33.2% (95% CI, 21.1%-45.4%) for every 2 weeks and 29.9% (95% CI, 17.9%-41.8%) for every 4 weeks ( P < .001). Efficacy of the every-2-week regimen was generally superior to the every-4-week regimen. Patients in the dupilumab arms had higher percentage values of conjunctivitis (every 2 weeks, 9.8%; every 4 weeks, 10.8%; placebo, 4.7%) and injection-site reactions (every 2 weeks, 8.5%; every 4 weeks, 6.0%; placebo, 3.5%), and lower nonherpetic skin infections (every 2 weeks, 9.8%; every 4 weeks, 9.6%; placebo, 18.8%). Conclusions and Relevance In this study, dupilumab significantly improved AD signs, symptoms, and quality of life in adolescents with moderate to severe AD, with an acceptable safety profile. Placebo-corrected efficacy and safety of dupilumab were similar in adolescents and adults. Trial Registration ClinicalTrials.gov identifier: NCT03054428 This phase 3 randomized clinical trial evaluates the efficacy and safety of 2 dose regimens of dupilumab for treatment of moderate to severe atopic dermatitis in adolescents.

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Near-infrared light control of bone regeneration with biodegradable photothermal osteoimplant

Liping Tong, Qing Liao, Yuetao Zhao … (2019)

Mild heat stimulation can promote the restoration of bone defects but unfortunately, the delivery of exo-hyperthermy into human body is not efficient enough. In this study, mild heat-induced osteogenesis with high efficacy is demonstrated on an osteoimplant composed of black phosphorus nanosheets and poly(lactic-co-glycolic acid) (BPs@PLGA) with the participation of near-infrared (NIR) light irradiation. BPs@PLGA with only 0.2 wt% BPs show the highly-efficient NIR photothermal response even when being covered by a biological tissue as thick as 7 mm. In addition, this composite is completely biodegradable and the final degradation products are harmless H2O, CO2 and PO43- which can serve as necessary bone ingredient. The BPs@PLGA specimen mediated by low intensity and periodic NIR irradiation can effectively up-regulate the expressions of heat shock proteins and finally promote osteogenesis in vitro and in vivo. Boasting good biodegradability and NIR-mediated osteogenetic performances, the BPs@PLGA implant has great potential in orthopedic applications and this study provides new insights into the design and fabrication of new-style osteoimplants which can be remotely controlled.

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Author and article information

Contributors

Xin Liu: liuxinsurg@163.com

Bin Du: fsyy00608@njucm.edu.cn

Guangquan Sun: sunguangquan1981@163.com

Journal

Journal ID (nlm-ta): J Mater Sci Mater Med

Journal ID (iso-abbrev): J Mater Sci Mater Med

Title: Journal of Materials Science. Materials in Medicine

Publisher: Springer US (New York )

ISSN (Print): 0957-4530

ISSN (Electronic): 1573-4838

Publication date (Electronic): 15 March 2025

Publication date PMC-release: 15 March 2025

Publication date (Print): 2025

Volume: 36

Issue: 1

Electronic Location Identifier: 28

Affiliations

[1 ]Affiliated Hospital of Nanjing University of Chinese Medicine, ( https://ror.org/04523zj19) Nanjing, Jiangsu China

[2 ]Department of Orthopaedics, Jiangsu Provincial Hospital of Traditional Chinese Medicine, ( https://ror.org/05sm6p196) Nanjing, Jiangsu China

[3 ]School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, ( https://ror.org/00xp9wg62) Nanjing, Jiangsu China

Article

Publisher ID: 6874

DOI: 10.1007/s10856-025-06874-7

PMC ID: 11910421

PubMed ID: 40088393

SO-VID: a4073e60-2b1a-4541-b0c2-096ba9fd063e

License:

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

History

Date received : 29 November 2024

Date accepted : 20 February 2025

Funding

Funded by: FundRef https://doi.org/10.13039/http://dx.doi.org/10.13039/501100011407, Key Laboratory of Jiangsu Province for Chemical Pollution Control and Resources Reuse;

Award ID: JSDW202252

Award Recipient : Bin Du

Funded by: FundRef https://doi.org/10.13039/http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 82074471

Award Recipient : Bin Du

Funded by: FundRef https://doi.org/10.13039/, Science and Technology Development Programme Project of Jiangsu Provincial Administration of Traditional Chinese Medicine;

Award ID: MS2023023

Award Recipient : Guangquan Sun

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ScienceOpen disciplines: Materials science

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