Design and Synthesis of Triazine-Based Hydrogel for Combined Targeted Doxorubicin Delivery and PI3K Inhibition.

IF 5.4 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Biomaterials Science & Engineering Pub Date : 2025-01-13 Epub Date: 2025-01-03 DOI:10.1021/acsbiomaterials.4c01291
Subhasis Mandal, Avinandan Bhoumick, Arpana Singh, Sukanya Konar, Arkajyoti Banerjee, Arnab Ghosh, Prosenjit Sen
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Abstract

Melanoma, an aggressive skin cancer originating from melanocytes, presents substantial challenges due to its high metastatic potential and resistance to conventional therapies. Hydrogels, 3D networks of hydrophilic polymers with high water-retention capacities, offer significant promise for controlled drug delivery applications. In this study, we report the synthesis and characterization of hydrogelators based on the triazine molecular scaffold, which self-assemble into fibrous networks conducive to hydrogel formation. Rheological analysis confirmed their hydrogelation properties, while microscopic techniques, including FE-SEM and FEG-TEM, provided insights into their morphological networks. The drug delivery capability of these hydrogelators was evaluated using doxorubicin, a widely employed anticancer agent, demonstrating enhanced biocompatibility and reduced side effects compared to free doxorubicin. Additionally, the hydrogelators exhibited inhibitory activity against phosphoinositide 3-kinase (PI3K), a key enzyme frequently mutated in cancer and also involved in melanoma progression. The dual functionality of this delivery system─controlled drug release and PI3K inhibition─highlights the potential of triazine-based hydrogelators as innovative therapeutic platforms for melanoma treatment.

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基于三嗪的阿霉素靶向递送和PI3K抑制联合水凝胶的设计与合成。
黑色素瘤是一种起源于黑色素细胞的侵袭性皮肤癌,由于其高转移潜力和对传统治疗的耐药性,提出了实质性的挑战。水凝胶是具有高保水能力的亲水性聚合物的3D网络,为控制药物输送应用提供了巨大的希望。在这项研究中,我们报道了基于三嗪分子支架的水凝胶剂的合成和表征,这种水凝胶剂可以自组装成有利于水凝胶形成的纤维网络。流变学分析证实了它们的水凝胶性质,而微观技术,包括FE-SEM和fg - tem,提供了对它们形态网络的见解。使用阿霉素(一种广泛使用的抗癌药物)对这些凝胶剂的药物传递能力进行了评估,与游离阿霉素相比,这些凝胶剂的生物相容性增强,副作用减少。此外,凝胶对磷酸肌肽3-激酶(PI3K)具有抑制活性,PI3K是癌症中经常突变的关键酶,也参与黑色素瘤的进展。这种递送系统的双重功能──控制药物释放和抑制PI3K──凸显了三嗪基凝胶剂作为黑色素瘤治疗的创新治疗平台的潜力。
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来源期刊
ACS Biomaterials Science & Engineering
ACS Biomaterials Science & Engineering Materials Science-Biomaterials
CiteScore
10.30
自引率
3.40%
发文量
413
期刊介绍: ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics: Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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