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转铁蛋白共轭的pH/近红外响应性黑磷纳米平台:一种用于乳腺癌诊疗的新型多模态方法。

Transferrin conjugated pH/NIR-responsive black phosphorus nanoplatform: A novel multimodal approach for breast cancer theranostics.

作者信息

Soman Soji, Kulkarni Sanjay, John Jeena, Paul Milan, Nandakumar Krishnadas, Biswas Swati, George Sajan D, Mutalik Srinivas

机构信息

Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.

Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.

出版信息

Int J Pharm X. 2025 Jul 22;10:100364. doi: 10.1016/j.ijpx.2025.100364. eCollection 2025 Dec.


DOI:10.1016/j.ijpx.2025.100364
PMID:40822245
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12356476/
Abstract

Cancer is one of the foremost causes of death, posing a significant challenge to global health. Breast cancer is predominant cancer type in women globally. Nanotheranostic platforms have emerged as a promising strategy for enhancing breast cancer therapy by integrating both diagnostic and therapeutic functionalities. Black phosphorous nanosheets (BPNSs) are nanotheranostic 2D materials that can adsorb a large number as well as quantity of therapeutic or theranostic agents due to their greater surface area. Herein, the authors developed an efficient pH and NIR-responsive nanotheranostic drug delivery platform for synergistic chemo/photothermal/photodynamic therapy of breast cancer. The exfoliated BPNSs were surface loaded with an anticancer drug, doxorubicin (DOX), functionalized with a photo-responsive polymer, polydopamine (PDA), and conjugated with a protein-based ligand, transferrin (TF). The prepared BP-based nanoformulation demonstrated excellent photothermal stability, improved targeting efficiency and desired therapeutic activity. A pH/NIR-responsive nature was observed during in vitro DOX release studies with negligible toxicity during hemolysis and CAM assay. Cell line studies on 4 T1 cells showed NIR-specific toxicity compared to non-irradiated groups with excellent ligand-mediated cellular uptake. Furthermore, an increase in the amount of necrotic and apoptotic cells in 4 T1 cells with elevated ROS levels were observed. 4 T1-tumour bearing BALB/c mice models administered with BP-based nanoformulation indicated an efficient reduction in tumour volume in NIR-irradiated groups and enhanced pharmacokinetic parameters. In vitro and in vivo studies demonstrated that the synergistic approach of merging chemotherapy with photothermal and photodynamic therapy exhibits remarkable antitumour effectiveness, excellent biocompatibility, and promising competence for clinical application.

摘要

癌症是主要的死亡原因之一,对全球健康构成重大挑战。乳腺癌是全球女性中最主要的癌症类型。纳米诊疗平台已成为一种有前景的策略,通过整合诊断和治疗功能来增强乳腺癌治疗效果。黑磷纳米片(BPNSs)是一种纳米诊疗二维材料,由于其较大的表面积,能够吸附大量的治疗或诊疗剂。在此,作者开发了一种高效的pH和近红外响应型纳米诊疗药物递送平台,用于乳腺癌的协同化疗/光热/光动力治疗。将剥离的BPNSs表面负载抗癌药物阿霉素(DOX),用光响应聚合物聚多巴胺(PDA)进行功能化,并与基于蛋白质的配体转铁蛋白(TF)共轭。所制备的基于BP的纳米制剂表现出优异的光热稳定性、提高的靶向效率和理想的治疗活性。在体外DOX释放研究中观察到pH/近红外响应特性,在溶血和鸡胚绒毛尿囊膜试验中毒性可忽略不计。对4T1细胞系的研究表明,与未照射组相比,近红外具有特异性毒性,且具有优异的配体介导的细胞摄取。此外,观察到4T1细胞中坏死和凋亡细胞数量增加,ROS水平升高。用基于BP的纳米制剂给药的荷4T1肿瘤BALB/c小鼠模型表明,近红外照射组的肿瘤体积有效减小,药代动力学参数增强。体外和体内研究表明,将化疗与光热和光动力治疗相结合的协同方法具有显著的抗肿瘤效果、优异的生物相容性和有前景的临床应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/88fbab25fa42/gr14.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/88fbab25fa42/gr14.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/0243ab340fd5/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/9d0d737d19e5/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/bfbd5a03403d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/17ea2aa0d7b4/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/8ec01805cb76/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/73997e2f8162/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/a571c7865b59/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/6237e1aebef2/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/224e748422b2/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/29d3be15b0d0/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/a9158f12b59a/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/e72d200b856f/gr11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/6eec70ce59bd/gr12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/e64ef40d31d9/gr13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b3/12356476/88fbab25fa42/gr14.jpg

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本文引用的文献

[1]
Biotinylated platinum(IV)-conjugated graphene oxide nanoparticles for targeted chemo-photothermal combination therapy in breast cancer.

Biomater Adv. 2025-3

[2]
Advanced 2D Nanomaterials for Phototheranostics of Breast Cancer: A Paradigm Shift.

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[3]
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Int J Pharm. 2024-11-15

[4]
Nano-Innovations in Cancer Therapy: The Unparalleled Potential of MXene Conjugates.

Materials (Basel). 2024-3-20

[5]
Black phosphorus quantum dots camouflaged with platelet-osteosarcoma hybrid membrane and doxorubicin for combined therapy of osteosarcoma.

J Nanobiotechnology. 2023-7-28

[6]
Macrophage-inherited exosome excise tumor immunosuppression to expedite immune-activated ferroptosis.

J Immunother Cancer. 2023-5

[7]
2D Hetero-Nanoconstructs of Black Phosphorus for Breast Cancer Theragnosis: Technological Advancements.

Biosensors (Basel). 2022-11-11

[8]
Levofloxacin in nanostructured lipid carriers: Preformulation and critical process parameters for a highly incorporated formulation.

Int J Pharm. 2022-10-15

[9]
Anticancer Drugs: Recent Strategies to Improve Stability Profile, Pharmacokinetic and Pharmacodynamic Properties.

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[10]
Characterization and targeting ability evaluation of cell-penetrating peptide LyP-1 modified alginate-based nanoparticles.

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