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Tumor-Anchoring Drug-Loaded Fibrous Microspheres for MR Imaging-Guided Local Chemotherapy and Metastasis Inhibition

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Abstract

Unobtrusive metastasis and invasion of malignant tumors are major causes for the death of cancer patients, and unfortunately the lack of specificity and abrupt release of anticancer drugs applied to the primary tumors are causing serious side effects in cancer management. Hence, the development of controlled local drug delivery systems that can effectively treat primary tumors and inhibit tumor metastasis is of critical importance for improved cancer therapeutics. Herein, we developed hyaluronic acid (HA)-modified porous fibrous microspheres as a drug delivery system with the functions of long-acting local chemotherapy, tumor metastasis inhibition and magnetic resonance (MR) imaging. Poly (lactic-co-glycolic acid) (PLGA) short fibers obtained by combined electrospinning and homogenization techniques were successfully modified with gadolinium (Gd3+) chelates and HA, which were subsequently mixed with doxorubicin (DOX) to obtain the multifunctional drug-loaded fibrous microspheres of DOX-PLGA-PEI-DTPA-Gd/HA (DOX − PGH) by electrospray and further crosslinking. The developed DOX − PGH microspheres with an average diameter of 118.8 μm possess good structural stability and a high r1 relaxivity, and can achieve long-term DOX release. The cellular and animal experiments demonstrated that the DOX − PGH microspheres could facilitate targeted delivery of DOX to accelerate 4T1 cell death while reducing cancer cell metastasis due to the cooperative actions of long-term DOX-mediated chemotherapy and the fibrous microsphere-induced tumor anchoring to likely avoid primary tumor cell shedding, and render MR imaging of tumors during the treatment. The developed DOX − PGH microspheres may represent one of the updated local tumor chemotherapy formulations for improved tumor therapy with justified antitumor and anti-metastasis efficacy.

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Acknowledgements

Financial supports from the National Natural Science Foundation of China (81761148028 and 21773026), the Science and Technology Commission of Shanghai Municipality (19XD1400100, 20520710300, 21490711500, and 20DZ2254900), the Shanghai Education Commission through the Shanghai Leading Talents Program, and the 111 Project (BP0719035) are gratefully acknowledged. This work was also supported by FCT-Fundação para a Ciência e a Tecnologia through the CQM Base Fund - UIDB/00674/2020, and Programmatic Fund - UIDP/00674/2020, and by ARDITI-Agência Regional para o Desenvolvimento da Investigação Tecnologia e Inovação, through the project M1420-01-0145-FEDER-000005 - Centro de Química da Madeira - CQM+ (Madeira 14-20 Program).

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Authors and Affiliations

  1. State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, China

    Beilei Zhang, Yue Gao, Rui Yang, Zhijun Ouyang, **angyang Shi & Mingwu Shen

  2. CQM-Centro de Quimica da Madeira, Universidade da Madeira, 9020-105, Funchal, Portugal

    **angyang Shi

  3. Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China

    Hongwei Yu & Han Wang

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  1. Beilei Zhang
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  2. Yue Gao
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  3. Rui Yang
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  5. Hongwei Yu
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  6. Han Wang
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  7. **angyang Shi
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  8. Mingwu Shen
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Correspondence to **angyang Shi or Mingwu Shen.

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Zhang, B., Gao, Y., Yang, R. et al. Tumor-Anchoring Drug-Loaded Fibrous Microspheres for MR Imaging-Guided Local Chemotherapy and Metastasis Inhibition. Adv. Fiber Mater. 4, 807–819 (2022). https://doi.org/10.1007/s42765-022-00137-8

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