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Deep tumor-penetrating nano-delivery strategy to improve diagnosis and therapy in patient-derived xenograft (PDX) oral cancer model and patient tissue

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Abstract

Nanoprodrugs that are directly assembled by prodrugs attract considerable attention with high anticancer potentials. However, their stability and efficiency of tumor-targeted delivery remain a major challenge in practical biomedical applications. Here, we report a new deep tumor-penetrating nano-delivery strategy to achieve enhanced anti-cancer performance by systematic optimization of a porphyrin-doxorubicin-based nanoprodrug using various PEGylations/crosslinks and co-administration of targeting peptide iRGD. Polyethylene glycols (PEGs) with different molecular weights and grafts are employed to crosslink the nanoprodrug and optimize size, charge, tumor accumulation and penetration, and anti-cancer efficiency, etc. The tumor penetration was validated in syngeneic oral cancer mouse models, patient-derived xenograft (PDX) models, and oral cancer tissue from patients. The optimized nanoprodrug co-administrated with iRGD remarkably enhances the accumulation and penetration both in tumor vascular and PDX tumor tissue. It is effective and safe to improve in vivo therapeutic efficacy via the passive tumor targeting dependent and independent mode. Our tumor-penetrating nano-delivery strategy is promising to strengthen the nanoprodrugs in clinical implementation.

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Acknowledgements

The financial of this work was supported by National Institutes of Health/National Cancer Institute (Nos. R01CA199668 and R01CA232845), National Institutes of Health/National Institute of Dental and Craniofacial Research (No. 1R01DE029237), National Institutes of Health/ National Institute of Biomedical Imaging and Bioengineering (No. 9R01EB033677-06A1), UC Davis Comprehensive Cancer Center Support Grant (CCSG) awarded by the National Cancer Institute (No. NCI P30CA093373).

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Authors and Affiliations

  1. State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Longmeng Li & Yikai Zhou

  2. Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, 2700 Stockton Blvd, Sacramento, California, 95817, USA

    Longmeng Li, Aaron R. Lindstrom, Menghuan Tang, Bai Xiang, Xiangdong Xue & Yuanpei Li

  3. Department of Otolaryngology-Head and Neck Surgery, University of California Davis, 2521 Stockton Blvd, Sacramento, California, 95817, USA

    Andrew C. Birkeland

  4. Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California Davis, 2700 Stockton Blvd, Sacramento, California, 95817, USA

    Tzu-Yin Lin

  5. Key Laboratory of Hebei Province for Innovative drug research and evaluation, School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, 050017, China

    Bai Xiang

  6. School of Pharmacy, Pharm-X Center, Shanghai Jiao Tong University, Shanghai, 200240, China

    Xiangdong Xue

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  1. Longmeng Li
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  9. Yuanpei Li
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Correspondence to Yikai Zhou, Bai Xiang, Xiangdong Xue or Yuanpei Li.

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Deep tumor-penetrating nano-delivery strategy to improve diagnosis and therapy in patient-derived xenograft (PDX) oral cancer model and patient tissue

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Li, L., Lindstrom, A.R., Birkeland, A.C. et al. Deep tumor-penetrating nano-delivery strategy to improve diagnosis and therapy in patient-derived xenograft (PDX) oral cancer model and patient tissue. Nano Res. 16, 2927–2937 (2023). https://doi.org/10.1007/s12274-022-5047-2

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