Polyethylenimine-based theranostic nanoplatform for glioma-targeting single-photon emission computed tomography imaging
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Journal of Nanobiotechnology Open Access
RESEARCH
Polyethylenimine‑based theranostic nanoplatform for glioma‑targeting single‑photon emission computed tomography imaging and anticancer drug delivery Lingzhou Zhao1†, Jingyi Zhu2†, Jiali Gong1†, Ningning Song1, Shan Wu1, Wenli Qiao1, Jiqin Yang3*, Meilin Zhu4* and Jinhua Zhao1*
Abstract Background: Glioma is the deadliest brain cancer in adults because the blood–brain-barrier (BBB) prevents the vast majority of therapeutic drugs from entering into the central nervous system. The development of BBB-penetrating drug delivery systems for glioma therapy still remains a great challenge. In this study, we aimed to design and develop a theranostic nanocomplex with enhanced BBB penetrability and tumor-targeting efficiency for glioma single-photon emission computed tomography (SPECT) imaging and anticancer drug delivery. Results: This multifunctional nanocomplex was manufactured using branched polyethylenimine (PEI) as a template to sequentially conjugate with methoxypolyethylene glycol (mPEG), glioma-targeting peptide chlorotoxin (CTX), and diethylenetriaminepentaacetic acid (DTPA) for 99mTc radiolabeling on the surface of PEI. After the acetylation of the remaining PEI surface amines using acetic anhydride (Ac2O), the CTX-modified PEI (mPEI-CTX) was utilized as a carrier to load chemotherapeutic drug doxorubicin (DOX) in its interior cavity. The formed mPEI-CTX/DOX complex had excellent water dispersibility and released DOX in a sustainable and pH-dependent manner; furthermore, it showed targeting specificity and therapeutic effect of DOX toward glioma cells in vitro and in vivo (a subcutaneous tumor mouse model). Owing to the unique biological properties of CTX, the mPEI-CTX/DOX complex was able to cross the BBB and accumulate at the tumor site in an orthotopic rat glioma model. In addition, after efficient radiolabeling of PEI with 99mTc via DTPA, the 99mTc-labeled complex could help to visualize the drug accumulation in tumors of gliomabearing mice and the drug delivery into the brains of rats through SPECT imaging. Conclusions: These results indicate the potential of the developed PEI-based nanocomplex in facilitating gliomatargeting SPECT imaging and chemotherapy. Keywords: Polyethylenimine, Chlorotoxin, Drug delivery, SPECT imaging, Glioma *Correspondence: qin‑[email protected]; [email protected]; [email protected] † Lingzhou Zhao, Jingyi Zhu and Jiali Gong equally contributed to this work 1 Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People’s Republic of China 3 Department of Nuclear Medicine, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, People’s Republic of China 4 School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, People’s Republic of China Full list of author information is available at the end of the article
Background The diffuse invasion and infiltrative overgrowth of glioma cells lead to the development of
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