Sunday, August 8, 2021

131I-Labeled Multifunctional Polyethylenimine/Doxorubicin Complexes with pH-Controlled Cellular Uptake Property for Enhanced SPECT Imaging and Chemo/Radiotherapy of Tumors

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Int J Nanomedicine. 2021 Jul 30;16:5167-5183. doi: 10.2147/IJN.S312238. eCollection 2021.

ABSTRACT

INTRODUCTION: Smart theranostic nanosystems own a favorable potential to improve internalization within tumor while avoiding nonspecific interaction with normal tissues. However, development of this type of theranostic nanosystems is still a challenge.

METHODS: In this study, we developed the iodine-131 (131I)-labeled multifunctional polyethylenimine (PEI)/doxorubicin (DOX) complexes with pH-controlled cellular uptake property for enhanced single-photon emission computed tomography (SPECT) imaging and chemo/radiotherapy of tumors. Alkoxyphenyl acylsulfonamide (APAS), a typical functional group that could achieve improved cellular uptake of its modified nanoparticles, was utilized to conjugate onto the functional PEI pre-modified with polyethylene glycol (PEG) with terminal groups of monomethyl ether and N-hydroxysuccinimide (mPEG-NHS), PEG with terminal groups of maleimide and succinimidyl valerate (MAL-PEG-SVA) through sulfydryl of APAS and MAL moiety of MAL-PEG-SVA. This was followed by conjugation with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO), acetylating leftover amines of PEI, complexing DOX and labeling 131I to generate the theranostic nanosystems.

RESULTS: The synthesized theranostic nanosystems exhibit favorable water solubility and stability. Every functional PEI can complex approximately 12.4 DOX, which could sust ainably release of DOX following a pH-dependent manner. Remarkably, due to the surface modification of APAS, the constructed theranostic nanosystems own the capacity to achieve pH-responsive charge conversion and further lead to improved cellular uptake in cancer cells under slightly acidic condition. Above all, based on the coexistence of DOX and radioactive 131I in the single nanosystem, the synthesized nanohybrid system could afford enhanced SPECT imaging and chemo/radioactive combination therapy of cancer cells in vitro and xenografted tumor model in vivo.

DISCUSSION: The developed smart nanohybrid system provides a novel strategy to improve the tumor theranostic efficiency and may be applied for different types of cancer.

PMID:34354350 | PMC:PMC8331118 | DOI:10.2147/IJN.S312238

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