Gold Nanoparticle-Incorporated Chitosan Nanogels as a Theranostic Nanoplatform for CT Imaging and Tumour Chemotherapy

Zhe Liu,1– 3,* Dong Zhou,4,* Xuan Yan,1 Lan Xiao,5,6 Pei Wang,1– 3 Junchao Wei,1– 4 Lan Liao1– 3 1The Affiliated Stomatological Hospital of Nanchang University, Nanchang, People’s Republic of China; 2The Key Laboratory of Oral Biomedicine, Nanchang, People’s Republic of China; 3Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, People’s Republic of China; 4School of Chemistry and Chemical Engineering, Nanchang University, Nanchang, People’s Republic of China; 5School of Mechanical, Medical & Process Engineering, Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, Australia; 6Australia China Centre for Tissue Engineering and Regenerative Medicine, Kelvin Grove, Brisbane, Australia*These authors contributed equally to this workCorrespondence: Junchao Wei; Lan Liao, Email weijunchao@ncu.edu.cn; Liaolan5106@ncu.edu.cnPurpose: The translation of nanocarrier-based theranostics into cancer treatment is limited by their poor cellular uptake, low drug-loading capacity, uncontrolled drug release, and insufficient imaging ability.Methods: In this study, novel hybrid nanogels were fabricated as theranostic nanocarriers by modifying chitosan (CTS)/tripolyphosphate (TPP) nanoparticles (NPs) with polyacrylic acid (PAA) and further conjugating cysteine-functionalized gold nanoparticles (AuNPs).Results: The resultant nanogels, referred to as CTS/TPP/PAA@AuNPs (CTPA), exhibited excellent colloidal stability and a high encapsulation rate of 87% for the cationic drug doxorubicin (DOX). In the tumour microenvironment, the acidic pH and overexpression of lysozyme triggered CTPA@DOX to degrade and emit smaller nanoblocks (30– 40 nm), which sequentially released the drug in a tumour-responsive manner. Cellular uptake experiments demonstrated that CTPA facilitates the entry of DOX into the cytoplasm. Furthermore, as visualised through AuNP-mediated computed tomography (CT) imaging, CTPA@DOX enabled favourable accumulation in the tumour. Our in vitro and in vivo data demonstrated that CTPA enabled advanced tumour cell-targeting delivery of DOX, which showed greater anti-tumour activity and biosafety than free DOX.Conclusion: The natural polymer CTS was developed for degradable nanogels, which can precisely track drugs with high antitumour activity. Additionally, the surface adjustment strategy can be assembled to achieve cationic drug loading and high drug-loading capacity, controlled drug release, and sufficient imaging ability. Therefore, multifunctional CTPA enables efficient drug delivery and CT imaging, which is expected to provide a valuable strategy for designing advanced theranostic systems.Keywords: theranostic nanomaterial, degradability, computed tomography imaging, hybrid nanogel