The Affiliated Stomatological Hospital of Nanchang University, Nanchang, People's Republic of China.
The Key Laboratory of Oral Biomedicine, Nanchang, People's Republic of China.
Int J Nanomedicine. 2022 Oct 12;17:4757-4772. doi: 10.2147/IJN.S375999. eCollection 2022.
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.
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).
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.
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.
基于纳米载体的治疗学向癌症治疗的转化受到其细胞摄取能力差、载药量低、药物释放不可控和成像能力不足的限制。
在这项研究中，通过用聚丙烯酸（PAA）修饰壳聚糖（CTS）/三聚磷酸酯（TPP）纳米颗粒（NPs），并进一步缀合半胱氨酸功能化的金纳米颗粒（AuNPs），制备了新型杂化纳米凝胶作为治疗学纳米载体。
所得的纳米凝胶，称为 CTS/TPP/PAA@AuNPs（CTPA），表现出优异的胶体稳定性和 87%的阳离子药物阿霉素（DOX）的高包封率。在肿瘤微环境中，酸性 pH 值和溶酶体的过表达触发 CTPA@DOX 降解并发出更小的纳米块（30-40nm），这些纳米块以肿瘤响应的方式顺序释放药物。细胞摄取实验表明 CTPA 促进了 DOX 进入细胞质。此外，通过 AuNP 介导的计算机断层扫描（CT）成像观察到，CTPA@DOX 能够在肿瘤中实现有利的积累。我们的体外和体内数据表明，CTPA 使 DOX 能够实现先进的肿瘤细胞靶向递药，其抗肿瘤活性和生物安全性均优于游离 DOX。
天然聚合物 CTS 被开发用于可降解纳米凝胶，可精确追踪具有高抗肿瘤活性的药物。此外，表面调整策略可以组装起来实现阳离子药物负载和高载药量、控制药物释放和足够的成像能力。因此，多功能 CTPA 能够实现高效的药物递送和 CT 成像，有望为设计先进的治疗学系统提供有价值的策略。
