Tumour microenvironment-responsive lipoic acid nanoparticles for targeted delivery of docetaxel to lung cancer

• Published in: Scientific reports 2016-11, Vol.6 (1), p.36281, Article 36281
• Main Authors: Gu, Fenfen, Hu, Chuling, Tai, Zhongguang, Yao, Chong, Tian, Jing, Zhang, Lijuan, Xia, Qingming, Gong, Chunai, Gao, Yuan, Gao, Shen
• Format: Article
• Language: English
• Subjects: 13; 13/2; 13/31; 13/51; 14; 14/19; 14/34; 14/63; 59; 631/1647/350/354; 631/61/54/152; 631/67/327; 64; 64/60; A549 Cells; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Cancer; Cell Proliferation - drug effects; Cytotoxicity; Drug Delivery Systems - methods; Drug Liberation; Female; Humanities and Social Sciences; Humans; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Mice, Inbred BALB C; Mice, Nude; multidisciplinary; Nanoparticles; Nanoparticles - chemistry; Physicochemical properties; Science; Taxoids - administration & dosage; Taxoids - chemistry; Taxoids - pharmacokinetics; Thioctic Acid - chemistry; Treatment Outcome; Tumor microenvironment; Tumor Microenvironment - drug effects; Tumors; Xenograft Model Antitumor Assays; Zeta potential
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep36281

In the present study, we developed a novel type of reduction-sensitive nanoparticles (NPs) for docetaxel (DTX) delivery based on cross-linked lipoic acid NPs (LANPs). The physicochemical properties, cellular uptake and in vitro cytotoxicity of DTX loaded LANPs (DTX-LANPs) on A549 cells were investigated. Furthermore, the in vivo distribution and in vivo efficacy of DTX-LANPs was evaluated. The results showed that DTX-LANPs had a particle size of 110 nm and a negative zeta potential of −35 mv with excellent colloidal stability. LANPs efficiently encapsulated DTX with a high drug loading of 4.51% ± 0.49% and showed remarkable reduction-sensitive drug release in vitro . Cellular uptake experiments demonstrated that LANPs significantly increased intracellular DTX uptake by about 10 fold as compared with free DTX. The cytotoxicity of DTX-LANPs showed significantly higher potency in inhibiting A549 cell growth than free DTX, while blank LANPs had a good biocompatibility. In addition, in vivo experiments demonstrated that DTX-LANPs could enhance tumour targeting and anti-tumour efficacy with low systemic toxicity. In conclusion, LANPs may prove to be a potential tumour microenvironment-responsive delivery system for cancer treatment, with the potential for commercialization due to the simple component, controllable synthesis, stability and economy.