Tumour microenvironment-responsive lipoic acid nanoparticles for targeted delivery of docetaxel to lung cancer.
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.
Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
Fenfen
F
Gu
Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
Chuling
C
Hu
Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
Zhongguang
Z
Tai
Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
Chong
C
Yao
Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
Jing
J
Tian
Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
Lijuan
L
Zhang
Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
Qingming
Q
Xia
Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
Chunai
C
Gong
Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.|Department of Clinical Pharmacy and Pharmaceutical Management, School of Pharmacy, Fudan University, Shanghai, 201203, China.
Yuan
Y
Gao
Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
Shen
S
Gao
D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008063:Thioctic Acid / Q000737:chemistry*; D016896:Treatment Outcome; D059016:Tumor Microenvironment / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D008063:Thioctic Acid