N-trimethyl chitosan nanoparticle-encapsulated lactosyl-norcantharidin for liver cancer therapy with high targeting efficacy.
N-Trimethyl chitosan (TMC) was synthesized and used to prepare lactosyl-norcantharidin TMC nanoparticles (Lac-NCTD-TMC-NPs) using an ionic cross-linkage process. Lac-NCTD-TMC-NPs with an average particle size of 120.6 ± 1.7 nm were obtained, with an entrapment efficiency of 69.29% ± 0.76%, and a drug-loading amount of 9.1% ± 0.07%. The release of Lac-NCTD-TMC-NPs in vitro was investigated through a dialysis method, and its sustained effect was evident. In the human liver cancer cell line HepG2, the half-maximum inhibiting concentration (IC(50)) of TMC-encapsulated Lac-NCTD (Lac-NCTD-TMC-NPs) was only 24.2% that of free Lac-NCTD at 24 hours. Lac-NCTD induced HepG2 cell death by triggering apoptosis. In vitro cellular uptake and in vivo NIR fluorescence real-time imaging both indicated a high targeting efficacy. In comparison with Lac-NCTD and Lac-NCTD chitosan NPs (Lac-NCTD-CS-NPs ), Lac-NCTD-TMC-NPs had the strongest antitumor activity on the murine hepatocarcinoma 22 subcutaneous model.


BACKGROUND
In this article the preparation of N-trimethyl chitosan-encapsulated lactosyl-norcantharidin nanoparticles is described that displayed efficient targeting and sustained release in a hepatocarcinoma SC murine model.
Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, People's Republic of China.
Min
M
Guan
Yi
Y
Zhou
Qiao-Ling
QL
Zhu
Yang
Y
Liu
Yong-Yan
YY
Bei
Xue-Nong
XN
Zhang
Qiang
Q
Zhang
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry
D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; C118071:N-trimethyl chitosan chloride; C069741:norcantharidin; D048271:Chitosan