Carboxymethyl chitosan-poly(amidoamine) dendrimer core-shell nanoparticles for intracellular lysozyme delivery.
Intracellular delivery of native, active proteins is challenging due to the fragility of most proteins. Herein, a novel polymer/protein polyion complex (PIC) nanoparticle with core-shell structure was prepared. Carboxymethyl chitosan-grafted-terminal carboxyl group-poly(amidoamine) (CM-chitosan-PAMAM) dendrimers were synthesized by amidation and saponification reactions. (1)H NMR was used to characterize CM-chitosan-PAMAM dendrimers. The TEM images and results of lysozyme loading efficiency indicated that CM-chitosan-PAMAM dendrimers could self-assemble into core-shell nanoparticles, and lysozyme was efficiently encapsulated inside the core of CM-chitosan-PAMAM dendrimer nanoparticles. Activity of lysozyme was completely inhibited by CM-chitosan-PAMAM Dendrimers at physiological pH, whereas it was released into the medium and exhibited a significant enzymatic activity in an acidic intracellular environment. Moreover, the CM-chitosan-PAMAM dendrimer nanoparticles did not exhibit significant cytotoxicity in the range of concentrations below 3.16 mg/ml. The results indicated that these CM-chitosan-PAMAM dendrimers have excellent properties as highly potent and non-toxic intracellular protein carriers, which would create opportunities for novel applications in protein delivery.
School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering of Ministry of Education, Tianjin University, Tianjin 300072, China.
Xiaoyang
X
Zhang
Jun
J
Zhao
Yan
Y
Wen
Chuanshun
C
Zhu
Jun
J
Yang
Fanglian
F
Yao
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D050091:Dendrimers / Q000138:chemical synthesis* / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000494:pharmacology; D004339:Drug Compounding; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009113:Muramidase / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011073:Polyamines / Q000737:chemistry*
D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; C531249:Poly(amidoamine); D011073:Polyamines; C514968:carboxymethyl-chitosan; D048271:Chitosan; D009113:Muramidase
Carboxymethyl chitosan; Core–shell nanoparticles; Intracellular lysozyme delivery; Poly (amidoamine) dendrimer; pH-sensitive