Proton-sponge coated quantum dots for siRNA delivery and intracellular imaging.
We report the rational design of multifunctional nanoparticles for short-interfering RNA (siRNA) delivery and imaging based on the use of semiconductor quantum dots (QDs) and proton-absorbing polymeric coatings (proton sponges). With a balanced composition of tertiary amine and carboxylic acid groups, these nanoparticles are specifically designed to address longstanding barriers in siRNA delivery such as cellular penetration, endosomal release, carrier unpacking, and intracellular transport. The results demonstrate dramatic improvement in gene silencing efficiency by 10-20-fold and simultaneous reduction in cellular toxicity by 5-6-fold, when compared directly with existing transfection agents for MDA-MB-231 cells. The QD-siRNA nanoparticles are also dual-modality optical and electron-microscopy probes, allowing real-time tracking and ultrastructural localization of QDs during delivery and transfection. These new insights and capabilities represent a major step toward nanoparticle engineering for imaging and therapeutic applications.
Yezhelyev
Maksym V
MV
Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA.
Qi
Lifeng
L
O'Regan
Ruth M
RM
Nie
Shuming
S
Gao
Xiaohu
X
D000818:Animals; D045744:Cell Line, Tumor; D021983:Cyclophilins / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors / Q000235:genetics; D011522:Protons; D045663:Quantum Dots; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry* / Q000235:genetics; D014162:Transfection / Q000379:methods*
D011522:Protons; D034741:RNA, Small Interfering; C081786:cyclophilin B; D021983:Cyclophilins; D019696:Peptidylprolyl Isomerase