Simultaneous nuclear imaging and intranuclear drug delivery by nuclear-targeted multifunctional upconversion nanoprobes.
Nuclear-targeted therapy by delivering anticancer drug directly into cancer cell nuclei can elicit synergistic therapeutic effects and kill these cancer cells with much enhanced efficiencies. Besides nuclear targeting, another difficulty in nuclear-targeted therapy is how to achieve real-time monitoring of the therapy process simultaneously. In this article we report on the development of multifunctional upconversion nanoparticles (UCNPs) which were able to target cancer cell nuclei, and thus deliver the anticancer drug directly to the nuclear region and simultaneously image cell nucleus by magnetic resonance (MR)/upconversion fluorescent for real-time guidance of their therapeutic action simultaneously. The Er/Yb-doped NaYF(4) core and NaGdF(4) shell endow the core/shell structured UCNPs with enhanced upconversion fluorescent imaging and more sensitive T(1)-MR imaging performances, and the surface conjugation of TAT peptide served as a key role in the nuclear targeting and nuclear transport process. This multifunctional UCNPs-based nano-theranostic was used to improve the efficacy of DOX in Hela humor tumor models, by direct DOX delivery to the nucleus under the synchronous monitoring of the nano-theranostics. Further development of this technology may provide more exciting opportunities in treating cancer disease by nuclear-targeted therapy.
State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China.
Jia-nan
JN
Liu
Wenbo
W
Bu
Li-min
LM
Pan
Shengjian
S
Zhang
Feng
F
Chen
Liangping
L
Zhou
Kuai-le
KL
Zhao
Weijun
W
Peng
Jianlin
J
Shi
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism*; D003287:Contrast Media / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy*; D019301:Oleic Acid / Q000737:chemistry; D010455:Peptides / Q000737:chemistry
D000970:Antineoplastic Agents; D003287:Contrast Media; D010455:Peptides; D019301:Oleic Acid; D004317:Doxorubicin