Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 12, Issue 24, Pages 26880-26892Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c03873
Keywords
nanocluster assembly; ultrasmall gold nanoparticles; tumor microenvironment response; blood-brain barrier; orthotopic glioma tumor
Funding
- Major State Basic Research Development Program of China [2017YFE0103600, 2017YFA0205201, 2018YFA0107301]
- National Natural Science Foundation of China [81422023, 81603015, 81871404, 81720108021, 81772009, 81641168, 31470047, U1705281, U1505221]
- Fundamental Research Funds for the Central Universities [20720190088]
- Scientific and Technological Research Project of Henan Province [182102310162]
- Zhongyuan Thousand Talents Plan Project-Basic Research Leader Talent [ZYQR201810117]
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Glioblastoma is one of the most lethal cancers and needs effective therapeutics. The development of coordination-driven metal-organic nanoassemblies, which can cross the blood- brain barrier (BBB) and blood-brain tumor barrier (BBTB) and have multiple desired functions, may provide a promising solution to this issue. Here, we report an in situ assembled nanoplatform based on RGD peptide-modified bisulfite-zinc(II)-dipicolylamineArg-Gly-Asp (Bis(DPA-Zn)-RGD) and ultrasmall Au-ICG nano-particles. Attributed to its positive charges and neovascular targeting properties, Bis(DPA-Zn)-RGD can be selectively delivered to the tumor site, and then assembled in situ into large nanoclusters with subsequently administered Au-ICG nanoparticles. Au nano-particles with ultrasmall size (similar to 7 nm) can successfully cross the BBB. The obtained nanoclusters exhibit strong near-infrared-red (NIR) absorption and an enhanced tumor retention effect, enabling precise orthotopic fluorescence/photoacoustic imaging. With the aid of image guidance, the photothermal effect of the nanoclusters is observed to suppress tumor progression with the inhibition efficiency reaching up to 93.9%. Meanwhile, no photothermal damage can be found for normal brain tissues. These results, herein, suggest a feasible nanotheranostic agent with the ability to overcome the BBB and BBTB for imaging and therapy of orthotopic brain tumors.
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