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Nanoparticle activated by near-IR delivers and cleaves Photo-Morpholino

Jayakumar MK, Bansal A, Huang K, Yao R, Li BN, Zhang Y. Near-Infrared-Light-Based Nano-Platform Boosts Endosomal Escape and Controls Gene Knockdown in Vivo. ACS Nano. 2014 Apr 14. [Epub ahead of print]

Nanoparticles of about 30 nm diameter were constructed based on β-NaYF4 crystals doped with Yb3+ and Tm3+ inside and Yb3+ and Er3+ in the shell. When illuminated with a 980nm IR laser, the particles emitted in the visible and UV bands. The particles were coated with mesoporous silica and loaded with TPPS2a (mesotetraphenylporphine with two sulfonate groups on adjacent phenyl rings) and Photo-Morpholino duplexes. The TPPS2a is a photosensitizer for photochemical internalization and the Photo-Morpholino duplexes consisted of antisense Morpholino targeting STAT3 and a complementary sense Photo-Morpholino strand to cage the antisense activity.

In B16F0 cells, which express STAT3, the STAT3 expression decreased to about 50% after incubation with nanoparticles and irradiation with the IR laser. Uptake was temperature dependent.

To set up a melanoma tumor model in mice, B16F0 cells were injected subcutaneously on day 0. Nanoparticles were injected day 5 and day 8 and tumors were irradiated with the IR laser. The treatment reduced the tumor volume relative to controls by about eightfold. The mice maintained their weight through the treatments.

I've skipped describing many controls and characterizations of materials. The bottom line is that their system delivered antisense activity to the IR-illuminated tumors. For more detail, see their fascinating paper.