Abstract
In the past few years, we have demonstrated the efficacy of a nanoparticle system, super carbonate apatite (sCA), for the in vivo delivery of siRNA/miRNA. Intravenous injection of sCA loaded with small RNAs results in safe, high tumor delivery in mouse models. To further improve the efficiency of tumor delivery and avoid liver toxicity, we successfully developed an inorganic nanoparticle device (iNaD) via high-frequency ultrasonic pulverization combined with PEG blending during the production of sCA. Compared to sCA loaded with 24 μg of miRNA, systemic administration of iNaD loaded with 0.75 μg of miRNA demonstrated similar delivery efficiency to mouse tumors with little accumulation in the liver. In the mouse therapeutic model, iNaD loaded with 3 μg of the tumor suppressor small RNA MIRTX resulted in an improved anti-tumor effect compared to sCA loaded with 24 μg. Our findings on the bio-distribution and therapeutic effect of iNaD provide new perspectives for future nanomedicine engineering.
Highlights
Cancer is the second leading cause of death, with an estimated 18.1 million new cancer cases and 9.6 million deaths in 2018 worldwide [1]
With bio-distribution imaging and anti-tumor effects, we show that the inorganic nanoparticle device (iNaD) results in less accumulation in normal tissues while highly improving tumor delivery efficiency compared to super carbonate apatite (sCA)
We had anticipated that smaller particles (
Summary
Cancer is the second leading cause of death, with an estimated 18.1 million new cancer cases and 9.6 million deaths in 2018 worldwide [1]. Systemic administration of engineered nanoparticles provides an opportunity to deliver reagents more precisely to tumor tissues, reducing the toxicity to normal organs and enhancing the anti-cancer effects compared to incorporated reagents alone. RNA delivery methods, such as liposomes and micelles, our sCA system has been recognized as a new inorganic nanoparticle for siRNA/miRNA [22,23,24,25]. To further improve the pulverization efficiency, we applied poly(ethylene glycol) (PEG) blending during sCA production, followed by pulverization This approach produced a new size of nanoparticles, 600–700 nm. With bio-distribution imaging and anti-tumor effects, we show that the iNaD results in less accumulation in normal tissues while highly improving tumor delivery efficiency compared to sCA. Our findings provide new insights for engineering nanomedicines
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