Ultrasound-mediated in vivo biodistribution of coumarin-labeled sorafenib-loaded liposome-based nanotheranostic system.

Aim: This study aimed to synthesize folate-conjugated sorafenib-loaded (FCSL) liposomes for theranostic application using ultrasound (US). Materials & methods: US parameter optimization, in vitro release, anticancer effect, in vivo biodistribution, optical imaging and biocompatibility of liposomes were studied. Results: With 84% in vitro release after 4 min of US exposure at 3 MHz (1.2 mechanical index), FCSL liposomes showed lower IC50 (8.70 µM) versus sorafenib (9.34 µM) against HepG2 cells. In vivo biodistribution of FCSL liposomes versus sorafenib after 9 mg/kg injection in the liver (8.63 vs 0.55) > intestine (8.45 vs 1.07) > stomach (5.62 vs 0.57) > kidney (5.46 vs 0.91) showed longer circulation time in plasma and can be tracked in mice. Conclusion: A threefold higher drug concentration in the liver in US-exposed mice makes this a successful nanotheranostic approach.

Sorafenib is the first-line treatment for liver cancer, but it has low absorption due to its poor water solubility and unavoidable side effects. Liposomes can encapsulate a wide range of diagnostic and therapeutic agents. Ultrasound (US) application can lead to enhanced penetration and release at the site of action. In this study, folate-ornamented sorafenib-loaded liposomes were evaluated for safe intravenous administration, anticancer effect, biodistribution and bioavailability in mice after US application. The results of this study will help researchers understand how US and optical imaging show that coumarin-labeled liposomes can act as theranostic agents with dual properties of therapeutics and imaging. US and folate-conjugated sorafenib-loaded theranostic liposomes can be utilized as a promising approach to cancer treatment.

Synthesis and expression of recombinant interferon alpha-5 gene in tobacco chloroplasts, a non-edible plant.

The production of interferon alpha from microbial to mammalian expression system, have certain precincts in terms of cost, scalability, safety and authenticity. Modern biotechnology exploits transgenic crops to get large quantities of complex proteins in a cost-effective way. In order to overcome several challenges from biosafety point of view, the chloroplast transformation strategy is one of the best approaches since plastids are strictly maternally inherited in most of the cultivated species. In the present study the interferon alpha 5 gene was synthesized by using complex set of oligos. After sequence confirmation of the synthesized gene, the histidine residues along with the thrombin protease site were engineered upstream to the synthetic interferon alpha 5 gene. The recombinant fragment was then tethered with chloroplast light inducible promoter, rbcl followed by sequential cloning to develop chloroplast transformation vector to target the cassette into the inverted repeat region of plastome through two events of homologous recombination. The putative transgenic plants obtained through biolistic delivery method and as a result of antibiotic selection of bombarded leaves, were subjected to different rounds of selection and regeneration for homoplasmicity. The spectinomycin-resistant shoots were analyzed through Polymerase Chain Reaction and Sothern blotting. The expression of introduced synthetic genes was recorded using Enzyme Linked ImmunoSorbant Assay technique. It was experienced that mature leaves contained comparatively high levels of interferon compared to young and senescence leaves.