| Summary: | 1 In the proposed work, we planned to develop a novel liposomal paclitaxel formulation in PEGylated liposome conjugated with PCSK9 (PCSK9-PEGLip; PCSK9 conjugated Liposomes). Here we expected to combine the LDL-targeting properties of PCSK9 with the drug delivery properties of sterically stabilized liposomes. Therefore, our approach offered the dual benefit of localized delivery for the treatment of hepatocellular and other LDLR expressing carcinoma. This approach also helps us to address encapsulation of poorly soluble and acid-labile drugs, thus allowing them to reach their full therapeutic potential as anti-cancer agents. We first prepared PEGylated liposomes using previously described methods and these were used as controls for comparing with PCSK9-PEGLip (PCSK9 Conjugated Liposomes). Later PCSK9-PEGLips were prepared . We hypothesize that PCSK9-PEGLips (PCSK9 Conjugated Liposomes) will bind selectively to LDLR and thus form a targeting platform for cells with high LDLR expression. The elevated LDLR expression on tumor cells and the high LDLR expression on hepatocytes support the rationale for targeted drug delivery using polymer systems linked with PCSK9. This may by default be liver cells, but if the cancer is in another site on the body, enrichment at tumor will be achieved via the EPR effects. To date and to our knowledge, no attempt has been made to develop PCSK9-PEGLip formulations for targeting cancer. In this multidisciplinary project our team at Pontificia Universidad Católica de Chile (PUC) manufactured PCSK9-PEGLips, for physical characterization and in vitro testing in different cell lines. PARCIAL Unfortunately, the pandemic situation didn´t allow me to complete this in vivo assay because the lack of availability of animals. Moreover, my postdoc finished, and I had to look for another source of work (salary) to maintain my family. Furthermore, I completed the manuscript related (entirely) to the present project and it was accepted and published in an important journal (Biomedicine & ...
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