Abstract
Osteosarcoma (OS) is a rare and aggressive bone tumor that impacts mostly children and
young adults. In spite of the numerous efforts made to date in the therapeutic field, OS still
presents a low patient survival rate, high metastasis and relapse occurrence, mostly due to
multidrug resistant cells. To surpass that, nanomedicine has been extensively investigated for
the targeted delivery of genetic material, drugs or both. Polymeric micelles (PM) are
nanosystems that facilitate the targeted transportation of poorly water-soluble drugs to cancer
cells. These nanocomposites are composed of amphiphilic block copolymers, such as
poloxamers, or Pluronics®, that self-assemble into a micellar structure when in contact with an
aqueous solution. Pluronics® F68, and P123 are widely used poloxamers in the
pharmaceutical area due to their advantageous characteristics. A micelleplex is formed from
the interactions of cationic amphiphilic copolymers with genetic material and/or drugs.
Cationic components of micelleplexes can be of natural or synthetic origin, such as chitosan
or polyethyleneimine (PEI), respectively.
miRNAs have been implicated as participators in the development, metastasis and
progression of OS. miRNA-145 is underexpressed in this disease and associated with a worse
cancer prognosis. We hypothesize that the delivery of miRNA-145 to OS cells via a
micelleplex composed of Pluronic® F68 and either chitosan or PEI, will be able to inhibit
tumor proliferation and migration.
In this work, we aim to elucidate the application of a micelleplex encapsulating miRNA-145
in order to achieve a targeted delivery to OS cells and overcome multidrug resistance, as a
new and viable treatment option. As such, we have developed and optimized a mixed PM
consisting of Pluronics® P123 and F68 and cationic graft copolymer F68-PEI.
Keywords: Chitosan, Osteosarcoma, Micelleplex, miRNA-145, Pluronic® F68, Pluronic® P123, Polyethyleneimine, Polymeric Micelle.
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