Nanobombs to Target Cancer Stem Cells

 

Conventional cancer therapies focus on eradicating the differentiated or differentiating cells in the tumour mass. While these form the bulk of the tumour, a small mass of cells known as the ‘cancer stem cells (CSCs)’ are often responsible for tumour relapse.

CSCs with the characteristics of normal stem cells, can give rise new cancer cells. Thus complete removal of CSCs is essential to achieve tumour regression. However CSCs are resistant to conventional chemotherapies and certain single stranded, short ribonucleotides known as micro-RNAs are found to be effective against CSCs. Micro-RNAs function as negative regulators of certain genes that potentiates the tumorigenesis and metastasis of CSCs.

Therapeutic efficacy of microRNAs depends on overcoming the extracellular (protein degradation of genetic materials) and intracellular (escape from late endosomes/lysosomes to avoid enzymatic degradation) barriers.

A team of researchers from the Ohio State University has developed a nanobomb technology to overcome these barriers, thereby achieving effective killing of CSCs. Micro-RNAs are encapsulated along with ammonium bicarbonate and ICG molecule inside a PLGA-Lipid-Polymer shell and are delivered to the target CSCs.

After the uptake of the nanoparticles, the cells are irradiated with NIR laser. ICG a photosensitizer molecule absorbs the light and generates heat resulting in the gas formation due to the presence of ammonium bicarbonate. The CO2 generated expands the nanoparticles to 300 nm which is almost 3 times its original size (~100nm), sufficient enough to break open the endosomes/lysosomes (150-200 nm), thus releasing the micro-RNAs in the cytoplasm. Micro-RNA-34a (miR-34a) effective against CD44 gene overexpressed in prostrate CSCs, was used in this study. The miR-34a nanobombs was highly specific to prostrate CSCs and significantly reduced the tumour volume as well the CD44 expression in tumour bearing mice models.

This study has been published in the journal Advanced Materials.

 

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