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Large-scale Screening Reveals Genomic Factors That Determine Nanoparticles Delivery Efficiency
EP39127
Poster Title: Large-scale Screening Reveals Genomic Factors That Determine Nanoparticles Delivery Efficiency
Submitted on 09 Aug 2022
Author(s): Sonia Li
Affiliations: Biopharma PEG Scientific Inc.
Poster Views: 132
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Poster Information
Abstract: The approval and mass vaccination of two COVID-19 mRNA vaccines have made everyone aware of the great potential of lipid nanoparticles (LNPs) as delivery vehicles. In addition to being used to deliver vaccines, nanoparticle (NP)-based therapies also hold great potential for personalized cancer treatment, with nanoparticles being able to encapsulate a range of goods, including small molecules, biological agents, nucleic acids and more. Thus, nanoparticles loaded with therapeutic drugs can be designed to prevent accidental degradation of therapeutic drugs during delivery, to increase their circulation time in the body, and to specifically deliver drugs to specific tissues such as tumors.

Although using nanoparticles as carriers to deliver anticancer drugs is a potential way to treat cancer and avoid the side effects of chemotherapy, only a few nanoparticle-based anticancer drugs have been approved by the FDA so far.

A major challenge for successful targeted delivery of nanoparticles is that the nanobiological interactions at the target site are not well understood, and the diversity of cancer types and targets means that a full understanding of which nanoparticle properties determine successful delivery and targeting is a formidable challenge.

cancer cells

On July 22, 2022, researchers from the Massachusetts Institute of Technology (MIT) and the Broad Institute published a research paper titled: Massively parallel pooled screening reveals genomic determinants of nanoparticle delivery in the journal Science.

The study analyzed the interactions between 35 different types of nanoparticles and nearly 500 types of cancer cells, revealing thousands of biological features that influence the uptake of different types of nanoparticles by these cancer cells. This study identified the SLC46A3 protein as a negative regulator and potential biomarker of cellular uptake of lipid-based nanoparticles.

These findings help to better tailor drug delivery nanoparticle carriers to specific cancer types, or to customize novel nanoparticle carriers using the cellular biology of specific cancers, to overcome current barriers to the development of nanoparticle-based drugs.

Paula Hammond, the paper's corresponding author and professor at MIT and chair of the Department of Chemical Engineering, said she is excited about the findings, which can be used to determine which types of nanoparticles are suitable for targeting certain cell types, from cancer cells to immune cells and other types of cells of the healthy or diseased organs, and this is only a start.

The Paula Hammond lab has previously developed several types of nanoparticles that can be used to deliver drugs into cells. In further research, they found that different types of cancer cells often showed different responses to the same nanoparticle particles. They believe that biological differences between cells may be responsible for this different response.

To figure out the real reasons behind these different responses, the research team conducted a large-scale study to observe the interactions between a large number of different cells and many different types of nanoparticles.

The research team used the Broad Institute's PRISM platform, which rapidly screens thousands of drugs in hundreds of different cancer cell types simultaneously. The team adapted the PRISM platform from cell-drug interactions to screening cell-nanoparticle interactions to assess whether the genotypic characteristics of cells can predict the uptake of nanoparticles by cells.

The research team used 488 cancer cell lines from 22 different tissues. Each cancer cell type carries a unique "barcode" of DNA sequences so that these cells can be identified in subsequent screening. For each cancer cell type, extensive datasets on its gene expression profile and other biological characteristics are also available.
Summary: Large-scale screening reveals genomic factors that determine nanoparticles delivery efficiency, this is a breakthrough in cancer nanomedicine.References: [1] How different cancer cells respond to drug-delivering nanoparticles.
[2] One step closer to cancer nanomedicine.
[3] Massively parallel pooled screening reveals genomic determinants of nanoparticle delivery.
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