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Pharmacophore hybridization and nanoscale assembly to discover new self-delivering lysosomotropic chemical entities for cancer therapy

ABSTRACT: Pharmacophore hybridization and nanoscale assembly to discover new self-delivering lysosomotropic chemical entities for cancer therapy

PROVIDER: PRJNA645892 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12211182.fastq.gz	Fastqsanger.gz
	SRR12211183.fastq.gz	Fastqsanger.gz
	SRR12211184.fastq.gz	Fastqsanger.gz
	SRR12211185.fastq.gz	Fastqsanger.gz
	SRR12211186.fastq.gz	Fastqsanger.gz

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Pharmacophore hybridization and nanoscale assembly to discover new self-delivering lysosomotropic chemical entities for cancer therapy

Project description:Cancer lysosome is a potential target for cancer therapy. We designed and prepared a type of single-drug nanoparticles. These nanoparticles can specifically accumulate in lysosomes when entering cancer cells and are dissociated into small molecules. The small molecules not only act as lysosomotropic detergents to induce lysosomal membrane permeabilization directly, but also act as lysosomomotropic alkalizers to inhibit autophagy. In the meanwhile, these nanoparticles also show a strong proton-sponging effect and induce lysosomal dysfunction. As a result, the nanoparticles exhibit good antiproliferative activity in vitro. These single-drug nanoparticles also demonstrate excellent pharmacokinetic and toxicological profiles and dramatic antitumour efficacy in vivo. In addition, they are able to encapsulate and deliver additional drugs to tumour sites and are thus promising agents for autophagy inhibition-based combination therapy. Given their transdisciplinary advantages, these nanoparticles have enormous potential to improve cancer therapy.

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