Dataset Information

A novel enzyme-mediated method for covalent surface modification of extracellular vesicles to achieve targeted drug delivery

ABSTRACT: Natural extracellular vesicles (EVs) are ideal drug carriers due to their remarkable biocompatibility. Their delivery specificity can be achieved by the conjugation of targeting ligands. However, existing methods to engineer target-specific EVs are tedious or inefficient, having to compromise between harsh chemical treatments or transient interactions. Here, we describe a novel method for the covalent conjugation of EVs with high copy numbers of targeting moieties using protein ligases. Conjugation of EVs with either an epidermal growth factor receptor (EGFR)-targeting peptide or anti-EGFR nanobody facilitates their accumulation in EGFR-positive cancer cells, both in vitro and in vivo. Systemic delivery of paclitaxel by EGFR-targeting EVs at a low dose significantly increases drug efficacy in a xenografted mouse model of EGFR-positive lung cancer. The method is also applicable to the conjugation of EVs with peptides and nanobodies targeting other receptors, such as HER2 and SIRP alpha, and the conjugated EVs can deliver RNA in addition to small molecules, supporting the versatile application of EVs in cancer therapies. This simple, yet efficient and versatile method for the stable surface modification of EVs bypasses the need for genetic and chemical modifications, thus facilitating safe and specific delivery of therapeutic payloads to target cells.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood

SUBMITTER: Dennis Kappei

LAB HEAD: Dennis Kappei

PROVIDER: PXD021926 | Pride | 2021-03-24

REPOSITORIES: Pride

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			Action	DRS
	20200913_QPC_DK_SoM_ML_JM_EVs_biotin_peptide_01.raw	Raw
	20200913_QPC_DK_SoM_ML_JM_EVs_biotin_peptide_02.raw	Raw
	20200913_QPC_DK_SoM_ML_JM_EVs_biotin_peptide_03.raw	Raw
	20200913_QPC_DK_SoM_ML_JM_EVs_biotin_peptide_04.raw	Raw
	20200913_QPC_DK_SoM_ML_JM_EVs_biotin_peptide_pulldown.zip	Other

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Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery.

Pham Tin Chanh TC Jayasinghe Migara Kavishka MK Pham Thach Tuan TT Yang Yuqi Y Wei Likun L Usman Waqas Muhammad WM Chen Huan H Pirisinu Marco M Gong Jinhua J Kim Seongkyeol S Peng Boya B Wang Weixi W Chan Charlene C Ma Victor V Nguyen Nhung T H NTH Kappei Dennis D Nguyen Xuan-Hung XH Cho William C WC Shi Jiahai J Le Minh T N MTN

Journal of extracellular vesicles 20210216 4

Natural extracellular vesicles (EVs) are ideal drug carriers due to their remarkable biocompatibility. Their delivery specificity can be achieved by the conjugation of targeting ligands. However, existing methods to engineer target-specific EVs are tedious or inefficient, having to compromise between harsh chemical treatments and transient interactions. Here, we describe a novel method for the covalent conjugation of EVs with high copy numbers of targeting moieties using protein ligases. Conjuga ...[more]

PMID: 33643546

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