2023 article
Microneedle Patch Delivery of PROTACs for Anti-Cancer Therapy
Cheng, X., Hu, S., & Cheng, K. (2023, June 9). ACS NANO.
author keywords: PROTAC; estrogen receptor; microneedle patch; hyaluronic acid gel; ER-positive breast cancer
MeSH headings : Humans; Female; Estrogen Receptor alpha / metabolism; Proteolysis Targeting Chimera; Breast Neoplasms / pathology; Drug Delivery Systems / methods; Proteolysis
TL;DR:
The work demonstrates the feasibility and proof-of-concept therapeutic potential of using microneedle patches to directly deliver PROTACs into tumors and can sufficiently degrade ERα in MCF7 cells.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: June 26, 2023
Proteolysis-targeting chimera (PROTAC) is an emerging technique for degrading disease-related proteins. However, the current PROTACs suffer from inadequate solubility and lack of organ targeting, which has hampered their druggability. Herein, we report direct and sustained delivery of PROTACs using microneedle patches to the diseased tissues. In this study, we use an estrogen receptor alpha (ERα)-degrading PROTAC, ERD308, to treat ER-positive breast cancer. A pH-sensitive micelle, MPEG-poly(β-amino ester) (MPEG-PAE), is used to encapsulate ERD308 along with an FDA-approved CDK4/6 inhibitor, Palbociclib (Pal), before loading into biodegradable microneedle patches. These patches enable prolonged drug release into deep tumors, maintaining therapeutic levels for at least 4 days, with an excellent drug retention rate of over 87% in tumors. ERD308 released from the microneedle patches can sufficiently degrade ERα in MCF7 cells. Co-administration of ERD308 and Palbociclib exhibits excellent efficacy by over 80% tumor reduction as well as a good safety profile. Our work demonstrates the feasibility and proof-of-concept therapeutic potential of using microneedle patches to directly deliver PROTACs into tumors.
