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Addressing this, proteolysis\u2010targeting chimeras (PROTACs) have become a cutting\u2010edge treatment method, emphasizing protein degradation. A modified ethanol injection method was employed in this study to formulate liposomes encapsulating PROTAC drug LC\u20102 (LC\u20102 LPs). Precise surface modifications using cell\u2010penetrating peptide R8 yielded R8\u2010LC\u20102 liposomes (R8\u2010LC\u20102 LPs). Comprehensive cellular uptake and cytotoxicity studies unveiled that R8\u2010LC\u20102 LPs depended on concentration and time, showcasing the superior performance of R8\u2010LC\u20102 LPs compared to normal liposomes. In vivo pharmacokinetic profiles demonstrated the capacity of DSPE\u2010PEG2000 to prolong the circulation time of LC\u20102, leading to higher plasma concentrations compared to free LC\u20102. In vivo antitumor efficacy research underscored the remarkable ability of R8\u2010LC\u20102 LPs to effectively suppress tumor growth. This study contributed to the exploration of enhanced therapeutic strategies for NSCLC, specifically focusing on the development of liposomal PROTACs targeting the \u201cundruggable\u201d KRAS protein. The findings provide valuable insights into the potential of this innovative approach, offering prospects for improved drug delivery and heightened antitumor efficacy.<\/jats:p>","DOI":"10.1002\/ddr.22241","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T02:15:36Z","timestamp":1722910536000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Targeted degradation of KRAS protein in non\u2010small cell lung cancer: Therapeutic strategies using liposomal PROTACs with enhanced cellular uptake and pharmacokinetic profiles"],"prefix":"10.1002","volume":"85","author":[{"given":"Xiaowen","family":"Wang","sequence":"first","affiliation":[{"name":"Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs, School of Pharmacy Yantai University Yantai Shandong 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