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Cell\u2010penetrating peptides (CPPs) offer a promising strategy to enhance intracellular drug delivery. In this study, we designed a novel tumor\u2010penetrating peptide, P3 (sequence: Trp\u2010Lys\u2010Ala\u2010Ser\u2010Cys), which demonstrated exceptional transmembrane efficiency with a broad\u2010spectrum penetration profile across various tumor cell lines (including HeLa, HGC\u201027, and A549 etc.). Notably, it achieved an internalization rate of 47.4% in A549 cells within 15 min. This peptide was further engineered into an amphiphilic polymer, P3\u2010Mal\u2010PEG\u2010PCL, which self\u2010assembled into pH\u2010responsive micelles. Doxorubicin (DOX) was encapsulated within these micelles to form DOX@P3P, which was subsequently coated with hyaluronic acid (HA) to create the final actively targeted nanoparticles, DOX@P3P@HA (PHA NPs), leveraging the cluster of differentiation 44 (CD44) receptor overexpression on cancer cells. The PHA NPs displayed excellent biosafety, colloidal stability, and improved drug distribution. In a murine tumor model, treatment with PHA NPs resulted in a remarkable 76.6% reduction in tumor volume, underscoring its potent antitumor efficacy and highlighting its potential as a robust platform for targeted cancer chemotherapy.<\/jats:p>","DOI":"10.1002\/smll.75785","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:21:48Z","timestamp":1789568508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Broad\u2010Spectrum Tumor\u2010Penetrating Peptide WKASC: Design, Screening, and Platform Development for Cancer Therapy"],"prefix":"10.1002","author":[{"given":"Yichen","family":"Tian","sequence":"first","affiliation":[{"name":"College of Chemistry and Chemical Engineering College of Materials Science and Engineering Institute of Biomedical Materials and Engineering Qingdao University  Qingdao 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