{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T07:36:37Z","timestamp":1774251397832,"version":"3.50.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Paclitaxel (PTX) remains a widely used chemotherapeutic agent for treating diverse solid tumors, but its clinical utility is constrained by pronounced hydrophobicity, which necessitates the use of formulation surfactants and contributes to a narrow therapeutic window. To overcome these limitations, we developed a TROP2-targeted antibody-drug conjugate (ADC) designed for selective and solvent-free delivery of PTX.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The ADC, designated hRS7-PTX, was generated by conjugating PTX to the humanized anti-TROP2 monoclonal antibody (hRS7) through a rationally engineered, PEGylated, protease-cleavable linker. The conjugate was characterized for its physicochemical stability, solubility, and antigen-dependent cytotoxic activity\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                      <jats:italic>In vivo<\/jats:italic>\n                      efficacy and biodistribution were evaluated in murine xenograft models of TROP2-expressing tumors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      hRS7-PTX demonstrated high aqueous stability and maintained favorable physicochemical properties without the need for organic co-solvents.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , the ADC induced potent, antigen-dependent cytotoxicity, preferentially killing TROP2-positive tumor cells while sparing antigen-negative cells. In murine xenograft models, hRS7-PTX treatment produced sustained tumor regression and significantly outperformed weight-equivalent doses of conventional PTX formulations. Fluorescence imaging further confirmed rapid and preferential accumulation of hRS7-PTX within TROP2-rich tumor tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings establish hRS7-PTX as an effective, solvent-free strategy for targeted PTX delivery that expands the therapeutic index of this widely used drug. The combination of selective tumor targeting, improved tolerability, and robust antitumor activity supports the further development of hRS7-PTX for the treatment of TROP2-positive malignancies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1805542","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T06:42:43Z","timestamp":1774248163000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Antibody conjugation of paclitaxel enables aqueous compatibility and enhances tumor-targeted efficacy in vitro and in vivo"],"prefix":"10.3389","volume":"17","author":[{"given":"Gul E.","family":"Rana","sequence":"first","affiliation":[{"name":"Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]},{"name":"University of Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shufan","family":"Yang","sequence":"additional","affiliation":[{"name":"Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]},{"name":"University of Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanting","family":"He","sequence":"additional","affiliation":[{"name":"Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengcheng","family":"Qiu","sequence":"additional","affiliation":[{"name":"Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]},{"name":"University of Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Long","sequence":"additional","affiliation":[{"name":"Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yezhen","family":"Huang","sequence":"additional","affiliation":[{"name":"Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]},{"name":"University of Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]},{"name":"Joint National Laboratory for Antibody Drug Engineering, School of Medicine, Henan University","place":["Kaifeng, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jincheng","family":"Luo","sequence":"additional","affiliation":[{"name":"Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]},{"name":"Wuya College of Innovation, Shenyang Pharmaceutical University","place":["Shenyang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jindi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]},{"name":"School of Life Science and Technology, China Pharmaceutical University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siwen","family":"Xu","sequence":"additional","affiliation":[{"name":"Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]},{"name":"New College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-He","family":"Wang","sequence":"additional","affiliation":[{"name":"Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]},{"name":"University of Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"362","DOI":"10.4161\/mabs.19449","article-title":"Impact of linker and conjugation chemistry on antigen binding, Fc receptor binding and thermal stability of model antibody-drug conjugates","volume":"4","author":"Acchione","year":"2012","journal-title":"MAbs"},{"key":"B2","doi-asserted-by":"publisher","first-page":"102552","DOI":"10.1016\/j.nantod.2024.102552","article-title":"Breaking biological barriers: engineering polymeric nanoparticles for cancer therapy","volume":"60","author":"Austria","year":"2025","journal-title":"Nano Today"},{"key":"B3","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.xphs.2019.08.006","article-title":"Alteration of physicochemical properties for antibody-drug conjugates and their impact on stability","volume":"109","author":"Buecheler","year":"2020","journal-title":"J. Pharm. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/s12943-023-01865-0","article-title":"Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation","volume":"22","author":"Chehelgerdi","year":"2023","journal-title":"Mol. Cancer"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1080\/10717544.2020.1797245","article-title":"Adjudin-loaded redox-sensitive paclitaxel-prodrug micelles for overcoming multidrug resistance with efficient targeted Colon cancer therapy","volume":"27","author":"Chen","year":"2020","journal-title":"Drug Deliv."},{"key":"B6","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1186\/s12943-025-02489-2","article-title":"Antibody-drug conjugates in cancer therapy: current landscape, challenges, and future directions","volume":"24","author":"Chen","year":"2025","journal-title":"Mol. Cancer"},{"key":"B7","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/s41571-021-00470-8","article-title":"Unlocking the potential of antibody\u2013drug conjugates for cancer therapy","volume":"18","author":"Drago","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2621","DOI":"10.1016\/j.xphs.2023.08.002","article-title":"Studying intermolecular interactions in an antibody-drug conjugate through chemical screening and computational modeling","volume":"112","author":"Ebrahimi","year":"2023","journal-title":"J. Pharm. Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.jncc.2025.01.007","article-title":"Advancements in antibody-drug conjugates as cancer therapeutics","volume":"5","author":"Fong","year":"2025","journal-title":"J. Natl. Cancer Cent."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1007\/s00520-009-0588-4","article-title":"Retrospective evaluation of weekly paclitaxel hypersensitivity reactions reported utilizing an electronic medical record system at a tertiary cancer center","volume":"17","author":"Lal","year":"2009","journal-title":"Support Care Cancer"},{"key":"B11","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/s41598-019-57380-0","article-title":"Efficacy and safety of nanoparticle-albumin-bound paclitaxel compared with solvent-based taxanes for metastatic breast cancer: a meta-analysis","volume":"10","author":"Lee","year":"2020","journal-title":"Sci. Rep."},{"key":"B12","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1097\/CAD.0000000000000173","article-title":"Cytotoxic and antiangiogenic paclitaxel solubilized and permeation-enhanced by natural product nanoparticles","volume":"26","author":"Liu","year":"2015","journal-title":"Anticancer Drugs"},{"key":"B13","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1021\/acs.bioconjchem.4c00392","article-title":"PEGylation of dipeptide linker improves therapeutic index and pharmacokinetics of antibody-drug conjugates","volume":"36","author":"Long","year":"2025","journal-title":"Bioconjug Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1208\/s12248-014-9710-8","article-title":"Antibody-drug conjugates: design and selection of linker, payload and conjugation chemistry","volume":"17","author":"McCombs","year":"2015","journal-title":"AAPS J."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2904","DOI":"10.3390\/cancers14122904","article-title":"Nanomedicine penetration to tumor: challenges, and advanced strategies to tackle this issue","volume":"14","author":"Munir","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B16","doi-asserted-by":"publisher","first-page":"500","DOI":"10.3390\/biomedicines9050500","article-title":"Paclitaxel-based chemotherapy targeting cancer stem cells from mono-to combination therapy","volume":"9","author":"Nawara","year":"2021","journal-title":"Biomedicines"},{"key":"B17","doi-asserted-by":"publisher","first-page":"713","DOI":"10.3390\/cancers15030713","article-title":"Mechanisms of ADC toxicity and strategies to increase ADC tolerability","volume":"15","author":"Nguyen","year":"2023","journal-title":"Cancers"},{"key":"B18","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1158\/1078-0432.CCR-22-3640","article-title":"New life of topoisomerase I inhibitors as antibody-drug conjugate warheads","volume":"29","author":"Pommier","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/s41392-020-00247-y","article-title":"Construction of paclitaxel-based antibody\u2013drug conjugates with a PEGylated linker to achieve superior therapeutic index","volume":"5","author":"Shao","year":"2020","journal-title":"Signal Transduct. Target Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.1039\/d5nr04462f","article-title":"Factors governing tumor penetration of nanomedicines: intrinsic and extrinsic determinants","volume":"18","author":"Shin","year":"2026","journal-title":"Nanoscale"},{"key":"B21","doi-asserted-by":"publisher","first-page":"3541","DOI":"10.1007\/s11095-015-1704-4","article-title":"Antibody-drug conjugates: design, formulation and physicochemical stability","volume":"32","author":"Singh","year":"2015","journal-title":"Pharm. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"193","DOI":"10.3390\/pharmaceutics10040193","article-title":"Functional nanoparticles for tumor penetration of therapeutics","volume":"10","author":"Su","year":"2018","journal-title":"Pharmaceutics"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.3390\/ph17101338","article-title":"Present scenario and future landscape of payloads for ADCs: focus on DNA-interacting agents","volume":"17","author":"Valsasina","year":"2024","journal-title":"Pharm. (Basel)"},{"key":"B24","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1080\/17425247.2022.2039621","article-title":"The development of peptide\u2013drug conjugate strategies for paclitaxel","volume":"19","author":"Wang","year":"2022","journal-title":"Expert Opin. Drug Deliv."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2619","DOI":"10.1002\/1097-0142(20000601)88:11<2619::aid-cncr26>3.0.co;2-j","article-title":"Paclitaxel-induced cell death: where the cell cycle and apoptosis come together","volume":"88","author":"Wang","year":"2000","journal-title":"Cancer"},{"key":"B26","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.jconrel.2017.09.026","article-title":"Preclinical development of drug delivery systems for paclitaxel-based cancer chemotherapy","volume":"267","author":"Wang","year":"2017","journal-title":"J. Control Release"},{"key":"B27","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s13045-025-01704-3","article-title":"Antibody-drug conjugates (ADCs): current and future biopharmaceuticals","volume":"18","author":"Wang","year":"2025","journal-title":"J. Hematol. Oncol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.3390\/cancers17111792","article-title":"Advancing antibody\u2013drug conjugates: precision oncology approaches for breast and pancreatic cancers","volume":"17","author":"Yajaman","year":"2025","journal-title":"Cancers"},{"key":"B29","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1080\/10717540601098799","article-title":"Liposome formulation of paclitaxel with enhanced solubility and stability","volume":"14","author":"Yang","year":"2007","journal-title":"Drug Deliv."},{"key":"B30","doi-asserted-by":"publisher","first-page":"4337","DOI":"10.3390\/molecules20034337","article-title":"Bioavailability enhancement of paclitaxel via a novel oral drug delivery system: paclitaxel-loaded glycyrrhizic acid micelles","volume":"20","author":"Yang","year":"2015","journal-title":"Molecules"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1805542\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T06:42:43Z","timestamp":1774248163000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1805542\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,23]]},"references-count":30,"alternative-id":["10.3389\/fphar.2026.1805542"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1805542","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,23]]},"article-number":"1805542"}}