{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:52:11Z","timestamp":1792068731298,"version":"4.4.0"},"reference-count":33,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Over the past 5\u2009years, the number of antibody\u2013drug conjugates (ADCs) entering the oncology market has surged. By contrast, the clinical use of immunoliposomes\u2014nanoparticles that also employ antibodies as targeting agents (i.e., antibody\u2013nanoconjugates, ANCs)\u2014has yet to receive approval. One possible reason is the limited understanding of the relationship between ANC exposure and efficacy. To address this gap, we developed a pharmacokinetic\/pharmacodynamic (PK\/PD) model for a docetaxel\u2013trastuzumab ANC. PK and PD studies were conducted in MDA\u2010MB\u2010231 tumor\u2013bearing mice, divided into three treatment groups: (i)\u00a0control, (ii) free docetaxel + free trastuzumab, and (iii) docetaxel\u2013trastuzumab ANCs. PK data were obtained by fluorescence imaging and captured systemic and tumor distribution of ANCs, while PD data were based on tumor growth measurements. The PK model was built using data from the ANC group, and the PD model was developed across all three treatment groups, with a leave\u2010one\u2010out cross validation strategy for predictive evaluation. Treatment schedule simulations were then performed. Using a population nonlinear mixed\u2010effects (NLME) approach, the final PK model included a central and a tumor compartment, each with independent elimination rates. Tumor growth dynamics were best described by a reduced Gompertz model coupled with a Simeoni resistance model. This model demonstrated strong predictive performance. Using only data from the first two treatment cycles (4 time points) and Bayesian estimation in the test set, it accurately predicted systemic and tumor ANC concentrations across the subsequent four treatment cycles, with a relative error (RE) below 15%. Prediction precision was further improved (RE\u2009&lt;\u20095%) when data from one additional treatment cycle were incorporated. Similar performance was achieved for PD data, with tumor volume predictions exhibiting RE\u2009&lt;\u200915% and RE\u2009&lt;\u20097.5% when implementing data from two and three treatment cycles, respectively. The model was then applied to simulate alternative treatment schedules. Interestingly, while systemic exposure remained comparable across regimens, every\u20105\u2010day administration yielded the greatest tumor exposure compared to daily, weekly, and every\u201035\u2010day dosing (mean\u2009\u00b1\u2009SD tumor AUC: 55.4\u2009\u00b1\u200910.9\u2009mg\/kg day vs. 47.6\u2009\u00b1\u20099.38\u2009mg\/kg day, 51.4\u2009\u00b1\u200911.5\u2009mg\/kg day, and 44.6\u2009\u00b1\u200910.0\u2009mg\/kg day, respectively, one\u2010way ANOVA,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), highlighting the importance of dosing frequency. Overall, these results illustrate how PK\/PD modeling can refine intra\u2010tumor PK understanding and support preclinical development of innovative formulations such as ANCs.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70348","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T08:40:20Z","timestamp":1791794420000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical Pharmacokinetic\u2010Pharmacodynamic Modeling of Antibody Nanoconjugates for Breast Cancer Treatment"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0787-8241","authenticated-orcid":false,"given":"Anne","family":"Rodallec","sequence":"first","affiliation":[{"name":"COMPutational Pharmacology and Clinical Oncology Centre Inria D'universit\u00e9 C\u00f4te D'azur, Aix Marseille Univ, CNRS, INSERM, Institut Paoli\u2010Calmettes, CRCM  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Vaghi","sequence":"additional","affiliation":[{"name":"MONC, Mod\u00e9lisation Math\u00e9matique Pour L'oncologie Centre Inria de L'universit\u00e9 de Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Ciccolini","sequence":"additional","affiliation":[{"name":"COMPutational Pharmacology and Clinical Oncology Centre Inria D'universit\u00e9 C\u00f4te D'azur, Aix Marseille Univ, CNRS, INSERM, Institut Paoli\u2010Calmettes, CRCM  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphaelle","family":"Fanciullino","sequence":"additional","affiliation":[{"name":"COMPutational Pharmacology and Clinical Oncology Centre Inria D'universit\u00e9 C\u00f4te D'azur, Aix Marseille Univ, CNRS, INSERM, Institut Paoli\u2010Calmettes, CRCM  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3749-8637","authenticated-orcid":false,"given":"Sebastien","family":"Benzekry","sequence":"additional","affiliation":[{"name":"COMPutational Pharmacology and Clinical Oncology Centre Inria D'universit\u00e9 C\u00f4te D'azur, Aix Marseille Univ, CNRS, INSERM, Institut Paoli\u2010Calmettes, CRCM  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03502-3"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-02108-4"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2203690"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12645-025-00314-5"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S162454"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S179290"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2018.06.008"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10544-019-0380-2"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.114138"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn500299p"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2012.05.046"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0905487106"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn1018818"},{"key":"e_1_2_9_15_1","first-page":"3365","article-title":"A Physiologically Based Pharmacokinetic Model for Ionic Silver and Silver Nanoparticles","volume":"8","author":"Bachler G.","year":"2013","journal-title":"International Journal of Nanomedicine"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2020.02.014"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-017-0071-y"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12892"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-2524"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1007178"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.21.0807"},{"key":"e_1_2_9_22_1","first-page":"1037","article-title":"Phase I and Pharmacokinetic Study of Taxotere (RP 56976; NSC 628503) Given as a Short Intravenous Infusion","volume":"53","author":"Extra J. 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