{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:16:32Z","timestamp":1788254192861,"version":"build-2803163510"},"reference-count":161,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Basic Research Project of Yunnan Province","award":["202501AT070335"],"award-info":[{"award-number":["202501AT070335"]}]},{"name":"TCM Joint Project of Yunnan Province","award":["202301AZ070001-033"],"award-info":[{"award-number":["202301AZ070001-033"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460988"],"award-info":[{"award-number":["82460988"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32160223"],"award-info":[{"award-number":["32160223"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82460988"],"award-info":[{"award-number":["82460988"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["32160223"],"award-info":[{"award-number":["32160223"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Paclitaxel (PTX) remains a major component of treatment for solid tumors, but its clinical performance is limited by poor aqueous solubility, solvent-associated toxicity, heterogeneous tumor exposure, and multifactorial drug resistance. This narrative review examines PTX nanomedicines from a molecular pharmacology perspective, focusing on how carrier design interacts with resistance pathways, tumor microenvironment signals, and intracellular drug trafficking. We outline resistance mechanisms involving ATP-binding cassette subfamily B member 1 (ABCB1)\/P-glycoprotein (P-gp)-mediated efflux, microtubule remodeling, apoptosis-related signaling, epigenetic regulation, extracellular matrix deposition, hypoxia, and redox imbalance. We evaluate albumin-bound formulations, liposomes, polymeric micelles, stimuli-responsive carriers, biomimetic systems, carrier-free prodrug assemblies, and multidrug co-delivery platforms according to the molecular and biological barriers they address. Particular attention is given to pH-, redox-, enzyme-, and hypoxia-responsive release; tissue penetration and subcellular localization; and co-delivery of PTX with chemosensitizers, nucleic acids, or pathway-directed agents. Molecular simulation and machine learning are considered as tools for formulation optimization and biomarker-guided patient stratification. These approaches can coordinate drug exposure and resistance modulation in preclinical models, but clinical benefits remain inconsistent. Translation will require reproducible formulations, clinically predictive models, direct measurement of intratumoral drug levels, and validated biomarkers linking molecular delivery mechanisms to patient outcomes.<\/jats:p>","DOI":"10.3390\/ijms27177690","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:47:13Z","timestamp":1787849233000},"page":"7690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Paclitaxel Nanomedicines: Molecular Mechanisms of Drug Resistance, Tumor Microenvironment-Responsive Delivery, and Translational Challenges"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9432-4844","authenticated-orcid":false,"given":"Dejun","family":"Cheng","sequence":"first","affiliation":[{"name":"Institute of Information, Yunnan University of Chinese Medicine, Kunming 650500, China"},{"name":"Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Gastrointestinal Diseases, Yunnan Provincial Department of Education, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7886-1453","authenticated-orcid":false,"given":"Guowei","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Information, Yunnan University of Chinese Medicine, Kunming 650500, China"},{"name":"Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Gastrointestinal Diseases, Yunnan Provincial Department of Education, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1869-1206","authenticated-orcid":false,"given":"Ruibin","family":"Kong","sequence":"additional","affiliation":[{"name":"Institute of Information, Yunnan University of Chinese Medicine, Kunming 650500, China"},{"name":"Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Gastrointestinal Diseases, Yunnan Provincial Department of Education, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Nursing, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Gastrointestinal Diseases, Yunnan Provincial Department of Education, Kunming 650500, China"},{"name":"Yunnan Engineering Research Centre of Preventive Treatment of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunpeng","family":"Luan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Gastrointestinal Diseases, Yunnan Provincial Department of Education, Kunming 650500, China"},{"name":"Yunnan Engineering Research Centre of Preventive Treatment of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2038-5406","authenticated-orcid":false,"given":"Qijiang","family":"Shu","sequence":"additional","affiliation":[{"name":"Institute of Information, Yunnan University of Chinese Medicine, Kunming 650500, China"},{"name":"Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Gastrointestinal Diseases, Yunnan Provincial Department of Education, Kunming 650500, China"},{"name":"Yunnan Engineering Research Centre of Preventive Treatment of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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