{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:03:10Z","timestamp":1785250990825,"version":"3.55.0"},"reference-count":73,"publisher":"American Chemical Society (ACS)","issue":"29","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"publisher","award":["N42A650185"],"award-info":[{"award-number":["N42A650185"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","award":["N42A650185"],"award-info":[{"award-number":["N42A650185"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lung cancer is the leading cause of cancer-related deaths worldwide, with growing evidence suggesting that exposure to fine particulate matter (PM2.5) contributes to cancer. However, conventional chemotherapeutics have limitations due to nonspecific biodistribution, systemic toxicity, and challenges in codelivering multiple drugs with different physicochemical properties. Here, we engineered yolk\u2013shell nanoparticles (YSNs) to achieve codelivery of doxorubicin (DOX, hydrophilic) and paclitaxel (PTX, hydrophobic). Rhodamine B (RhB, hydrophilic) and methylene blue (MB, hydrophobic) were also used as model drugs because they have drug release kinetics similar to those of DOX and PTX, respectively. We observed rapid and sustained release of RhB over 14 days and burst release of MB within 24 h. MB or PTX was released from the mesoporous organosilica shell, whereas biphasic RhB or DOX was released from the organosilica surface and silica inner core. Confocal microscopy confirmed the efficient cellular uptake and accumulation of YSNs around the nucleus. Blank YSNs were nontoxic to normal human bronchial epithelial cells (BEAS-2B) and lung cancer cells (A549). In A549 cells, YSNs coloaded with DOX\/PTX enhanced in vitro efficacy compared with free drugs, producing equivalent or greater cytotoxicity at reduced drug loadings, approximately 15-fold (DOX) and 10-fold (PTX) lower than the effective doses. These results highlight the potential of the YSN platform for dose\u2013efficient combination chemotherapy and its promising biocompatibility in a drug delivery system.<\/jats:p>","DOI":"10.1021\/acsomega.6c01657","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T04:35:08Z","timestamp":1783917308000},"page":"43364-43374","source":"Crossref","is-referenced-by-count":0,"title":["Engineered Yolk\u2013Shell\nNanocarriers for Biphasic\nRelease and Efficient Codelivery of Chemotherapy Drugs in Lung Cancer\nCells"],"prefix":"10.1021","volume":"11","author":[{"given":"Jiraporn","family":"Kamsarn","sequence":"first","affiliation":[{"name":"Chiang Mai University , , Mae Hia Campus , Mueang Chiang Mai District, ,","place":["Chiang Mai, Thailand, 50100"]},{"name":"Chiang Mai University , , Mae Hia Campus , Mueang Chiang Mai District, ,","place":["Chiang Mai, Thailand, 50100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ploydao","family":"Puangroglchana","sequence":"additional","affiliation":[{"name":"Chiang Mai University , , ,","place":["Chiang Mai, Thailand, 50200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarawut","family":"Kumphune","sequence":"additional","affiliation":[{"name":"Chiang Mai University , , Mae Hia Campus , Mueang Chiang Mai District, ,","place":["Chiang Mai, Thailand, 50100"]},{"name":"Chiang Mai University , , Mae Hia Campus , Mueang Chiang Mai District, ,","place":["Chiang Mai, Thailand, 50100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nipon","family":"Theera-Umpon","sequence":"additional","affiliation":[{"name":"Chiang Mai University , , Mae Hia Campus , Mueang Chiang Mai District, ,","place":["Chiang Mai, Thailand, 50100"]},{"name":"Chiang Mai University , , Mae Hia Campus , Mueang Chiang Mai District, ,","place":["Chiang Mai, Thailand, 50100"]},{"name":"Chiang Mai University , , ,","place":["Chiang Mai, Thailand, 50200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pathinan","family":"Paengnakorn","sequence":"additional","affiliation":[{"name":"Chiang Mai University , , Mae Hia Campus , Mueang Chiang Mai District, ,","place":["Chiang Mai, Thailand, 50100"]},{"name":"Chiang Mai University , , Mae Hia Campus , Mueang Chiang Mai District, ,","place":["Chiang Mai, Thailand, 50100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3125-7680","authenticated-orcid":true,"given":"Hansoo","family":"Park","sequence":"additional","affiliation":[{"name":"Chung-Ang University , , Korea, ,","place":["Seoul, Republic of Korea, 06974"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2549-410X","authenticated-orcid":true,"given":"Phornsawat","family":"Baipaywad","sequence":"additional","affiliation":[{"name":"Chiang Mai University , , Mae Hia Campus , Mueang Chiang Mai District, ,","place":["Chiang Mai, Thailand, 50100"]},{"name":"Chiang Mai University , , Mae Hia Campus , Mueang Chiang Mai District, ,","place":["Chiang Mai, Thailand, 50100"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"issue":"4","key":"2026072810084148300_cit1","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.jncc.2022.09.004","article-title":"Etiology\nof lung cancer: Evidence from epidemiologic studies","volume":"2","author":"Zou","year":"2022","journal-title":"J. Natl. Cancer Inst."},{"issue":"16","key":"2026072810084148300_cit2","doi-asserted-by":"publisher","first-page":"8661","DOI":"10.3390\/ijms22168661","article-title":"Current and Future Development in\nLung Cancer Diagnosis","volume":"22","author":"Nooreldeen","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2026072810084148300_cit3","doi-asserted-by":"publisher","first-page":"125606","DOI":"10.1016\/j.envpol.2024.125606","article-title":"Development of a dual PM2.5 sampling and direct exposure system incorporated\nan in vitro air\u2013liquid interface culture method: Application\nto the northern Thailand haze season","volume":"367","author":"Paengnakorn","year":"2025","journal-title":"Environ.\nPollut."},{"key":"2026072810084148300_cit4","doi-asserted-by":"publisher","first-page":"121467","DOI":"10.1016\/j.envres.2025.121467","article-title":"Effect modification of fine particulate matter (PM2.5)\nrelated hospital admissions by temperature in Thailand: A nationwide\ntime-series study","volume":"277","author":"Kliengchuay","year":"2025","journal-title":"Environ. Res."},{"key":"2026072810084148300_cit5","doi-asserted-by":"publisher","first-page":"5905","DOI":"10.3390\/molecules26195905","article-title":"Controlled Drug Delivery Systems:\nCurrent Status and\nFuture Directions","volume":"26","author":"Adepu","year":"2021","journal-title":"Molecules"},{"issue":"1","key":"2026072810084148300_cit6","doi-asserted-by":"publisher","first-page":"13249","DOI":"10.1038\/s41598-017-13320-4","article-title":"Dual-Drug Containing\nCore-Shell Nanoparticles for Lung Cancer Therapy","volume":"7","author":"Menon","year":"2017","journal-title":"Sci. Rep"},{"issue":"22","key":"2026072810084148300_cit7","doi-asserted-by":"publisher","first-page":"19614","DOI":"10.1021\/acsomega.9b02167","article-title":"Polymeric\nCore\u2013Shell Combinatorial Nanomedicine for Synergistic Anticancer\nTherapy","volume":"4","author":"Shanavas","year":"2019","journal-title":"ACS Omega"},{"key":"2026072810084148300_cit8","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.ejpb.2020.02.012","article-title":"Overcoming\nthe diverse\nmechanisms of multidrug resistance in lung cancer cells by photodynamic\ntherapy using pTHPP-loaded PLGA-lipid hybrid nanoparticles","volume":"149","author":"Pramual","year":"2020","journal-title":"Eur. J. Pharm. Biopharm."},{"issue":"4","key":"2026072810084148300_cit9","doi-asserted-by":"publisher","first-page":"883","DOI":"10.3390\/pharmaceutics14040883","article-title":"Nanocarrier\nDrug Delivery Systems: Characterization, Limitations, Future Perspectives\nand Implementation of Artificial Intelligence","volume":"14","author":"Alshawwa","year":"2022","journal-title":"Pharmaceutics"},{"issue":"18","key":"2026072810084148300_cit10","doi-asserted-by":"publisher","first-page":"6830","DOI":"10.1039\/D2NR00783E","article-title":"Egg-yolk\ncore\u2013shell mesoporous silica\nnanoparticles for high doxorubicin loading and delivery to prostate\ncancer cells","volume":"14","author":"Tiburcius","year":"2022","journal-title":"Nanoscale"},{"issue":"6","key":"2026072810084148300_cit11","doi-asserted-by":"publisher","first-page":"843","DOI":"10.3390\/polym16060843","article-title":"Polymer-Based Drug Delivery Systems for Cancer Therapeutics","volume":"16","author":"Ding","year":"2024","journal-title":"Polymers"},{"issue":"1","key":"2026072810084148300_cit12","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1038\/s41392-023-01642-x","article-title":"Smart nanoparticles\nfor cancer therapy","volume":"8","author":"Sun","year":"2023","journal-title":"Signal Transduction Targeted\nTher."},{"issue":"4","key":"2026072810084148300_cit13","doi-asserted-by":"publisher","first-page":"638","DOI":"10.3390\/nano9040638","article-title":"Lipid-Based\nNanoparticles: Application and Recent Advances in Cancer Treatment","volume":"9","author":"Garci\u0301a-Pinel","year":"2019","journal-title":"Nanomaterials"},{"issue":"9","key":"2026072810084148300_cit14","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.1002\/cplu.202000496","article-title":"Development\nof High-Drug-Loading Nanoparticles","volume":"85","author":"Liu","year":"2020","journal-title":"ChemPlusChem"},{"key":"2026072810084148300_cit15","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.biomaterials.2018.04.027","article-title":"Combinational\nstrategy for high-performance cancer chemotherapy","volume":"171","author":"Qin","year":"2018","journal-title":"Biomaterials"},{"issue":"21","key":"2026072810084148300_cit16","doi-asserted-by":"publisher","first-page":"5566","DOI":"10.1158\/0008-5472.can-12-1683","article-title":"Overcoming\nlimitations in nanoparticle drug\ndelivery: triggered, intravascular release to improve drug penetration\ninto tumors","volume":"72","author":"Manzoor","year":"2012","journal-title":"Cancer Res."},{"key":"2026072810084148300_cit17","doi-asserted-by":"publisher","first-page":"125285","DOI":"10.1016\/j.ijpharm.2025.125285","article-title":"Carrier-free\nnanoparticles for cancer theranostics with dual-mode magnetic resonance\nimaging\/fluorescence imaging and combination photothermal and chemodynamic\ntherapy","volume":"671","author":"Ding","year":"2025","journal-title":"Int. J. Pharm."},{"issue":"1","key":"2026072810084148300_cit18","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1080\/10717544.2017.1410256","article-title":"Co-delivery nanoparticles\nof anti-cancer drugs for improving chemotherapy efficacy","volume":"24","author":"Qi","year":"2017","journal-title":"Drug Deliv"},{"issue":"9","key":"2026072810084148300_cit19","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1021\/ar600032u","article-title":"Synthesis\nand functionalization of a mesoporous silica nanoparticle based on\nthe sol-gel process and applications in controlled release","volume":"40","author":"Trewyn","year":"2007","journal-title":"Acc. Chem. 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Funct. Mater."},{"issue":"2","key":"2026072810084148300_cit24","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1021\/acsabm.9b01111","article-title":"Fabrication of a pH\/Redox-Triggered\nMesoporous Silica-Based Nanoparticle with Microfluidics for Anticancer\nDrugs Doxorubicin and Paclitaxel Codelivery","volume":"3","author":"Yan","year":"2020","journal-title":"ACS Appl. Bio Mater."},{"issue":"12","key":"2026072810084148300_cit25","doi-asserted-by":"publisher","first-page":"3452","DOI":"10.1007\/s13346-024-01573-2","article-title":"Polyelectrolyte\ncomplexes based on a novel and sustainable hemicellulose-rich lignosulphonate\nfor drug delivery applications","volume":"14","author":"Dogaris","year":"2024","journal-title":"Drug Delivery\nTransl. Res."},{"key":"2026072810084148300_cit26","doi-asserted-by":"publisher","first-page":"589","DOI":"10.2147\/IJN.S338897","article-title":"ROS-Generating Amine-Functionalized Magnetic Nanoparticles\nCoupled with Carboxymethyl Chitosan for pH-Responsive Release of Doxorubicin","volume":"17","author":"Obireddy","year":"2022","journal-title":"Int. J. Nanomedicine"},{"issue":"6","key":"2026072810084148300_cit27","doi-asserted-by":"publisher","first-page":"694","DOI":"10.3390\/pharmaceutics17060694","article-title":"Kinetic and\nMethodological Insights\ninto Hydrophilic Drug Release from Mesoporous Silica Nanocarriers","volume":"17","author":"Rozas","year":"2025","journal-title":"Pharmaceutics"},{"issue":"4","key":"2026072810084148300_cit28","doi-asserted-by":"publisher","first-page":"42","DOI":"10.3390\/colloids8040042","article-title":"Co-Encapsulation of Paclitaxel and\nDoxorubicin in Liposomes Layer by Layer","volume":"8","author":"Mota Di\u0301az","year":"2024","journal-title":"Colloids\nInterfaces"},{"key":"2026072810084148300_cit29","doi-asserted-by":"publisher","first-page":"116060","DOI":"10.1016\/j.carbpol.2020.116060","article-title":"Engineering butylglyceryl-modified\npolysaccharides towards nanomedicines for brain drug delivery","volume":"236","author":"Bostanudin","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"2026072810084148300_cit30","doi-asserted-by":"publisher","first-page":"125395","DOI":"10.1016\/j.molliq.2024.125395","article-title":"Two alternative approaches for the\nmagnetic adsorption of the hydrophobic dye Methylene Blue","volume":"409","author":"Sannino","year":"2024","journal-title":"J. Mol. Liq."},{"key":"2026072810084148300_cit31","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.jiec.2017.04.023","article-title":"Size-controlled synthesis,\ncharacterization, and cytotoxicity study of monodisperse poly(dimethylsiloxane)\nnanoparticles","volume":"53","author":"Baipaywad","year":"2017","journal-title":"J. Ind. Eng. Chem."},{"issue":"12","key":"2026072810084148300_cit32","doi-asserted-by":"publisher","first-page":"13636","DOI":"10.1021\/acsomega.3c07548","article-title":"Itaconic Acid\nCross-Linked Biomolecule Immobilization\nApproach on Amine-Functionalized Silica Nanoparticles for Highly Sensitive\nEnzyme-Linked Immunosorbent Assay (ELISA)","volume":"9","author":"Udomsom","year":"2024","journal-title":"ACS\nOmega"},{"issue":"3","key":"2026072810084148300_cit33","doi-asserted-by":"publisher","first-page":"2220","DOI":"10.1021\/acsami.5b10942","article-title":"Functionalized Mesoporous Silica\nvia an Aminosilane Surfactant Ion Exchange Reaction: Controlled Scaffold\nDesign and Nitric Oxide Release","volume":"8","author":"Soto","year":"2016","journal-title":"ACS Appl. Mater.\nInterfaces"},{"issue":"3","key":"2026072810084148300_cit34","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3390\/pharmaceutics9030035","article-title":"Pharmacokinetic and Toxicodynamic Characterization\nof a Novel Doxorubicin Derivative","volume":"9","author":"Alrushaid","year":"2017","journal-title":"Pharmaceutics"},{"key":"2026072810084148300_cit35","doi-asserted-by":"publisher","first-page":"31","DOI":"10.7324\/japs.2021.120204","article-title":"Synergistic effect of Paclitaxel\nand Curcumin in nano-formulations on U87 and A549 cancer cell lines","volume":"12","author":"Joyceline","year":"2022","journal-title":"J. Appl. Pharmaceut. Sci."},{"key":"2026072810084148300_cit36","doi-asserted-by":"publisher","first-page":"999","DOI":"10.2147\/IJN.S28088","article-title":"Delivering hydrophilic and hydrophobic chemotherapeutics simultaneously\nby magnetic mesoporous silica nanoparticles to inhibit cancer cells","volume":"7","author":"Liu","year":"2012","journal-title":"Int. J. Nanomedicine"},{"issue":"5","key":"2026072810084148300_cit37","doi-asserted-by":"publisher","first-page":"054107","DOI":"10.1063\/1.4962992","article-title":"Physical\ncharacterization of nanoparticle size and surface modification using\nparticle scattering diffusometry","volume":"10","author":"Clayton","year":"2016","journal-title":"Biomicrofluidics"},{"issue":"2","key":"2026072810084148300_cit38","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3390\/pharmaceutics10020057","article-title":"Impact of Particle Size and Polydispersity Index on\nthe Clinical Applications of Lipidic Nanocarrier Systems","volume":"10","author":"Danaei","year":"2018","journal-title":"Pharmaceutics"},{"issue":"4","key":"2026072810084148300_cit39","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s12551-016-0218-6","article-title":"Dynamic\nlight scattering: a practical\nguide and applications in biomedical sciences","volume":"8","author":"Stetefeld","year":"2016","journal-title":"Biophys Rev."},{"key":"2026072810084148300_cit40","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.jcis.2021.04.081","article-title":"Nanoparticle\nsize distribution quantification from\ntransmission electron microscopy (TEM) of ruthenium tetroxide stained\npolymeric nanoparticles","volume":"604","author":"Wilson","year":"2021","journal-title":"J. Colloid Interface\nSci."},{"issue":"6","key":"2026072810084148300_cit41","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1088\/0026-1394\/50\/6\/663","article-title":"Particle size distributions by transmission\nelectron microscopy: an interlaboratory comparison case study","volume":"50","author":"Rice","year":"2013","journal-title":"Metrologia"},{"issue":"2","key":"2026072810084148300_cit42","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/s41573-020-0090-8","article-title":"Engineering precision nanoparticles\nfor drug delivery","volume":"20","author":"Mitchell","year":"2021","journal-title":"Nat. Rev. Drug Discovery"},{"issue":"7","key":"2026072810084148300_cit43","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1039\/C8QM00078F","article-title":"Designed synthesis\nof organosilica nanoparticles for enzymatic biodiesel\nproduction","volume":"2","author":"Kalantari","year":"2018","journal-title":"Mater. Chem. Front."},{"key":"2026072810084148300_cit44","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/B978-0-12-817909-3.00010-8","article-title":"Chapter 10\n- Importance of Physicochemical Characterization of Nanoparticles\nin Pharmaceutical Product Development","volume-title":"Basic Fundamentals of Drug Delivery","author":"Raval","year":"2019"},{"issue":"2","key":"2026072810084148300_cit45","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1021\/ac0347718","article-title":"An Imprinted Organic\u2013Inorganic\nHybrid Sorbent\nfor Selective Separation of Cadmium from Aqueous Solution","volume":"76","author":"Lu","year":"2004","journal-title":"Anal. Chem."},{"key":"2026072810084148300_cit46","doi-asserted-by":"crossref","DOI":"10.1002\/0470011149","volume-title":"Infrared Spectroscopy:\nFundamentals and Applications","author":"Stuart","year":"2004"},{"issue":"1","key":"2026072810084148300_cit47","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/1477-3155-11-22","article-title":"Elastomeric\nmicroparticles for acoustic mediated bioseparations","volume":"11","author":"Johnson","year":"2013","journal-title":"J. Nanobiotechnol."},{"issue":"9\u201310","key":"2026072810084148300_cit48","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1515\/pac-2014-1117","article-title":"Physisorption of gases, with special\nreference to the evaluation of surface area and pore size distribution\n(IUPAC Technical Report)","volume":"87","author":"Thommes","year":"2015","journal-title":"Pure Appl. 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