{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:12:10Z","timestamp":1788862330005,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangdong Provincial Department of Education Ordinary Universities Characteristic Innovation Project","award":["2020KTSCX158"],"award-info":[{"award-number":["2020KTSCX158"]}]},{"name":"Guangdong Technology and Equipment Research Center for Soil and Water Pollution Control","award":["2018H014"],"award-info":[{"award-number":["2018H014"]}]},{"DOI":"10.13039\/501100011275","name":"Guangdong Provincial Key Laboratory of Environmental Health and Land Resource","doi-asserted-by":"publisher","award":["2020B121201014"],"award-info":[{"award-number":["2020B121201014"]}],"id":[{"id":"10.13039\/501100011275","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2020B121201014"],"award-info":[{"award-number":["2020B121201014"]}],"id":[{"id":"https:\/\/ror.org\/0590fg074","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Zhaoqing University","award":["gcc202601"],"award-info":[{"award-number":["gcc202601"]}]},{"award":["gcc202601"],"award-info":[{"award-number":["gcc202601"]}],"id":[{"id":"https:\/\/ror.org\/025n5kj18","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>Polymeric micelles represent a fundamental self-assembled architecture of gel-based soft materials and have emerged as promising nanocarriers for anticancer drug delivery. Their performance is largely governed by the block composition of constituent copolymers, and understanding their self-assembly behavior provides critical insights into the rational design of gel-related drug delivery systems. In this work, dissipative particle dynamics (DPD) simulations were performed to systematically investigate two types of mixed drug-loaded micellar systems self-assembled from a triblock copolymer mPEG-b-poly(2-(diethylamino)ethyl methacrylate)-b-PMMA (PDEAEMA, hereafter referred to as the DMA block for brevity) with either a diblock copolymer PDEAEMA-b-PMMA (polymer B) or PPEGMA-b-PDEAEMA (polymer C). By tailoring the ratios of hydrophobic (MMA, the constituent block of PMMA) and pH-sensitive (DMA) blocks, the protonation-responsive behavior, structural stability, drug loading capacity, and release kinetics of the micelles were comprehensively examined. The simulation results demonstrate that: (1) increasing the hydrophobic block ratio accelerates the protonation-triggered micellar swelling and drug release because the increased hydrophobic content enhances the core compactness which, upon protonation, generates a stronger driving force for chain extension, yet an optimal ratio (+16 MMA units) exists beyond which excessive hydrophobic blocks suppress release due to core densification; (2) increasing the pH-sensitive block ratio significantly enhances the maximum drug loading capacity (from 9.83% to 12.22% for the A\/C system), but exerts only limited influence on the release rate; (3) the A\/C mixed micelles with higher PEG content exhibit superior structural stability and drug loading capacity, while the A\/B system with higher MMA content displays more sensitive pH-responsiveness. These findings reveal a competing mechanism between \u201cprotonation-driven force\u201d and \u201cstructural resistance,\u201d providing mesoscopic theoretical guidance for the rational design of pH-responsive polymeric nanocarriers and self-assembled soft materials via block ratio modulation.<\/jats:p>","DOI":"10.3390\/gels12090823","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:02:24Z","timestamp":1788858144000},"page":"823","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["pH-Responsive Mixed Polymeric Micelles as Gel-Related Nanocarriers for Drug Delivery: A DPD Study on Block Ratio Modulation"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1498-0428","authenticated-orcid":false,"given":"Wensheng","family":"Wu","sequence":"first","affiliation":[{"name":"School of Environmental and Chemical Engineering, Zhaoqing University, Zhaoqing 526061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7962-7636","authenticated-orcid":false,"given":"Zhiwei","family":"Li","sequence":"additional","affiliation":[{"name":"School of Environmental and Chemical Engineering, Zhaoqing University, Zhaoqing 526061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Environmental and Chemical Engineering, Zhaoqing University, Zhaoqing 526061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyuan","family":"Zeng","sequence":"additional","affiliation":[{"name":"School of Environmental and Chemical Engineering, Zhaoqing University, Zhaoqing 526061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimao","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Environmental and Chemical Engineering, Zhaoqing University, Zhaoqing 526061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Environmental and Chemical Engineering, Zhaoqing University, Zhaoqing 526061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jconrel.2015.08.050","article-title":"Stimuli-responsive nanoparticles for targeting the tumor microenvironment","volume":"219","author":"Du","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.addr.2012.09.026","article-title":"Advanced drug delivery devices via self-assembly of amphiphilic block copolymers","volume":"64","author":"Vandermeulen","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.jconrel.2008.07.004","article-title":"Hydrotropic polymer micelles containing acrylic acid moieties for oral delivery of paclitaxel","volume":"132","author":"Kim","year":"2008","journal-title":"J. Control. Release"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.ejps.2012.12.006","article-title":"A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics","volume":"48","author":"Steichen","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1007\/s11095-010-0233-4","article-title":"Polymeric micelles in anticancer therapy: Targeting, imaging and triggered release","volume":"27","author":"Oerlemans","year":"2010","journal-title":"Pharm. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.biomaterials.2012.08.072","article-title":"pH-sensitive poly(histidine)-PEG\/DSPE-PEG copolymer micelles for cytosolic drug delivery","volume":"34","author":"Wu","year":"2013","journal-title":"Biomaterials"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Luo, Y.L., Yin, X.J., Yin, X., Chen, A.Q., Zhao, L.L., Zhang, G., Liao, W.B., Huang, X.X., Li, J., and Zhang, C.Y. (2019). Dual pH\/redox-responsive mixed polymeric micelles for anticancer drug delivery and controlled release. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11040176"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1021\/acs.biomac.4c01202","article-title":"Fabrication of pH- and ultrasound-responsive polymeric micelles: The effect of amphiphilic block copolymers with different hydrophilic\/hydrophobic block ratios for self-assembly and controlled drug release","volume":"26","author":"Wei","year":"2025","journal-title":"Biomacromolecules"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5993","DOI":"10.1016\/S0032-3861(01)00066-0","article-title":"Synthesis and aqueous solution properties of near-monodisperse tertiary amine methacrylate homopolymers and diblock copolymers","volume":"42","author":"Armes","year":"2001","journal-title":"Polymer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8508","DOI":"10.1021\/acs.biomac.5c01343","article-title":"Polyzwitterion-Based pH-Responsive Shell of Polymeric Micelle: Evaluation of Physicochemical Properties and In Vivo Functionalities","volume":"26","author":"Chintrakulchai","year":"2025","journal-title":"Biomacromolecules"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4423","DOI":"10.1063\/1.474784","article-title":"Dissipative particle dynamics: Bridging the gap between atomistic and mesoscopic simulation","volume":"107","author":"Groot","year":"1997","journal-title":"J. Chem. Phys."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8713","DOI":"10.1063\/1.476300","article-title":"Dynamic simulation of diblock copolymer microphase separation","volume":"108","author":"Groot","year":"1998","journal-title":"J. Chem. Phys."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8224","DOI":"10.1039\/c1sm05667k","article-title":"Mesoscopic simulation of the drug release mechanism on the polymeric vehicle P(ST-DVB) in an acid environment","volume":"7","author":"Vicente","year":"2011","journal-title":"Soft Matter"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Yang, C.F., Liu, W.Y., Xiao, J.Y., Yuan, C., Chen, Y.X., Guo, J.W., Yue, H.B., Zhu, D.Y., Lin, W.J., and Tang, S.Q. (2020). PH-sensitive mixed micelles assembled from PDEAEMA-PPEGMA and PCL-PPEGMA for doxorubicin delivery: Experimental and DPD simulations study. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12020170"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12458","DOI":"10.1039\/D2CP04045J","article-title":"Folate modified dual pH\/reduction-responsive mixed micelles assembled using FA-PEG-PDEAEMA and PEG-SS-PCL for doxorubicin delivery","volume":"25","author":"Yang","year":"2023","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1039\/D3CP04190E","article-title":"A dissipative particle dynamics simulation of controlled loading and responsive release of theranostic agents from reversible crosslinked triblock copolymer vesicles","volume":"26","author":"Wang","year":"2024","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1080\/19475411.2025.2482923","article-title":"Computer simulation of a pH-responsive drug delivery system formed by \u03bc-ABC miktoarm star polymers in aqueous solution","volume":"16","author":"Ma","year":"2025","journal-title":"Int. J. Smart Nano Mater."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"131436","DOI":"10.1016\/j.ijbiomac.2024.131436","article-title":"Assessing the structural stability and drug encapsulation efficiency of poly(ethylene glycol)-poly(L-lactic acid) nanoparticles loaded with atorvastatin calcium: Based on dissipative particle dynamics","volume":"267","author":"Feng","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1021\/acs.jpcb.4c00230","article-title":"Co-assembly of amphiphilic triblock copolymers with nanodrugs and drug release kinetics in solution","volume":"128","author":"Zhou","year":"2024","journal-title":"J. Phys. Chem. B"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jcis.2011.08.028","article-title":"Self-assembly of pH-sensitive mixed micelles based on linear and star copolymers for drug delivery","volume":"364","author":"Huang","year":"2011","journal-title":"J. Colloid Interface Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"25592","DOI":"10.1021\/acsami.5b08366","article-title":"Mesoscale simulations and experimental studies of pH-sensitive micelles for controlled drug delivery","volume":"7","author":"Wang","year":"2015","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6857","DOI":"10.2147\/IJN.S143927","article-title":"Poly(2-(diethylamino)ethyl methacrylate)-based, pH-responsive, copolymeric mixed micelles for targeting anticancer drug control release","volume":"12","author":"Chen","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_23","first-page":"1702","article-title":"Folate-modified pH-responsive copolymer mixed micelles for anticancer drug delivery","volume":"76","author":"Zhao","year":"2025","journal-title":"CIESC J."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Malo de Molina, P., and Gradzielski, M. (2017). Gels Obtained by Colloidal Self-Assembly of Amphiphilic Molecules. Gels, 3.","DOI":"10.3390\/gels3030030"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sipos, B., Budai-Sz\u0171cs, M., Katona, G., and Cs\u00f3ka, I. (2025). Gellan Gum-Based In Situ Hydrogels for Nasal Delivery of Polymeric Micelles Loaded with Risperidone. Gels, 11.","DOI":"10.3390\/gels11060404"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0006-3495(01)75737-2","article-title":"Mesoscopic simulation of cell membrane damage, morphology change and rupture by nonionic surfactants","volume":"81","author":"Groot","year":"2001","journal-title":"Biophys. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1039\/C1SM06378B","article-title":"Dissipative particle dynamics study on the mesostructures of n-octadecane\/water emulsion with alternating styrene\u2013maleic acid copolymers as emulsifier","volume":"8","author":"Lin","year":"2012","journal-title":"Soft Matter"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1021\/jp211056p","article-title":"Mesoscale simulation of the effect of a lactide segment on the nanostructure of star poly(ethylene glycol-co-lactide)-acrylate macromonomers in aqueous solution","volume":"116","author":"Moeinzadeh","year":"2012","journal-title":"J. Phys. Chem. B"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.jconrel.2012.06.027","article-title":"pH-sensitive drug loading\/releasing in amphiphilic copolymer PAE-PEG: Integrating molecular dynamics and dissipative particle dynamics simulations","volume":"162","author":"Luo","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1007\/s11051-014-2403-5","article-title":"Dissipative particle dynamics simulation on drug loading\/release in polyester-PEG dendrimer","volume":"16","author":"Wen","year":"2014","journal-title":"J. Nanopart. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.progpolymsci.2012.07.002","article-title":"Design and development of polymeric micelles with cleavable links for intracellular drug delivery","volume":"38","author":"Wei","year":"2013","journal-title":"Prog. Polym. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15419","DOI":"10.1021\/acsomega.5c00083","article-title":"Study on the self-assembly behavior of polycaprolactone star-shaped copolymers based on dissipative particle dynamics","volume":"10","author":"Pan","year":"2025","journal-title":"ACS Omega"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"138525","DOI":"10.1016\/j.jcis.2025.138525","article-title":"Dissipative particle dynamics as a computational tool to detect the morphology-rheology interplay in Pluronic F68\/water mixtures: A promising drug carrier","volume":"700","author":"Lauriello","year":"2025","journal-title":"J. Colloid Interface Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"17668","DOI":"10.1021\/am503920m","article-title":"Drug Release from pH-Sensitive Polymeric Micelles with Different Drug Distributions: Insight from Coarse-Grained Simulations","volume":"6","author":"Nie","year":"2014","journal-title":"ACS Appl. Mater. Interfaces"}],"container-title":["Gels"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2310-2861\/12\/9\/823\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:27:53Z","timestamp":1788859673000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2310-2861\/12\/9\/823"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":34,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["gels12090823"],"URL":"https:\/\/doi.org\/10.3390\/gels12090823","relation":{},"ISSN":["2310-2861"],"issn-type":[{"value":"2310-2861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]}}}