{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:05:33Z","timestamp":1789099533870,"version":"build-2803163510"},"reference-count":30,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2019YFA0210104"],"award-info":[{"award-number":["2019YFA0210104"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32401258"],"award-info":[{"award-number":["32401258"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32401258"],"award-info":[{"award-number":["32401258"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011791","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20230837"],"award-info":[{"award-number":["BK20230837"]}],"id":[{"id":"10.13039\/501100011791","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Triple-negative breast cancer (TNBC), devoid of actionable targets for endocrine or HER2-directed therapy, is highly aggressive with elevated risks of recurrence and metastasis; surgical resection remains the mainstay of treatment, and postoperative chemotherapy serves as a key adjuvant modality for controlling residual disease. Doxorubicin (DOX), although widely used, shows limited tumor selectivity, considerable systemic toxicity, and poor control over drug release at the tumor site. To address these issues, we developed near-infrared (NIR)-responsive gold-decorated phase-change nanodroplets (AuNPs-DOX-NDs) that combine photothermal conversion, liquid-to-gas phase transition, and controlled DOX release in a single platform. Methods: The nanodroplets consisted of a perfluorohexane (PFH) core, a DOX-loaded lipid shell, and polyethyleneimine-modified gold nanoparticles (PEI-AuNPs) conjugated to the surface as the NIR photothermal component. Physicochemical characterization was performed to evaluate morphology, colloidal dispersity, and storage stability. Under 808 nm laser irradiation, the photothermal behavior, PFH vaporization, and DOX release properties of AuNPs-DOX-NDs were investigated. In vitro studies using 4T1 TNBC cells were conducted to assess intracellular DOX accumulation, cell proliferation, migration, and apoptosis. Results: Physicochemical characterization showed that the nanodroplets had a uniform nanoscale morphology, good colloidal dispersity, and acceptable storage stability. Under 808 nm laser irradiation, AuNPs-DOX-NDs exhibited concentration-dependent photothermal heating, which induced PFH vaporization and accelerated DOX release, indicating a clear stimulus-responsive release behavior. In vitro studies using 4T1 TNBC cells showed enhanced intracellular DOX accumulation after treatment with AuNPs-DOX-NDs. Upon laser irradiation, the nanodroplets further inhibited cell proliferation and migration and promoted apoptosis, suggesting an enhanced combined photothermal\u2013chemotherapeutic effect in 4T1 TNBC cells. Conclusions: These results indicate that AuNPs-DOX-NDs may serve as a useful NIR-responsive platform for externally controlled drug release and enhanced combined photothermal-chemotherapy, and deserve further evaluation in vivo.<\/jats:p>","DOI":"10.3390\/pharmaceutics18070816","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:06:34Z","timestamp":1782875194000},"page":"816","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["NIR-Responsive Gold-Decorated Phase-Change Nanodroplets for Photothermal-Triggered Pulsatile Doxorubicin Release and Enhanced Combined Photothermal-Chemotherapy in Triple-Negative Breast Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Luyao","family":"Ma","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulai","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghao","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwei","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Duan","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1016\/S0140-6736(20)32381-3","article-title":"Breast cancer","volume":"397","author":"Loibl","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"265","DOI":"10.2147\/BCTT.S516542","article-title":"Diagnosis, Prognosis, and Treatment of Triple-Negative Breast Cancer: A Review","volume":"17","author":"Jie","year":"2025","journal-title":"Breast Cancer Targets Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e071674","DOI":"10.1136\/bmj-2022-071674","article-title":"Advances in systemic therapies for triple negative breast cancer","volume":"381","author":"Goetz","year":"2023","journal-title":"BMJ"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s13045-023-01497-3","article-title":"Recent advances in targeted strategies for triple-negative breast cancer","volume":"16","author":"Zhu","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41571-021-00565-2","article-title":"Treatment landscape of triple-negative breast cancer\u2014Expanded options, evolving needs","volume":"19","author":"Bianchini","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s11671-024-04086-6","article-title":"Enhanced drug delivery with nanocarriers: A comprehensive review of recent advances in breast cancer detection and treatment","volume":"19","author":"Dhiman","year":"2024","journal-title":"Discov. Nano"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"107534","DOI":"10.1016\/j.phrs.2024.107534","article-title":"Targeted and cytotoxic inhibitors used in the treatment of breast cancer","volume":"210","author":"Roskoski","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mishra, G., Leharwani, M., Alqahtani, T., Al Shmrany, H., Gupta, G., Sahebkar, A., Patil, U.K., and Kesharwani, P. (2026). Multifunctional chitosan-doxorubicin nanocarriers: Advancing targeted breast cancer chemotherapy. Mol. Cancer, 25.","DOI":"10.1186\/s12943-026-02639-0"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1002\/jat.70131","article-title":"Doxorubicin-Induced Cardiotoxicity: Comprehensive Pathway Insights and Advanced Preclinical Therapeutics","volume":"46","author":"Sharma","year":"2026","journal-title":"J. Appl. Toxicol."},{"key":"ref_10","first-page":"445","article-title":"Enhancing drug penetration in solid tumors via nanomedicine: Evaluation models, strategies and perspectives","volume":"32","author":"Shen","year":"2024","journal-title":"Bioact. Mater."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1016\/j.ultrasmedbio.2021.04.003","article-title":"Functional ultrasound-triggered phase-shift perfluorocarbon nanodroplets for cancer therapy","volume":"47","author":"Guo","year":"2021","journal-title":"Ultrasound Med. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3390\/pharmaceutics16010051","article-title":"Effect of Phase-Change Nanodroplets and Ultrasound on Blood-Brain Barrier Permeability In Vitro","volume":"16","author":"Vlatakis","year":"2023","journal-title":"Pharmaceutics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"42128","DOI":"10.1021\/acsnano.5c12290","article-title":"Double-Emulsion Perfluorocarbon Nanodroplets for Ultrasound and Photoacoustic Image-Guided Drug Delivery and Release","volume":"19","author":"Chung","year":"2025","journal-title":"ACS Nano"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e06806","DOI":"10.1002\/smll.202506806","article-title":"Precision mRNA Delivery via Ultrasound-Controlled Release Perfluorocarbon Emulsions: An Innovative Ultrasound Theranostic Strategy with (19)F MRI Feasibility","volume":"22","author":"Liu","year":"2026","journal-title":"Small"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"124952","DOI":"10.1016\/j.ijpharm.2024.124952","article-title":"Combination of gold nanoparticles with near-infrared light as an alternative approach for melanoma management","volume":"668","author":"Lopes","year":"2025","journal-title":"Int. J. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"417","DOI":"10.3390\/nano16070417","article-title":"Upconverting Nanoparticles Functionalized with Protein-Gold Nanoclusters and Chlorin e6 for Near-Infrared-Activated Photodynamic Therapy","volume":"16","author":"Poderys","year":"2026","journal-title":"Nanomater."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/s41392-023-01642-x","article-title":"Smart nanoparticles for cancer therapy","volume":"8","author":"Sun","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5195","DOI":"10.1021\/acs.chemrev.4c00835","article-title":"Molecular Gold Nanoclusters for Advanced NIR-II Bioimaging and Therapy","volume":"125","author":"Baghdasaryan","year":"2025","journal-title":"Chem. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41392-025-02536-w","article-title":"Nanoparticles-based phototherapy systems: Molecular mechanisms and clinical applications","volume":"11","author":"Chauhan","year":"2026","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1186\/s13046-019-1443-1","article-title":"Recent advances in nanotheranostics for triple negative breast cancer treatment","volume":"38","author":"Thakur","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3636","DOI":"10.1021\/jp064341w","article-title":"Microscale Heat Transfer Transduced by Surface Plasmon Resonant Gold Nanoparticles","volume":"111","author":"Roper","year":"2007","journal-title":"J. Phys. Chem. C Nanomater. Interfaces"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e70733","DOI":"10.1002\/mco2.70733","article-title":"Targeted Therapies for Each Subtype of Breast Cancer","volume":"7","author":"Liu","year":"2026","journal-title":"MedComm (2020)"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"36323","DOI":"10.1021\/acsnano.5c09413","article-title":"Spatiotemporally Controlled Nanomicelles for Synergistic Phototherapy and Immune Reprogramming in Triple-Negative Breast Cancer","volume":"19","author":"Chang","year":"2025","journal-title":"ACS Nano"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/wnan.1176","article-title":"Phase-shift, stimuli-responsive perfluorocarbon nanodroplets for drug delivery to cancer","volume":"4","author":"Rapoport","year":"2012","journal-title":"Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cis.2016.08.007","article-title":"On the thermodynamics and kinetics of superheated fluorocarbon phase-change agents","volume":"237","author":"Mountford","year":"2016","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1109\/TNB.2025.3644373","article-title":"Gold Nanoparticle Coating Reduces Acoustic Pressure Threshold for Perfluorohexane Nanodroplet Vaporization: Potential Mechanisms and Therapy Implications","volume":"25","author":"Mistry","year":"2026","journal-title":"IEEE Trans. Nanobiosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1039\/C8TB03056A","article-title":"Hyaluronic acid and polydopamine functionalized phase change nanoparticles for ultrasound imaging-guided photothermal-chemotherapy","volume":"7","author":"Mou","year":"2019","journal-title":"J. Mater. Chem. B"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1080\/17425247.2022.2134853","article-title":"Stimuli-responsive image-guided nanocarriers as smart drug delivery platforms","volume":"19","author":"Chen","year":"2022","journal-title":"Expert. Opin. Drug Deliv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e13457","DOI":"10.1002\/smll.202513457","article-title":"Photothermal Nanoswitches Enable Precision Modulation of Paradoxical Signaling Pathways for Targeted Therapy","volume":"22","author":"Fang","year":"2026","journal-title":"Small"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"114839","DOI":"10.1016\/j.colsurfb.2025.114839","article-title":"Dual-responsive zwitterionic nanogels with synergistic charge reversal and hypoxia-activated drug release for precise tumor targeting and enhanced chemotherapy","volume":"254","author":"Liao","year":"2025","journal-title":"Colloids Surf. B Biointerfaces"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/7\/816\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T04:26:13Z","timestamp":1783052773000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/7\/816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":30,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["pharmaceutics18070816"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18070816","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]}}}