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Triple\u2010negative breast cancer (TNBC), the most aggressive subtype, has &lt;\u200915% 5\u2010year survival in metastatic cases, while conventional therapies are hampered by off\u2010target toxicity, multidrug resistance, and poor tumor accumulation (&lt;\u20090.7% injected dose per gram of tumor (ID\/g)). We present engineered exosomes as next\u2010generation Trojan horses for TNBC: NIR\u2010activatable photothermal agents (polydopamine, BPQDs, or ICG) are integrated into the membrane and chemotherapeutics or nucleic acids (doxorubicin, paclitaxel, siKRAS, siPD\u2010L1, miR\u2010145) encapsulated in the lumen. This \u201csmart\u201d platform exploits exosomes\u2019 natural tumor\u2010homing and immune\u2010evasive properties; a single low\u2010power 808\u2009nm laser pulse triggers mild hyperthermia (42\u00b0C\u201345\u00b0C), immunogenic cell death, and burst payload release, converting \u201ccold\u201d TNBC into \u201chot\u201d tumors. In orthotopic and metastatic 4T1\/MDA\u2010MB\u2010231 models, one intravenous dose plus 5\u2010min irradiation achieved a substantial tumor reduction in preclinical models, significant metastasis inhibition in murine models, long\u2010term memory immunity, and 15%\u201318% IDg tumor accumulation with negligible toxicity. Major challenges\u2014donor heterogeneity, low yields, rapid clearance, regulatory gaps, and limited NIR\u2010II probes\u2014are being overcome via single\u2010cell omics, advanced bioreactors, CD47\/PEGylation engineering, rigorous CMC standards, and PbS quantum dot loading. Future directions include AI\/CRISPR\u2010optimized design, NIR\u2010II platforms, checkpoint inhibitor synergy, with early\u2010stage clinical translation of photothermal and immunomodulatory exosome\u2010based therapeutics currently underway, highlighting their potential to advance precision oncology. \u201cHowever, challenges including scalability, batch variability, and regulatory standardization remain significant barriers to clinical translation.\u201d<\/jats:p>","DOI":"10.1002\/jbt.70971","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T10:33:23Z","timestamp":1781519603000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exosomes as Biomimetic Nanoplatforms for Synergistic Targeted Chemotherapy and Photothermal Treatment of Breast Cancer"],"prefix":"10.1002","volume":"40","author":[{"given":"Harsha","family":"Sanil","sequence":"first","affiliation":[{"name":"Department 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