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Despite excellent cytocompatibility, porosity, and biodegradability of COFs, their practical implementations in nanomedicine have been limited due to low water dispersibility and poor processability into nanodimensions. There are limited reports on nanoscale covalent organic frameworks, which can exhibit excellent drug loading capacity and pH\u2010responsive drug release. Herein, a water\u2010dispersible 2D COF\u2010based nanocarrier is reported for pH\u2010responsive targeted delivery of therapeutics (doxorubicin) to cancer cells. Particularly, a hydrolytically susceptible boronate ester\u2010based covalent organic framework (COF\u20105) is supramolecularly stabilized with an amphiphilic polymer, Pluronic F127 (PLU), to obtain COF\u2010PLU nanoparticles with a size of ~185\u2009nm and a thickness of ~25\u2009nm. A high doxorubicin loading in the COF\u2010based nanocarrier (&gt;90% drug loading efficiency and ~35% drug loading capacity) and pH\u2010responsive drug release are observed. Furthermore, the surface modification of Dox\u2010loaded polymer\u2010stabilized COF\u20105 with hyaluronic acid demonstrates selective delivery of doxorubicin to cancer cells. Our study demonstrates a facile strategy for developing a pH\u2010responsive COF\u2010based nanocarrier with excellent drug\u2010loading capacity for targeted delivery of therapeutics to cancer cells.<\/jats:p>","DOI":"10.1002\/cmdc.70527","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:12:44Z","timestamp":1791526364000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["pH\u2010Responsive Covalent Organic Framework\u2010based Nanocarrier for Targeted Delivery of Cancer Therapeutics"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1410-9715","authenticated-orcid":false,"given":"Sukanya","family":"Bhunia","sequence":"first","affiliation":[{"name":"Department of Chemistry Sikkim Manipal Institute of Technology Sikkim Manipal University  Majitar Rangpo Sikkim India"},{"name":"Department of Biomedical Engineering Texas A&amp;M University  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