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Current chemotherapeutic approaches are largely ineffective, thus calling for the development of alternative strategies to combat this disease. In this regard, numerous studies have reported the anticancer effect of flavonoids in different types of cancer. To enhance its therapeutic value, polymeric nanoparticles (PEG NPs) represent an ideal delivery system. Further, surface modification of NPs with PEG holds tremendous potential for improving the bioavailability and circulation time of native drugs in the blood. The present study aimed to develop Quercetin\/Rutin\u2010loaded PEG polymeric NPs (Qu\u2010PEG\/Ru\u2010PEG NPs) with enhanced encapsulation efficiency and sustained drug release. The synthesized Qu\u2010PEG NPs &amp; Ru\u2010PEG NPs were characterized by UV\u2010Vis Spectroscopy, FTIR spectrum, NMR, and XRD and SEM analysis. In\u2010vitro drug release study exhibited a cumulative release of Quercetin &amp; rutin for 24\u2009h at pH 7.4. Further, the polymeric nano\u2010formulations of Quercetin &amp; Rutin showed enhanced antioxidant activity, leading to defense against oxidative stress. In\u2010vitro cellular studies demonstrated that Qu\u2010PEG NPs and Ru\u2010PEG NPs significantly inhibit KB cell proliferation compared to free drugs alone. The current study also showed that Qu\u2010PEG NPs &amp; Ru\u2010PEG NPs enhance intracellular ROS generation compared to the drug alone. Hence, our research findings revealed that successful encapsulation of Quercetin &amp; Rutin in PEG NPs targets the tumor microenvironment and enhances the efficacy of drugs. Based on these preliminary results, flavonoid\u2010loaded polymeric\u2010based NPs might be potential therapeutic molecules against cancer in the future.<\/jats:p>","DOI":"10.1002\/jbt.70269","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T02:39:56Z","timestamp":1745462396000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Comparative Study of Quercetin\/Rutin Loaded PEG Polymeric Nanoparticles: Controlled Drug Release and Its Biological Activity"],"prefix":"10.1002","volume":"39","author":[{"given":"Renuka","family":"Mani","sequence":"first","affiliation":[{"name":"Department of Biochemistry, School of Bioscience Periyar University Salem Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swethaa Viswaresh","family":"Babu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Bioscience Periyar University Salem 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