{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:13:22Z","timestamp":1791292402608,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T00:00:00Z","timestamp":1684281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Princess Nourah bint Abdulrahman University Researchers","award":["PNURSP2023R199"],"award-info":[{"award-number":["PNURSP2023R199"]}]},{"name":"Princess Nourah bint Abdulrahman University Researchers","award":["MA-006"],"award-info":[{"award-number":["MA-006"]}]},{"name":"Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia","award":["PNURSP2023R199"],"award-info":[{"award-number":["PNURSP2023R199"]}]},{"name":"Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia","award":["MA-006"],"award-info":[{"award-number":["MA-006"]}]},{"name":"the Researchers Supporting program","award":["PNURSP2023R199"],"award-info":[{"award-number":["PNURSP2023R199"]}]},{"name":"the Researchers Supporting program","award":["MA-006"],"award-info":[{"award-number":["MA-006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Quercetin (QtN) displays low systemic bioavailability caused by poor water solubility and instability. Consequently, it exerts limited anticancer action in vivo. One solution to increase the anticancer efficacy of QtN is the use of appropriate functionalized nanocarriers that preferentially target and deliver the drug to the tumor location. Herein, a direct advanced method was designed to develop water-soluble hyaluronic acid (HA)-QtN-conjugated silver nanoparticles (AgNPs). HA-QtN reduced silver nitrate (AgNO3) while acting as a stabilizing agent to produce AgNPs. Further, HA-QtN#AgNPs served as an anchor for folate\/folic acid (FA) conjugated with polyethylene glycol (PEG). The resulting PEG-FA-HA-QtN#AgNPs (further abbreviated as PF\/HA-QtN#AgNPs) were characterized both in vitro and ex vivo. Physical characterizations included UV-visible (UV-Vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), particle size (PS) and zeta potential (ZP) measurements, and biopharmaceutical evaluations. The biopharmaceutical evaluations included analyses of the cytotoxic effects on the HeLa and Caco-2 cancer cell lines using the MTT assay; cellular drug intake into cancer cells using flow cytometry and confocal microscopy; and blood compatibility using an automatic hematology analyzer, a diode array spectrophotometer, and an enzyme-linked immunosorbent assay (ELISA). The prepared hybrid delivery nanosystem was hemocompatible and more oncocytotoxic than the free, pure QtN. Therefore, PF\/HA-QtN#AgNPs represent a smart nano-based drug delivery system (NDDS) and could be a promising oncotherapeutic option if the data are validated in vivo.<\/jats:p>","DOI":"10.3390\/molecules28104146","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T07:03:58Z","timestamp":1684393438000},"page":"4146","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Targeted Drug Administration onto Cancer Cells Using Hyaluronic Acid\u2013Quercetin-Conjugated Silver Nanoparticles"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2121-9269","authenticated-orcid":false,"given":"Rasha H.","family":"Al-Serwi","sequence":"first","affiliation":[{"name":"Department of Basic Dental Sciences, College of Dentistry, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5675-0842","authenticated-orcid":false,"given":"Mohamed A.","family":"Eladl","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0814-1743","authenticated-orcid":false,"given":"Mohamed","family":"El-Sherbiny","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh 11597, Saudi Arabia"},{"name":"Department of Anatomy and Embryology, Faculty of Medicine, Mansoura 35511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6405-6033","authenticated-orcid":false,"given":"Mohamed A.","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamal","family":"Othman","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh 11597, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6194-7092","authenticated-orcid":false,"given":"Sultan M.","family":"Alshahrani","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha 61441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha","family":"Alnefaie","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, Al-Baha University, Al Baha 65779, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afnan M.","family":"Jan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8678-5029","authenticated-orcid":false,"given":"Sulaiman M.","family":"Alnasser","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Unaizah Colleage of Pharmacy, Qassim University, Buraydah 52571, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7695-8691","authenticated-orcid":false,"given":"Aishah E.","family":"Albalawi","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, University of Tabuk, Tabuk 47913, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6362-8629","authenticated-orcid":false,"given":"Jamal Moideen Muthu","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Vaasudhara College of Pharmacy, Rajiv Gandhi University of Health Sciences, Sante Circle, Chintamani Road, Hoskote 562114, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0258-7322","authenticated-orcid":false,"given":"Farid","family":"Menaa","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Nanomedicine, California Innovations Corporation, San Diego, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41392-017-0004-3","article-title":"Controlled drug delivery vehicles for cancer treatment and their performance","volume":"3","author":"Senapati","year":"2018","journal-title":"Signal Transduct. 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