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To enhance biocompatibility and active targeting, nanoparticles were surface-coated with folic acid (FA), forming the RuPIP–Olap@ZIF-8-FA formulation. Rapid, eco-friendly fabrication produced high co-loading (20.59% ± 1.38% for RuPIP; 10.77% ± 1.00% for Olap). In vitro, FA-coated particles released 80% RuPIP and 99% Olap at pH 5.0, with much lower release at pH 7.4, and showed stronger cytotoxicity on MCF-7 and MDA-MB-231 cells. Embryo toxicity tests indicated reduced lethality (LC50 > 250 mg mL−1) and improved survivability (90%) with minimal malformations and no harmful aggregation, supporting clinical translation potential.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/evaluating-the-biological-characteristics-of-targeted-zif-8-encapsulated-individual-and-combined-drug-systems-for-enhanced-in-vivo-toxicity-mitigation-using-folic-acid-ligands/443993/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/evaluating-the-biological-characteristics-of-targeted-zif-8-encapsulated-individual-and-combined-drug-systems-for-enhanced-in-vivo-toxicity-mitigation-using-folic-acid-ligands/443993.png","ImageObject",300,407,{"name":92,"@type":93},"Fahsai","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-03","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What drug delivery system is developed in this study?","Question",{"text":112,"@type":113},"A pH-responsive ZIF-8 nanoparticle system is constructed to co-deliver RuPIP and olaparib, with a folic acid surface coating for targeted delivery (RuPIP–Olap@ZIF-8-FA).","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the formulation respond to pH in vitro?",{"text":117,"@type":113},"The FA-coated dual-drug system shows pH-responsive release: at pH 5.0 it releases about 80% RuPIP and 99% Olap, compared with much lower release at pH 7.4 over 48 hours.",{"name":119,"@type":110,"acceptedAnswer":120},"What biological results support enhanced safety and targeting?",{"text":121,"@type":113},"FA-coated nanoparticles increase cytotoxicity against MCF-7 and MDA-MB-231 cells while embryo studies show reduced lethality (LC50 > 250 mg mL−1) and improved survivability (90%) up to 120 h, with no significant malformations or aggregation issues.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},443993,1790890613,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":31},549768702563,"https://ap-avatar.wpscdn.com/avatar/8000c4aa63b76e948b?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786536092046926083","RSC Advances  \nPAPER  \nCite this: RSC Adv., 2026, 16, 1912  \nReceived 10th October 2025 Accepted 15th December 2025 DOI: 10.1039/d5ra07756g  \n[rsc.li/rsc-advances](rsc.li/rsc-advances)  \nEvaluating the biological characteristics of targeted ZIF-8-encapsulated individual and combined drug systems for enhanced in vivo toxicity mitigation using folic acid ligands  \nNoor S. Sadeq,  *ab Mas Jaffri Masarudin,cd Mohd Basyaruddin Abdul Rahman, ef Suet Lin Chia,fg Syahida Ahmadh and Haslina Ahmad  *af  \nThe management of toxicity, and the fulfillment of safety requirements are considered as the most prominent challenges associated with cancer drug delivery. This study introduces a novel pH-responsive nanoparticle system based on ZIF-8 for the co-delivery of a ruthenium(II) polypyridyl complex (RuPIP) and olaparib (Olap), which is designed for enhanced therapeutic efficacy and reduced systematic toxicity. To improve their biocompatibility and targeting, the nanoparticles were surface-coated with folic acid ligand, yielding the final RuPIP–Olap@ZIF-8-FA formulation. The RuPIP–Olap@ZIF-8 nanoparticles were fabricated through a rapid, eco-friendly method, and they achieved high co-loading capacities of 20 .59% ± 1.38% for RuPIP and 10 .77% ± 1. 00% for Olap, as confirmed by HPLC analysis. In vitro, the FA-coated dual-drug system exhibited clear pH-responsive behaviour, releasing 80% of RuPIP and 99% of Olap at pH 5.0, compared with 32% and 29%, respectively, at pH 7 .4 within 48 hours. The FA-coated RuPIP–Olap@ZIF-8 system also showed markedly enhanced cytotoxicity against the MCF-7 and MDA-MB-231 cell lines, reducing the cell viability to 11 .38% and 13 .48%, respectively. In comparison to the non-coated dual-drug system, the FA-coated dual-drug system did not induce lethality to 75% of embryos (LC50 > 250 mg mL−1) with significant improved survivability (90%) until 120 h of incubation. Results showed that RuPIP– Olap@ZIF8-FA did not cause significant malformations, even at elevated concentrations, and did not present aggregation issues toward healthy embryos. These findings establish RuPIP–Olap@ZIF-8-FA asa promising dual-drug nanocarrier capable of targeted delivery, pH-triggered release, and distinct therapeutic pathways. Its high loading efficiency, simplicity, and improved safety profile highlight its strong potential for advancement toward clinical translation.  \n1 Introduction  \naDepartment of Chemistry, Faculty of Science, Universiti Putra Malaysia, UPM, 43400 Serdang, Selangor, Malaysia. E-mail: [haslina_ahmad@upm.edu.my](haslina_ahmad@upm.edu.my); noor.s.sadeq@ [uotechnology.edu.iq](uotechnology.edu.iq)  \nbMedical & Industrial Materials Branch, Applied Science Department, University of Technology, Baghdad, Iraq  \ncDepartment of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia dNanomaterials Synthesis and Characterisation Laboratory, Institute of Nanoscience and Nanotechnology, Universiti Putra Malaysia, Selangor, Malaysia  \neIntegrated Chemical BioPhysics Research, Faculty of Science, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia  \nfUPM-MAKNA Cancer Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia  \ngDepartment of Microbiology, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, UPM, 43400 Serdang, Selangor, Malaysia  \nhDepartment of Biochemistry, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, UPM, 43400 Serdang, Selangor, Malaysia  \nCombination therapy has emerged as a cornerstone in modern cancer management, offering signi􀀁cant advantages over monotherapy, which o􀀁en suffers from limited efficacy and rapid development of drug resistance. By co-administering two or more therapeutic agents with distinct mechanisms of action, combination therapy can produce synergistic anticancer effects, reduce the required dose of individual drug","cbCaivqMQG4zLFCj","https://ap.wps.com/l/cbCaivqMQG4zLFCj","pdf",5547459,"English","# Introduction\n## Cancer drug delivery challenges and combination therapy\n## Metal–organic frameworks (MOFs) as drug delivery platforms\n## pH sensitivity and tumor microenvironment-triggered release","[{\"question\":\"What drug delivery system is developed in this study?\",\"answer\":\"A pH-responsive ZIF-8 nanoparticle system is constructed to co-deliver RuPIP and olaparib, with a folic acid surface coating for targeted delivery (RuPIP–Olap@ZIF-8-FA).\"},{\"question\":\"How does the formulation respond to pH in vitro?\",\"answer\":\"The FA-coated dual-drug system shows pH-responsive release: at pH 5.0 it releases about 80% RuPIP and 99% Olap, compared with much lower release at pH 7.4 over 48 hours.\"},{\"question\":\"What biological results support enhanced safety and targeting?\",\"answer\":\"FA-coated nanoparticles increase cytotoxicity against MCF-7 and MDA-MB-231 cells while embryo studies show reduced lethality (LC50 \\u003e 250 mg mL−1) and improved survivability (90%) up to 120 h, with no significant malformations or aggregation issues.\"}]","Evaluating the biological characteristics of targeted ZIF-8-encapsulated individual and combined drug systems for enhanced in vivo toxicity mitigation using folic acid ligands | PDF",1790706361]