Evaluating the biological characteristics of targeted ZIF-8-encapsulated individual and combined drug systems for enhanced in vivo toxicity mitigation using folic acid ligands

Sep 29, 2026

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The study addresses toxicity and safety challenges in cancer drug delivery by developing a pH-responsive ZIF-8 nanoparticle platform for co-delivery of a ruthenium(II) polypyridyl complex (RuPIP) and olaparib (Olap). 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.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Introduction

Cancer drug delivery challenges and combination therapy

Metal–organic frameworks (MOFs) as drug delivery platforms

pH sensitivity and tumor microenvironment-triggered release

RSC Advances PAPER Cite this: RSC Adv., 2026, 16, 1912 Received 10th October 2025 Accepted 15th December 2025 DOI: 10.1039/d5ra07756g [rsc.li/rsc-advances](rsc.li/rsc-advances) Evaluating the biological characteristics of targeted ZIF-8-encapsulated individual and combined drug systems for enhanced in vivo toxicity mitigation using folic acid ligands Noor S. Sadeq, *ab Mas Jaﬀri Masarudin,cd Mohd Basyaruddin Abdul Rahman, ef Suet Lin Chia,fg Syahida Ahmadh and Haslina Ahmad *af The 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. 1 Introduction aDepartment 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) bMedical & Industrial Materials Branch, Applied Science Department, University of Technology, Baghdad, Iraq cDepartment 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 eIntegrated Chemical BioPhysics Research, Faculty of Science, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia fUPM-MAKNA Cancer Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia gDepartment of Microbiology, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, UPM, 43400 Serdang, Selangor, Malaysia hDepartment of Biochemistry, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, UPM, 43400 Serdang, Selangor, Malaysia Combination 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

FAQs

What drug delivery system is developed in this study?

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).

How does the formulation respond to pH in vitro?

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.

What biological results support enhanced safety and targeting?

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.

Sep 29, 2026

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