Nanoparticles for chloroquine delivery: Enhancing its anticancer effect

Chloroquine (CQ) has gained attention in cancer therapy due to its ability to inhibit autophagy, modulate the tumor microenvironment, and reverse multidrug resistance. Several preclinical and clinical studies have demonstrated CQ’s anticancer activity and potential to enhance the efficacy of conventional chemotherapeutics. However, CQ’s clinical translation is hindered by its non-specific biodistribution, dose-limiting toxicity, and poor pharmacokinetics, which justify the development of nanoparticle (NP)-based drug delivery systems. Nanocarriers offer promising advantages, including improved drug stability without changing their physicochemical properties, controlled release, tumor-targeting ability, and enhanced permeability and retention effects. These properties can help overcome the limitations of CQ, maximizing its therapeutic benefits while minimizing systemic toxicity. In recent years, diverse CQ-loaded NP formulations have been developed, demonstrating enhanced tumor accumulation and improved cytotoxic effects. This review provides an overview of CQ’s role in cancer treatment, summarizing its mechanisms of action, reported clinical evidence, and associated limitations. Furthermore, this review focuses on the latest advancements in CQ-loaded nanoformulations, highlighting their advantages, challenges, and future perspectives in cancer therapy. • Chloroquine (CQ) shows potential in cancer therapy but has pharmacokinetic limitations. • Different nanoparticles (NPs) formulations were developed for CQ delivery. • NPs can enhance CQ bioavailability, tumor targeting, and reduce toxicity. • CQ-loaded NPs improve autophagy inhibition and multidrug resistance reversal.