Some key setbacks hinder green-synthesized QDs as safe, multifunctional, and effective cancer nanomedicines: lack of standardized synthesis protocols, batch-to-batch variability, limited long-term biosafety data, suboptimal targeting efficiency, and regulatory hurdles.
Abstract
The escalating global cancer burden, particularly in low- and middle-income countries, necessitates safer and more effective therapeutic strategies. The toxicity and environmental issues of traditional heavy-metal-based quantum dots (QDs) have been addressed by green-synthesised QDs, which have become a promising platform for nanomedicine. In photodynamic treatment (PDT), photothermal therapy (PTT), and theranostic applications, the anticancer effectiveness of green-synthesized QDs that are derived from plant extracts, microbes, biomolecules, and biomass waste is critically assessed. Green synthesis techniques, such as hydrothermal and microwave-assisted methods, provide biocompatible QDs with good photostability, tunable optical characteristics, and decreased cytotoxicity. Mechanistically, these QDs generate reactive oxygen species (ROS), induce mitochondrial dysfunction, produce localized hyperthermia upon near-infrared irradiation, and activate apoptotic pathways (such as p53, Bax/Bcl-2, and caspase cascade), leading to selective cancer cell death. Preclinical in vitro and in vivo studies demonstrate potent tumor ablation through passive (EPR effect) and active targeting strategies. Despite these advances, some key setbacks hinder their clinical translation: lack of standardized synthesis protocols, batch-to-batch variability, limited long-term biosafety data, suboptimal targeting efficiency, and regulatory hurdles. Future perspectives include AI-driven optimization, smart theranostic platforms integrating multimodal imaging and therapy, and sustainable circular economy approaches using biowaste. Addressing these challenges through harmonized protocols and rigorous preclinical validation will be essential to realize the full potential of green-synthesized QDs as safe, multifunctional, and effective cancer nanomedicines.
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