Synthesis, optical properties, and biological applications of luminescent nanomaterials: Paradigm shift towards safer semiconductor quantum dots and nanoparticles

Quantum dots (QDs) are semiconductor nanocrystals (NCs) with excellent optical and electronic properties arising from strong exciton confinement. Their biomedical and technological potential have significantly contributed to nanotechnology. The QD field has evolved from traditional toxic heavy metal-based elements, such as Cd, Pb, Hg, chalcogens, and halogens, to a new focus on less-toxic alternatives from I-VI, III-V, and I-III-VI groups. Despite their attractive optical properties, the toxicity of conventional QDs limits their biomedical and clinical prospects. Recently, safer QDs based on chalcogenides of In, Ag, Ga, and Cu have been developed, offering absorption and emission in the biological I and II windows. Advances in synthesis, shell preparation, ligand exchange, and bioconjugation have further tailored these QDs for stable and specific applications, including targeted multimodal bioimaging, drug delivery, phototherapy, and image-guided therapy with high spatial, spectral, and temporal resolutions. This review highlights the transition from classical cadmium-, lead-, and mercury-based QDs to less-toxic silver-, copper-, and indium-based QDs for bioimaging and photodynamic therapy (PDT). First, we touch on classical developments in the synthesis, optical properties, and biological applications of heavy metals (Cd/Pb/Hg)-based QDs, before focusing the major parts on the synthesis, optical properties, bioconjugation, and bioimaging aspects of core only and core-shell nanomaterials from I-VI (Ag₂S, Ag₂Se, and Ag₂Te), III-V (GaN, GaP, GaAs, GaSb, InN, InP, InAs, and InSb), and I-III-VI (CuInS₂, CuInSe₂, CuInTe₂, CuGaS₂, CuGaSe₂, AgGaS₂, AgGaSe₂, AgInS₂, AgInSe₂, and AgInTe₂) groups. The discussion proceeds to the PDT potential of QDs, a minimally invasive method for treating cancers and infections that uses light-activated PSs to generate ROS, such as singlet oxygen (1O₂) and superoxide (O₂•⁻). We emphasize the importance of these nanomaterials over traditional organic PSs, such as porphyrins and phthalocyanines, which suffer from poor stability, narrow-band light absorption, and limited tissue penetration. Conversely, QDs offer broad and NIR light absorption, high photostability, and tunable surfaces for bioconjugation and targeted, image-guided therapy. The review highlights the mechanism and applications of III–V and I–III–VI QDs in tumor and infection treatment, while addressing challenges such as toxicity, hypoxia tolerance, and clinical translation toward multifunctional theragnostic systems, highlighting the pathway for safer, more versatile tools in clinical testing, imaging, and therapy, driving future innovations in healthcare.