Introduction

Nanotechnology is a multidisciplinary field encompassing the design, manipulation and characterization of structures, devices and microenvironments at the nanoscale [1,2]. Materials are generally classified as nanomaterials if at least one of their dimensions is below 100 nm [1,3], though some authors extend this definition to structures up to 300 nm, depending on the specific field of application [4,5]. Nanotechnology has diverse applications across multiple sectors, including agriculture [6], fossil fuel extraction [7], renewable energy [8,9], textiles [10], waste management [11,12], food production [13], construction materials [14] and biomedicine [15].

Although archaeological evidence indicates that humans have utilized and harnessed the properties of nanomaterials for at least 4,500 years [2,3], modern nanotechnology is generally traced back to 1959 when Richard Feynman, later awarded the 1965 Nobel Prize in Physics, argued in his seminar lecture, "There's Plenty of Room at the Bottom” [16] that the fundamental laws of nature do not restrict our ability to manipulate matter at the atomic and molecular scale; rather, the limitation lies in the absence of suitable tools and techniques [3]. Indeed, over the past six decades, advancements in instrumentation have propelled nanotechnology into a rapidly expanding scientific discipline [17]. Figure 1 highlights some of the most significant milestones in the evolution of modern nanotechnology.

Figure 1.: Key milestones in the history of modern nanotechnology. Following the conceptualization of nanotechnology in the 1960s, the synthesis of various nanomaterials over the next decades marked significant advancements in the field. These developments enabled diverse biomedical applications, including contrast agents, nanoconstruct-based chemotherapy and, more recently, nanoparticle-based vaccine delivery against SARS-CoV-2. Adapted from [17] under the Creative Commons Attribution 4.0 International License (CC BY 4.0), with additional modifications based on the literature reviewed in this work

Consistently, nanotechnology has emerged as a promising approach for developing advanced drug delivery systems. From the early use of liposomes in the 1960s to modern nucleic acid delivery platforms, nanotechnology has proven its value not only in drug delivery and diagnostics but also in clinical applications. A major milestone in nanomedicine was the U.S. Food and Drug Administration’s (FDA) 1998 approval of Doxil®, a liposomal formulation of doxorubicin initially indicated for Kaposi’s sarcoma [2]. Encapsulation enhanced its pharmacokinetic profile, improving safety and efficacy over free doxorubicin [18,19]. More recently, the clinical success of therapeutics based on small interfering RNA (siRNA) [20,21], gene-editing treatments [22,23], and messenger RNA (mRNA) vaccines for COVID-19 [24] underscores the transformative role of nanotechnology in modern medicine. Besides drug delivery, nanotechnology has demonstrated considerable potential in biosensors, tissue engineering, nanobiotechnology, and diagnostic tool development [25].

Through precise engineering, nanotechnology facilitates the combination of therapies, the circumvention of biological barriers and the controlled modification of drug properties [26]. As a result, nanoengineered systems improve drug stability and extend circulation time in the body [27]. Additionally, nanomedicine formulations allow precise control over dosage, accumulation and, in some cases, drug release site [25,27]. Integrating biofunctional structures into nanomaterials enables active targeting toward specific cells or tissues [28,29]. The biomedical impact of nanotechnology stems from its functional characteristics, which align with biological processes occurring at the nanoscale [30].

Nanoparticles have demonstrated their ability to transport a wide range of molecules, from small molecules to proteins and nucleic acids [31,32], as well as hybrid drug-diagnostic systems [33,34]. This versatility has enabled their investigation for multiple preclinical applications, reinforcing nanotechnology’s promise in biomedical development. Nanomaterial-based delivery systems have been most extensively applied in oncology [26], primarily due to their ability to minimize side effects and enhance accumulation in tumour tissues [35,36]. Their potential has also been widely investigated in other therapeutic areas, including infectious diseases [37-39], cardiovascular disorders [40-43], metabolic disorders [44-47], neurological conditions [48-52] and rare diseases [53-56], among others.

Beyond the extensive preclinical research in nanomedicine development, many studies have progressed to clinical evaluation or are approaching this stage [48-50,57-61]. A search of the ClinicalTrials.gov database in December 2025 identified 815 registered studies involving nanoparticles, of which 135 had reported results and 252 were active, predominantly in Phase I and Phase II trials [62]. Complementing these clinical efforts, around one hundred nanomedicine formulations have achieved regulatory approval, providing concrete evidence of the translational potential and practical impact of nanotechnology in medicine [63,64].