Nanomedicine, the application of nanotechnology to medicine, has opened a new, previously unimaginable world in cancer diagnosis and therapy. Today new multifunctional nanoplatforms or smart nanomaterials (nanoparticle drones) can be constructed and endowed with image contrast enhancement capabilities for techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) (1, 2) and can contain therapeutic payloads programmed for targeted delivery to disease sites (3). The vision of combining diagnostics and therapeutics, now being referred to as theranostics, was considered futuristic only a few years ago but is now clearly achievable—the future is almost now!

A) Cartoon showing both intravenous and inhalation (INH) delivery of nanoparticle drones; (B) TEM image of lung tumor targeted with drones; (C) absorption spectra of drone technology uniquely customized for INH delivery to lung tumors.

Recognizing the potential impact of nanomedicine, the National Cancer Institute created the Alliance for Cancer Nanotechnology to leverage the potential of nanotechnology toward transforming the way cancer is diagnosed, treated, or prevented. Projects funded by this Alliance have led to significant research breakthroughs and have even entered successful clinical trials (4). Today, cancer nanomedicine now includes burgeoning research and development in nanoparticle-aided radiotherapy (NRT). A recent article (5) provides a robust review of NRT developments for over a decade in NRT with gold nanoparticles (GNPs), highlighting emerging approaches, challenges, and opportunities for further research toward clinical translation. Beyond GNP, other research has highlighted the use of alternative nanoparticle platforms like gadolinium nanoparticles (6, 7), hafnium nanoparticles (8), platinum-based chemotherapy drug platforms, and others with theranostic capability (9, 10).

In general, the key goal for NRT and cancer drug development efforts is the same, which is to optimize therapeutic efficacy/ratio. To this end, recent advances in the design of smart nanomaterials proffer tremendous potential toward realizing this goal. Such smart materials (11) are specifically designed to be sensitive to a specific stimulus, such as temperature, magnetic field, ultrasound intensity, light or radiation, and pH, and to then respond in active ways including radiosensitization or changing their structure for drug delivery, or other functions that have the potential to cogently enhance treatment outcomes.

Gold nanoparticles provide an excellent template for building such nanoparticle drones. They are biocompatible radiosensitizers (5), proffering relatively no toxicity. They can readily interact with photons by the photoelectric effect, to emit missile-like photoelectrons or Auger electrons in the micrometer range, to substantially boost RT damage to cancer cells. In the photoelectric effect, photons interact with the nanomaterials, with the probability of photoelectric interaction inversely proportional to the cube of the photon energy (5). Once the photoelectron is emitted, this creates a vacancy that may be filled by an electron from a higher energy level. The resulting release of energy could then also knockout Auger electrons. The Auger electrons are shorter range and with high linear energy transfer, so can lead to highly localized damage. Such highly localized damage to tumor cells can allow minimization of the primary radiotherapy dose and hence normal tissue toxicity. Nanoplatforms such as GNPs are also particularly attractive for building nanoparticle drones because they can provide CT and photoacoustic imaging contrast and are suitable for drug loading and attaching targeting moieties. Depending on surface functionalization, type of drug, and desired application, GNPs can be easily loaded with drugs or other molecules through either non-covalent interactions or covalent conjugation. Loading of drugs onto GNPs may improve their stability and biodistribution in biological media since the drugs are protected in the carrier. In short, multifunctional nanoparticle drones based on GNPs hold great promise in cancer nanomedicine.