MRI is used as a non-invasive imaging method that is especially appropriate for soft tissue based on the property of nuclear magnetic resonance (Harisinghani et al.,2003). After excitation by a selective radio-frequency pulse, the active nuclei will be relaxed rapidly and then return to their initial state in MRI procedure. This relaxation procedure is divided into two parts, i.e., longitudinal relaxation (T1) and transverse relaxation (T2). Both can generate magnetic resonance images for discriminating different tissues. Although MRI is a relatively expensive and time-consuming tool, it has enormous advantages such as high spatial resolution in three-dimensions, high contrast of soft tissues, facile extractions of physiological, anatomical and molecular information (Veiseh et al.,2010). Gadolinium (Gd³⁺) chelates that behave as paramagnetic complexes are usually used in MRI contrast agents, e.g., Gd-DTPA is widely used in recent years (Tamada et al.,2009). However, repeated injections are needed with high chelates dosage to elongate blood circulation time, which, nevertheless, inevitably brought about some inaccuracies due to the false positive contrast enhancement (Huang et al.,2012).

MRI contrast agents that refer to nanomaterials with uniform size, enhanced relaxation properties and biocompatibility attract scientists’ eyes (Jun et al., 2005; Park et al.,2004). Food and Drug Administration (FDA) approved super paramagnetic iron oxide (SPIO) as a nanoparticle contrast agent in clinical trials (Thorek et al.,2006). SPIO is now widely used in T₂ contrast agents. Many nanoparticles such as NiFe₂O₄, MnFeO₄ and CoFe₂O₄ have also been proved for T₂ contrast agents (Khemtong et al.,2011). Nanoparticle Gd-based contrast agents such as Gd₂O₃, GdPO₄ and GdF₃ can enhance the signal of T1-weighted MRI (Figure 2) (Jun et al., 2005; Jung et al., 2009; Park et al., 2004; Yin et al., 2012; Zhang et al., 2011). Intriguingly, ultrasmall-sized iron oxide nanoparticles (ESIONs) with sizes less than 4 nm have been proved as good candidates for T₁-weighted imaging (Kim et al.,2011). However, these novel nanoparticles are still in the stage of preliminary animal studies in vivo for MRI. There is a long way to before entering human before addressing their biocompatibility and pharmacokinetics concerns (Huang et al.,2012).

PET is a nuclear medicine imaging method, and it can provide quantitative and sensitive readout of an administered radiotracer in order to evaluate the targeting pharmacokinetics and efficiency objective to tissues or organs (Ametamey et al.,2008; Shokeen & Anderson, 2009). Gold nanoparticles are mostly used nanomaterials in PET. Radioiodine-124-labelled tannic acid gold core–shell nanoparticles are used in PET for dendritic cell labelling and tracking, because it shares high radiosensitivity, desirable labelling efficiency and excellent chemical stability. The novel nanoparticles are also good at monitoring cell biological functions such as proliferation and phenotype marker expression (Lee et al.,2017). Results showed that ¹²⁴I-labelled gold nanostar probes could be used for brain tumors in PET. ¹²⁴I-labelled gold nanostar probes can reach sub-mm intracranial for brain tumour detection (Liu et al.,2019). Radioactive [⁶⁴ Cu]CuS nanoparticles is also used for PET. Especially when they were conjugated to RGDfK peptides by PEG linkers, they are equipped with a robust ability to target tumor and allowed to be uptaken by tumors. Thus, they can be used to enhance PET for realizing theranostic application (Cui et al.,2018). Very recently, pharmacokinetically-optimized ⁶⁴Cu-labelled polyglucose nanoparticles (Macrin) were developed for quantitative PET imaging of macrophages (Kim et al.,2018).

Besides above gold and copper sulfide nanoparticles, there are many other nanoparticles that can be used in PET, e.g., ¹¹C, ¹³N, ¹⁵O and ¹⁸F are also radioactive contrast agents for PET. Typically, ¹⁸F-Macroflor modified polyglucose nanoparticles have a relatively high avidity for macrophages. They are small and excreted renally, thus increasing the PET signal (Keliher et al.,2017).

Based on photoacoustic effect, photoacoustic imaging is a promising branch of ultrasound or optical modalities. Photoacoustic effect is a part of non-ionizing laser pulse which is absorbed by tissues and then converted into heat. Due to transient thermoelastic expansion, there are wideband ultrasonic waves. So photoacoustic imaging is a hybrid biomedical imaging modality. Ultrasonic images can be made by the generated ultrasonic waves in photoacousic imaging (Zhang et al.,2006). It is an excellent method and outperforms optical imaging in visualizing both biological structures and functions due to its penetration depth, prominent contrast and spatial resolution (Figure 3) (Wang et al.,2003; Yao & Wang, 2000).

Some exogenous agents can improve the photoacoustic imaging. Generally, the most important abilities of PAI contrast agents is to convert the light into heat and produce ultrasound waves. Almost all photothermal materials such as carbon, silver, gold, etc., have this ability. After reconstructing, these materials can distinguish cancer tissues from healthy tissues. Gold-based nanomaterials are promising PAI contrast agents because of their localized surface plasmon resonance effect and can convert light into heat efficiently. The surface of gold is inert, determining the biocompatibility in vivo research. Li et al. constructed PEG-HAuNS with both ultrasound and optical properties as contrast agents. This nanomaterial has no acute toxicity in many organs. Its properties in spatial resolution are admirable and good for photoacoustic imaging (Lu et al.,2010). The silver is also known as high surface plasmon resonance. Due to stronger light absorption, silver is theoretically preferable than gold in constructing photoacoustic contrast agent. However, they are more cytotoxic in vivo. So, silver-based nanomaterials demand more studies to address their biocompatibility. Carbon-based materials have high resolution and allow imaging of deep areas, holding high potential in clinical translation. Gambhir et al. constructed single-walled carbon nanotubes with a cyclic Arg-Gly-Asp (RGD) peptide as agents in photoacoustic imaging (De la Zerda et al., 2008).

Chemotherapy is always used in treating metastatic types of cancers (Wang et al.,2017). Doxorubicin (DOX) and paclitaxel are popular chemotherapeutic drugs which can be used in breast cancer. Chemotherapy regimens such as tamoxifen, trastuzumab, docetaxel and cisplatin are also used in chemotherapy (Siddique & Chow, 2020). Nanoparticle-based carriers conjugating with these chemotherapeutic drugs are often used in targeted delivery. For example, nanoparticles based on polymer, metal, mesoporous silica, protein and carbon, are used in chemotherapy (Liyanage et al.,2019). Different kinds of proteins and peptides are combined with nanoparticles to help improve selectivity of chemotherapeutice drugs.

Gold nanoparticles have distinctive characteristics such as multifunctionalities, high stability, high surface plasmon resonance and large surface area-to-volume ratio. Importantly, Au nanoparticles exhibit additional benefits such as nonimmunogenic nature, nontoxic, high permeability and retention effect. Thus Au nanoparticles carrier enabled penetration and accumulation of chemotherapeutic drugs at tumor areas. Typically, EpCAM-RPAnN and DOX-BLM-PEG-Au NPs are Au nanoparticle-based drug delivery systems that can be applied into chemotherapy (Singh et al.,2018). As well, organic nanoparticles are also good choice for drug delivery in chemotherapy since they can increase tumor accumulation of drugs and prolong their circulation half-time. Briefly, nanoparticles can behave as theranostic platform and deliver many drugs to targeted area (Meng et al.,2017).

Radiotherapy is also primarily used for various nonmetastatic cancers (Wang et al.,2017). Nanovectorized radiotherapy based on nanoparticles for radionuclides delivery can serve as a reservoir to supply radionuclides to cancer cells specifically. This novel method stimulates immune response and cell killing by using peculiar biomaterials (Vanpouille-Box et al.,2011). Many studies have found that nanomaterials can significantly increase the efficiency of radiotherapy.

Nanomaterials have many advantages, such as high toleration, low toxicity and long circulation time. Some of nanomaterials can even act as radioprotectors when exposed to radioactive substances (Nambiar & Yeow, 2012). Colon et al. indicated that cerium oxide (CeO₂) nanoparticles protected the cells from radiation-induced damages both in vivo and in vitro (Colon et al.,2009; Heckert et al.,2008). Schweitzer et al. synthesized melanin-covered nanoparticles and found that they could provide a new way to protect bone marrow from ionizing radiation (Schweitzer et al.,2010). Brown et al. found that fullerene compound DF-1 could serve as a radiation protector. As a radiation protector, DF-1 has modest activity in vivo and could reduce DNA double strand (Brown et al.,2010).

Photothermal therapy (PTT) is a cancer treatment method based on hyperthermia. It can destroy tumor cells and simultaneously avoid to heat normal areas. Nanomaterials such as nanocages, nanoshells, nanostars and nanocages are mostly used as photothermal transducers. Au nanoparticles and near-infrared (NIR) can be used to selectively and precisely heat tumors (Hirschberg & Madsen, 2017). With rich amine and thiol groups, gold nanoparticles can be used as drug products to realize targeted delivery when combining with antibodies. Colloidal gold always localizes plasmon surface resonance, thus absorbing light with specific wavelengths. In this regard, it is helpful in hyperthermic cancer treatment. As the shape or size of particles change, the localized plasmon surface resonance of gold nanoparticles can also be tuned. Accordingly, the properties of photothermal and photoacoustic can be altered (Vines et al.,2019).

PTT suffers from one major problem that is the heterogeneous heat distribution in tumors, which thus leaves some tumor area untreated and causes incomplete ablation. Silica-coated gold nanoshells are proposed to deliver fractionated PTT (Simon et al.,2019). PTT’s main mediators are gold nanoshells due to their high photothermal conversion efficient, excellent biocompatibility, facile gold thiol bioconjugation chemistry and high tumor penetration. The temperature at the tumor is raised aboveb42°C in order to destroy cancer cells. Therefore, a light-absorbing material should improve the energy selectivity for heat transduction. Although gold is mostly used in PTT, magnetic nanoparticles are good alternatives (Siddique & Chow, 2020). Magnetic nanoparticles can combine with other materials or serve as photothermal agents themselves. They can penetrate into tumor area magnetically and their molar absorption coefficient in NIR is low when used alone. Magnetic nanoparticles can also be used in drug delivery, which enables the marriage of PTT and chemotherapy (Estelrich & Busquets, 2018).

Photodynamic therapy (PDT) is a combination of light and photosensitizers. When exposed to light, photosensitizer is able to convert light into reactive oxygen species (ROS) and kill tumor cells through necrosis or apoptosis (Celli et al.,2010). PDT can exert the potent effects to destroy cells and vasculature of the tumor. Because of the light-absorbing photosensitizer’s special and designated localization, the subsequent biological responses can happen in those designated areas (Brown et al.,2004). PDT has potential in clinical cancer treatment with reduced side effects.

Imaging is added as a direct guidance for localizing photosensitizers. Rai et al. integrated PDT with imaging using the NIR-light absorbed photosensitive molecules (Figure 4)(Rai et al.,2021). So far, a variety of nanomaterials have been developed to behave as carriers to enhance PDT such as semiconductor quantum dots, silica nanoparticles, nanocapsules, gold-based nanomaterials and some metal-based nanomaterials (Gary-Bobo et al.,2011; Son et al.,2011). Gold-based nanomaterials have excellent characterisitics for both PDT and optical imaging. Choi et al. proposed a nanomedicine platform consisting of photosensitizer AlPcS4 and gold nanorods (Jang et al.,2011). Based on this nanoplatform, tumor areas can be discerned by NIR fluorescence imaging, and then dual PDT and PTT was carried out effectively ablate them (Figure 5) (Jang et al.,2011). Wang et al. used photosensitizer Chlorine6 (Ce6) to conjugate with NIR light-excited upconversion nanoparticles (UCNPs) for tumor therapy (Wang et al.,2011).