Table 5.

Significant enhancements on the new biological applications of various NPs

NPs	Physicochemical properties	Animal model	Possible toxicity mechanism	Remarks	Ref.
Silica Nanorattle	Size: 125 nm with very narrow size distribution; detectable by doped fluorescent agents	Mice (liver cancer)	ROS production, however much less than non-porous silica due to less surface area	High drug loading capability; good conjugation potential with biomolecules; suitable contrast for in vivo detection using fluorescent agents; coating with polymeric materials (e.g. PEG) improves therapeutic efficacy, and reduces the toxicity of antitumor agents.	272, 273
Silicon nanocrystals	Overall size: 50 to 120 nm; formed by spherical aggregates of crystalline particles; good functionalization capability with organic molecules	Mice (different organs)	ROS production due to crystals and surface defects; membrane disruption	Better in vivo compatibility in comparison with QDs; suitable luminescent properties and long tumor accumulation times (> 40 h); targeted cancer imaging and sentinel lymph node mapping; oxidant injury and toxicity can be reduced by increasing size (e.g. aggregation) or changing charge	271, 274
Fullerenes	Size: 160 ±50 nm; zeta potential: −30 mV	Rat (lung tissue)	ROS production; oxidant injury to cellular membranes	Addition of ionic groups decreases systematic toxicity due to radical generation by the Fullerene surface (e.g. C60(OH)24)	275
Gold	Size 20 nm with very narrow size distribution; capability to be conjugated with variety of biochemical compounds	Athymic nude mice (tumor phantom model)	AU NPs can cause nephrotoxicity and eryptosis, or they can interact with DNA. Nevertheless, they are amongst the safest NPs reported to date.	Used as near-infrared fluorescence (NIRF) imaging probes by adding variable surface compositions of dye-labeled peptide substrates (for example Quasar 670); the probe enhances particle circulation time and image contrast in vivo. Cytotoxicity can be mitigated by modifying size or surface charge	276
Gold nanorods	Aspect ratio: ~ 3 (diameter of 15 nm and length of 50 nm)	Athymic nude mice (breast cancer tumors)	Nanorods are more internalized in the intracellular environment compared to spherical particles, as their high aspect ratio may retard initiation of phagocytosis. The slight toxicity of gold nanorods is due to toxic capping agents (e.g. ethyltrimethylammonium).	In comparison to spherical NPs, nanoroads have better capabilities as a probe for molecular imaging purposes; in order to reduce the toxicity of capping agents and to increase the blood circulation time of nanorods, biocompatible polymers (e.g. PEG) should be used as coating materials.	277
Semiconductor quantum dots (QDs)	Size: 80 nm	Mice (liver tissue), and lymphatic vessel	Release of toxic heavy metal ions (Cd and Se ions)	They usually belong to group II–VI elements of the periodic table, and have core-shell morphology. They are traceable by in vivo targeted fluorescence imaging. Their major short comings are the short circulation time and removal by reticuloendothelial system (RES) which causes reduction of tumor-specific signal, and the heavy metals used in their construction can cause long-term toxicity. Their fluorescence intensity in tumors can be enhanced significantly (more than 50%) by conjugation of targeting agents, e.g. epidermal growth factors. To reduce toxicity, the surface should be coated with biocompatible polymers or inorganic materials.	278, 279
Single-walled carbon nanohorns	Diameter 2–5 nm, and length 40–50 nm. Single-walled carbon nanohorns (diameter 100 nm)	Mice (liver and spleen tissues)	Production of ROS (metal impurities) followed by inflammatory effects	Determination of their biodistribution is inconvenient; however, in order to overcome this problem, Gd2O3NPs can be embedded within single-walled carbon nanohorns (i.e. Gd exhibits a high electron scattering ability). For drug delivery purposes, drugs can be loaded and stored inside open oxidant holes.	280, 281
Calcium phosphate	Size: <50 nm (10–50 nm)	Breast cancer	Possible ROS production due to crystal defects if crystalline, or surface defects if amorphous	Good biocompatibility; indocyanine green (ICG) molecules can be embedded as a near-infrared (NIR) emitting fluorophore to enhance in vivo contrast. The ICG-encapsulating NPs have noticeably higher fluorescence and stability in vivo compared to the free fluorophore. Suitable for deep tissue imaging. In order to enhance the circulation time, the surface of the NPs should be coated or functionalized (e.g. PEG or carboxylate).	282
Silver	Size: 5–46 nm	Zebrafish embryos	Cell suffocation due to inhibitory effect of silver ions on respiratory enzymes; generation of ROS and membrane disruption	Ag NPs have high quantum yields. Ag NPs can be used to probe inside embryos. Optical properties were fully dependent on the size and shape of Ag NPs. There was no trace of particle aggregation or photo decomposition, thus continuous imaging for long periods of time is possible.	283
SiO2 and Al2O3	Sizes: 19 and 12 nm for SiO2 and Al2O3, respectively; shape: spherical	Zebrafish embryos	ROS production	No physiological and morphological defects. Usually coating can reduce toxicity
Pt	Size: 13 nm; shape: spherical	Zebrafish embryos	ROS production	Inhibitory effects on cardiac rate. Pericardial edema, low heart beat and mortality were observed.
ZnO	Size: 10 nm; shape: Spherical	Zebrafish embryos	ROS production, release of toxic cations with damage to cell membranes	The most prominent lethalities were morphological abnormalities, or interference with embryo hatching, unhatched embryos, and disintegrated embryos.