Challenges to effective cancer nanotheranostics

Abstract

Advances in nanotechnology for oncology will arise from an increased understanding of the interaction between nanomaterials and biological systems; refinement of multifunctional nanocomposites for applications such as simultaneous imaging and therapy (theranostics); and harnessing of the unique physicochemical properties arising from nanoscale effects which distinguish them from small-molecular-weight molecules in the detection and destruction of cancer cells with high selectivity and efficiency. The major challenges in successful clinical translation of tumor specific nanoparticle delivery include overcoming various biological barriers and demonstrating enhanced therapeutic efficacy over the current standard of care in the clinic. For many nanoparticle mediated theranostic applications, image guidance can play a crucial role not only in exploiting the cancer specific imaging capabilities of these novel particles, but in planning, targeting, monitoring and verifying treatment delivery, thus enhancing the safety and efficacy of these emerging procedures.

Fig. 1

Selective binding of anti-EGFR-conjugated HAuNS to A431 cells. A431 cells were seeded onto a 96-well plate and incubated with C225-HAuNS (7.3 × 10¹⁰ particles/mL), IgG-HAuNS (7.3 × 10¹⁰ particles/mL), or C225 (500 μg/mL) plus C225-HAuNS for 30 min at 37°C. Only cells incubated with C225-HAuNS had a strong light-scattering signal. Cells were stained with DAPI for visualization of cell nuclei (blue). Light-scattering images of nanoshells were pseudocolored green. Original magnification, ×630. Reproduced with permission [5].

Fig. 2

Biodistribution of ¹¹¹In-labeled DTPA-C225-HAuNS and DTPA-IgG-HAuNS. The mean uptake of ¹¹¹In-DTPA-C225-HAuNS in the liver (± standard deviation [SD]) was significantly higher than that of ¹¹¹In-DTPA-IgG-HAuNS (p=0.001). Also, the mean tumor uptake of ¹¹¹In-DTPA-C225-HAuNS (± SD) was higher than that of ¹¹¹In-DTPA-IgG-HAuNS, but the difference was not statistically significant (p=0.08; n=4/group of mice). Reproduced with permission [5].

Fig. 3

Intratumoral distribution of hollow gold nanospheres (HAuNS). (A) Dark-field microscopic images of the perivascular areas in slices of A431 tumors in mice injected with C225-HAuNS and IgG-HAuNS. HAuNS were pseudocolored green. Cell nuclei were stained with DAPI (blue). (B) Graph of the mean particle counts per viewing field (± SD) under the dark-field microscope (magnification 200×; n=5/group of mice; *p<0.01) compared with C225-HAuNS. Reproduced with permission [5].