Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: what should be the policy?

Abstract

Nanotechnology is the design and assembly of submicroscopic devices called nanoparticles, which are 1-100 nm in diameter. Nanomedicine is the application of nanotechnology for the diagnosis and treatment of human disease. Disease-specific receptors on the surface of cells provide useful targets for nanoparticles. Because nanoparticles can be engineered from components that (1) recognize disease at the cellular level, (2) are visible on imaging studies, and (3) deliver therapeutic compounds, nanotechnology is well suited for the diagnosis and treatment of a variety of diseases. Nanotechnology will enable earlier detection and treatment of diseases that are best treated in their initial stages, such as cancer. Advances in nanotechnology will also spur the discovery of new methods for delivery of therapeutic compounds, including genes and proteins, to diseased tissue. A myriad of nanostructured drugs with effective site-targeting can be developed by combining a diverse selection of targeting, diagnostic, and therapeutic components. Incorporating immune target specificity with nanostructures introduces a new type of treatment modality, nano-immunochemotherapy, for patients with cancer. In this review, we will discuss the development and potential applications of nanoscale platforms in medical diagnosis and treatment. To impact the care of patients with neurological diseases, advances in nanotechnology will require accelerated translation to the fields of brain mapping, CNS imaging, and nanoneurosurgery. Advances in nanoplatform, nano-imaging, and nano-drug delivery will drive the future development of nanomedicine, personalized medicine, and targeted therapy. We believe that the formation of a science, technology, medicine law-healthcare policy (STML) hub/center, which encourages collaboration among universities, medical centers, US government, industry, patient advocacy groups, charitable foundations, and philanthropists, could significantly facilitate such advancements and contribute to the translation of nanotechnology across medical disciplines.

Fig. 1

Demonstrates the size and scale of nanostructures relative to commonly known objects.

Fig. 2

(A) One pathway for nanostructures to reach target tissues is via the bloodstream. (B) Nanoshells can be used in imaging, as well as drug delivery. The core can be loaded with therapeutic agents that affect pathophysiological processes in the target tissue. (C) Quantum dots include a semiconductor nanocrystal core, which emits fluorescence in response to light. This schematic shows a quantum dot-based structure with an antibody coating. (D) This shows a nanoparticle functionalized with a targeting molecule interacting with a receptor at the target site. In this way, nanoparticles can deliver therapeutics and have localized versus systemic effects.

Fig. 3

Schematic view of Polycefin. (A) Schematic formula showing the composition of the nanoconjugate. The functional units (modules) have been chemically conjugated to the carboxyl groups of the PMLA platform. Percent values refer to total pendant carboxyl residues (100%). AON1 and AON2 are the Morpholino antisense oligonucleotides that target the mRNAs of laminin α4 and β1 chains, respectively. The drug-releasing unit is the disulfide group. Mouse anti-human TfR mAb targets tumor cells at their cell surface. PEG protects against enzymatic degradation. The fluorescent reporter group, AexaFuor 680, serves in vivo fluorescence imaging. L-Leucine ethylester moieties function in endosomal escape. The groups of 7.27% are the product of sulfhydryl blocking at the end of Polycefin synthesis and has no function. (B) A cartoon of Polycefin with the functional modules described in panel A.

Fig. 4

MWCNT (multi-walled carbon nanotube) internalization by BV2 microglia: 2.3 μg pMWCNTs-PKH was incubated with 1e6 BV2 cells for 48 h. Images were taken at 15, 24, and 48 h after pMWCNTs-PKH were added. Increasing numbers of pMWCNTs-PKH-positive cells were observed throughout this timecourse. (A) pMWCNTs-PKH-positive BV2 cells were imaged using an LSM 510 Meta confocal microscope at 48 h, mag. 400× (please also see the online video). (B) TEM microscopy was performed on cells incubated with MWCNTs after 2, 6, and 24 h. At 2 h single pMWCNTs were observed penetrating the cells surface, mag. 4400×. (C) A magnified image showing MWCNTs penetrating cell surface, mag. ×26,000.

Fig. 5

In vivo detection of MWCNT-PKH. MWCNT-PKH (5 μg) was injected intratumorally and assessed for internalization by immunohistochemistry 2 days later. MWCNTs are depicted in red (PKH), CD68+ cells (macrophage and microglia) are in green (FITC), and tumor nuclei are in blue (DAPI). MWCNT-PKH-positive CD68+ cells were noted throughout the tumor and tumor periphery (circles).

Fig. 6

This is a schematic of a third-generation (three shells, G3) dendrimer. Dendrimers can range from 1 to 10 nm, depending on the number of generations and properties of the terminal groups. The core can be composed of polymers and other nanoparticles and dendrimers. There is space within the dendrimer to load molecular cargo or other nanostructures. The terminal groups provide the surface functionalities and can include dyes, markers, and target directing groups.