Intravascularly injectable nanovectors are a class of nanotechnological devices used in cancer. Their envisioned use is for the in vivo, non-invasive visualization of molecular markers of early stages of disease; the targeted delivery of therapeutic agents, with a concurrent, substantial reduction of deleterious side effects; and the interception and containment of lesions before they reach the lethal or even the malignant phenotype, with minimal or no concurrent loss of quality of life.
Liposomes are the simplest form of a nanovector that use the overexpression of fenestrations in cancer neovasculature to increase drug concentration at tumour sites. They are only the first in an ever-growing number of nanovectors under development for novel, more efficacious drug-delivery modalities. Liposome-encapsulated formulations of doxorubicin were approved 10 years ago for the treatment of Kaposi’s sarcoma, and are now used to treat breast cancer and refractory ovarian cancer.
Nanovectors in general have at least a tripartite constitution, featuring a core constituent material, a therapeutic and/or imaging payload, and biological surface modifiers, which enhance the biodistribution and tumour targeting of the nanoparticle dispersion (as seen in the figure). The figure shows the final stage of the intravenous journey with the arrival of a nanocarrier which is about 100 times smaller than a strand of hair and its payload of anti-cancer medication.
A major clinical advantage sought by the use of nanovectors over simple immunotargeted drugs is the specific delivery of large amounts of therapeutic or imaging agents per targeting biorecognition event. Targeting methods that have been investigated range from covalently linked antibodies to mechanisms based on the size and physical properties of the nanovector. Nanovectors are designed to reduce the clearance time of small peptide drugs, provide protection of active agents from enzymatic or environmental degradation, and avoid obstacles such as protective exclusion by the blood–brain barrier or the vascular endothelium or osmotic pressure states in cancer lesions to the targeting of the active moiety. The exclusion or the augmented osmotic pressure can result in outward convection of the therapeutic moiety and nanoparticle sequestration by the Reticulo-Endothelial System (RES).
The nanovectors act as carriers for the therapeutic and imaging payloads, or their constituent materials might also possess image-enhancement properties, such as in the case for iron oxide for MRI, and semiconductor nanocrystals or quantum dots for optical imaging.
Many polymer-based vectors have been investigated and seem most promising for clinical translation. For instance, dendrimers are self-assembling synthetic polymers with exquisitely tunable nanoscale dimensions, which were recently used for the MRI of the lymphatic drainage in a mouse model of breast cancer. This indicates that dendimer-based contrast agents might be
used to non-invasively detect cancer cells in the lymph nodes in patients, to provide early signals of disease, or information about patterns
of metastatic spread.
Silicon and silica are emerging as interesting candidate materials for injectable nanovectors. Porosified silicon is biodegradable, with kinetics that are much more rapid (minutes to hours) than those of biodegradable polymers (weeks to months), and therefore release drugs with previously unattainable
time profiles.
Metal-based nanovectors include nanoshells, which comprise a gold layer over a silica core. The thickness of the gold layer can be precisely tuned, so that the nanoshell can be selectively activated through tissue irradiation with near-infrared light to perform localized therapeutic thermal ablation.
Thus the nanovectors can be used as highly selective, externally activated therapeutic agents. It is estimated that several thousand different nanovector types have been reported in the literature. Just a minute fraction of their potential uses against cancer have been explored, yet these offer technological foundations for meeting the fundamental cancer nanotechnology challenges.
