Active targeting of nanoparticles to tumours can be achieved by conjugation with specific antibodies. Specific active targeting of the HER2 receptor is demonstrated in vitro and in vivo with a subcutaneous MCF-7 breast cancer mouse model with trastuzumab-functionalized gold nanoparticles. The number of attached antibodies per nanoparticle was precisely controlled in a way that each nanoparticle was conjugated with either exactly one or exactly two antibodies. As expected, in vitro we found a moderate increase in targeting efficiency of nanoparticles with two instead of just one antibody attached per nanoparticle. However, the in vivo data demonstrate that best effect is obtained for nanoparticles with only exactly one antibody. There is indication that this is based on a size-related effect. These results highlight the importance of precisely controlling the ligand density on the nanoparticle surface for optimizing active targeting, and that less antibodies can exhibit more effect.

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Understanding the behavior of multifunctional colloidal nanoparticles capable of biomolecular targeting remains a fascinating challenge in materials science with dramatic implications in view of a possible clinical translation. In several circumstances, assumptions on structure-activity relationships have failed in determining the expected responses of these complex systems in a biological environment. The present Review depicts the most recent advances about colloidal nanoparticles designed for use as tools for cellular nanobiotechnology, in particular, for the preferential transport through different target compartments, including cell membrane, cytoplasm, mitochondria, and nucleus. Besides the conventional entry mechanisms based on crossing the cellular membrane, an insight into modern physical approaches to quantitatively deliver nanomaterials inside cells, such as microinjection and electro-poration, is provided. Recent hypotheses on how the nanoparticle structure and functionalization may affect the interactions at the nano-bio interface, which in turn mediate the nanoparticle internalization routes, are highlighted. In addition, some hurdles when this small interface faces the physiological environment and how this phenomenon can turn into different unexpected responses, are discussed. Finally, possible future developments oriented to synergistically tailor biological and chemical properties of nanoconjugates to improve the control over nanoparticle transport, which could open new scenarios in the field of nanomedicine, are addressed.

We present a facile, one-pot procedure for the organic-to-water phase transfer and biofunctionalization of semiconductor nanocrystals (quantum dots, or QDs) which employs a synthetic functional copolymer, namely poly(DMA-NAS-MAPS), consisting of three components: a surface interacting monomer, N,N-dimethylacrylamide (DMA), a chemically reactive monomer, N-acryloyloxysuccinimide (NAS), and a silane monomer, [3-(methacryloyloxy)-propyl]-trimethoxysilane (MAPS). The nanocrystals were transferred to water by exploiting the amphiphilic character of the copolymer backbone. Hydrolyzed MAPS units contributed to improve the solubility of QDs in water, whereas NAS exhibited reactivity toward biomolecules. A solution of streptavidin in phosphate buffer exhibited good dispersion ability leading to a clear and transparent colloidal suspension, indicative of good QD dispersion during phase transfer and purification. Unlike most of the published methods, the proposed functionalization approach does not require coupling agents and multistep reactions.