Cancer nanomedicine: from targeted delivery to combination therapy

Abstract

The advent of nanomedicine marks an unparalleled opportunity to advance the treatment of various diseases, including cancer. The unique properties of nanoparticles (NPs), such as large surface-to-volume ratio, small size, the ability to encapsulate various drugs, and tunable surface chemistry, give them many advantages over their bulk counterparts. This includes multivalent surface modification with targeting ligands, efficient navigation of the complex in vivo environment, increased intracellular trafficking, and sustained release of drug payload. These advantages make NPs a mode of treatment potentially superior to conventional cancer therapies. This review highlights the most recent developments in cancer treatment using NPs as drug delivery vehicles, including promising opportunities in targeted and combination therapy.

Keywords: cancer; combination therapy; nanomedicine; targeted delivery.

Figure 1. Schematic of a system in which nanoparticle (NP) precursors enter a multi-inlet mixer at different ratios to self-assemble a library of NPs

Programmable mixing of polymer precursors allows for synthesis of NPs with a wide range of sizes, surface chemistry, charge, and targeting agent densities. Adapted with permission from [16].

Figure 2. Red blood cell membrane–coated PLGA NPs

Cellular membranes provide a robust natural functionality to the particle. In comparative studies with PEG-coated NPs, RBC membrane–coated NPs exhibited a 39.6-hour half-life compared with 15.8 hours for PEG NPs. Adapted with permission from [34].

Figure 3. Passive targeting, active targeting, and combinatorial delivery

In passive targeting (left), the NPs passively extravasate though the leaky vasculature via the EPR effect and preferentially accumulate in tumors. In active targeting (middle), targeting ligands on the surface of the NP trigger receptor-mediated endocytosis for enhanced cellular uptake. In combinatorial delivery (right), two or more therapeutic agents inhibit different or identical disease pathways for a synergistic effect.

Figure 4

Antibody functionalization and visualization. (a) Antibodies conjugated to the NP surface through “click” chemistry. (b) Cells that express the complementary antigen are blue and show Ab-facilitated binding of targeted NPs. Cells that do not express the complementary antigen are green with no NP binding. (c) Fluorescence microscopy images of huA33 mAbAzfunctionalized nanocapsules with (i) the antibody labeled with AF647 (red), or (ii) antibody labeled with AF488 (green), (iii) brightfield, and (iv) overlay images. Adapted with permission from [61].