Future of Cancer Therapy: Advanced Functional Nanomaterials to Image and Deliver Drugs into Tumors

Title: Controlled Assembly of Biodegradable Plasmonic Nanoclusters for Near-Infrared Imaging and Therapeutic Applications
Authors: Jasmine M. Tam, Justina O. Tam, Avinash Murthy, Davis R. Ingram, Li Leo Ma, Kort Travis, Keith P. Johnston, and Konstantin V. Sokolov
Journal: ACS Nano

Gold has been historically a great commodity for a very long time that has been used in general exchange as a currency. Today, while it is still a very popular safe haven for wealth, it has attracted a special attention among scientists for high-tech applications, including cancer therapy.

In this paper, a new generation of biodegradable contrasting/drug-delivery agents has been introduced by Johnston group, where clusters of gold nanoparticles (Au NPs) have been assembled by controlling the depletion forces (depletion force is an attractive force that arises between macromolecules that are suspended in a dilute solution of depletants, which are smaller solutes that are preferentially excluded from the vicinity of these macromolecules) of a degradable copolymer of polylactic acid and polyethylene glycol.
Gold NPs, as an inert and non-toxic material with great surface plasmon resonance (Surface plasmon resonance, SPR, is the resonant oscillation of conduction electrons stimulated by incident light) properties, have a great potential to be used as contrasting/drug-delivery agents for cancer therapy. However, unfortunately almost all of the near-infrared-active Au NPs are bigger than 5 nm in size and therefore, they aren’t renally cleared and they would accumulate inside the liver. Obtaining FDA approvals for such contrasting/drug-delivery agents are very unlikely considering the potential side effects of the accumulation of these metallic NPs inside the body.
In this paper, sub-5 nm Au NPs were assembled together into ~50 nm nanocluster with very high near-infrared (NIR) adsorption. These clusters can be used as effective contrasting agents for biomedical imaging as well as drug delivery agents by loading drugs on these clusters. Interestingly, these nanoclusters can degrade inside the cellular environment (after the imaging and curing process) in less than 48 hrs and go back from 50 nm nanoclusters into sub-5nm individual NPs that can get cleared by the kidneys. Therefore, the removal of these NPs greatly reduces the long-term concerns about the possible health issues that the accumulation of these NPs inside the body may cause.
By controlling the interparticle interactions, including van der Waals, electrostatic, electrosteric and depletion forces, the Au NPs was assembled into dense ~50nm nanoclusters capped with a thin polymeric shell which enhance the stability and transportability of the nanoclusters in the body. Upon diffusion of these nanoclusters into cancerous cells, the lactic acid segments of polymeric shell start to degrade and hydrolyze at pH around 5. Once the polymeric shell is degraded, the nanoclusters disassemble into individual 5nm NPs which have very short circulation time inside the body.
These new class of contrasting agents seem to provide a great opportunity to effectively image tumor cells inside the body without the risk of long-term side effects of the accumulation of these NPs. Based on the presented results, the ability to achieve a high loading of nanoclusters into cells may provide an opportunity for drug delivery into tumor cells as well.

Schematic representation of the assembly of sub-5nm AuNPs into nanoclusters and dissociation of these clusters back into individual primary nanoparticles in cellular enviroment

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