Infrared-Transparent Gold Nanoparticles Converted by Tumors to Infrared Absorbers Cure Tumors in Mice by Photothermal Therapy

Abstract

Gold nanoparticles (AuNPs) absorb light and can be used to heat and ablate tumors. The “tissue window” at ∼800 nm (near infrared, NIR) is optimal for best tissue penetration of light. Previously, large, 50–150 nm, gold nanoshells and nanorods that absorb well in the NIR have been used. Small AuNPs that may penetrate tumors better unfortunately barely absorb at 800 nm. We show that small AuNPs conjugated to anti-tumor antibodies are taken up by tumor cells that catalytically aggregate them (by enzyme degradation of antibodies and pH effects), shifting their absorption into the NIR region, thus amplifying their photonic absorption. The AuNPs are NIR transparent until they accumulate in tumor cells, thus reducing background heating in blood and non-targeted cells, increasing specificity, in contrast to constructs that are always NIR-absorptive. Treatment of human squamous cell carcinoma A431 which overexpresses epidermal growth factor receptor (EGFr) in subcutaneous murine xenografts with anti-EGFr antibodies conjugated to 15 nm AuNPs and NIR resulted in complete tumor ablation in most cases with virtually no normal tissue damage. The use of targeted small AuNPs therefore provides a potent new method of selective NIR tumor therapy.

Cancer therapy using nanoformulated substances: scientific, regulatory and financial aspects

“…following treatment and to a one year survival rate of 50-86%, higher than that of 0-20% observed for a treatment with radiation alone, (80)(81)(82). NIR heating of AuNPs in mice with squamous carcinoma showed tumour disappearance after three days, (83). It was also demonstrated that NIR absorption of light is 100 000 higher with AuNPs than with standard fluorophores, (83).…”

“…NIR heating of AuNPs in mice with squamous carcinoma showed tumour disappearance after three days, (83). It was also demonstrated that NIR absorption of light is 100 000 higher with AuNPs than with standard fluorophores, (83).…”

Gold nanoparticle hyperthermia reduces radiotherapy dose

“…Since solid spherical AuNPs do not absorb significantly at 800 nm, another approach is to have tumor cells take them up and aggregate them in endosomes and lysosomes 20–22 . When AuNPs aggregate, their absorption spectrum red-shifts 23, 24 , which can be into the NIR.…”

“…When AuNPs aggregate, their absorption spectrum red-shifts 23, 24 , which can be into the NIR. The advantages of using small AuNPs (e.g., 1–20 nm), compared to nanoshells (~130 nm) and nanorods (~50 nm) might be: a) better penetration into tumors 22, 25–28 , and b) lower background absorption in non tumor cells and blood that do not aggregate the AuNPs (i.e., the small AuNPs ideally only aggregate and become NIR absorptive in the tumor while background amounts in normal tissue are unaggregated and NIR transparent and do not contribute to heating compared to NPs that are preformed to absorb NIR wherever they are).…”

Apolipoprotein E3-mediated cellular uptake of reconstituted high-density lipoprotein bearing core 3, 10, or 17 nm hydrophobic gold nanoparticles

“…Other researchers demonstrated that formulations of AuNPs functionalized with Erbitux (an anti-epidermal growth factor receptor antibody) lead to targeted endosome and lysosome delivery. 54 The present study relies on apoE3-mediated lipoprotein uptake mechanism adopted by cells to process the rHDL-AuNP.…”