On-demand intracellular amplification of chemoradiation with cancer-specific plasmonic nanobubbles

Abstract

Chemoradiation-resistant cancers limit treatment efficacy and safety. We show here the cancer cell–specific, on-demand intracellular amplification of chemotherapy and chemoradiation therapy via gold nanoparticle– and laser pulse–induced mechanical intracellular impact. Cancer aggressiveness promotes the clustering of drug nanocarriers and gold nanoparticles in cancer cells. This cluster, upon exposure to a laser pulse, generates a plasmonic nanobubble, the mechanical explosion that destroys the host cancer cell or ejects the drug into its cytoplasm by disrupting the liposome and endosome. The same cluster locally amplifies external X-rays. Intracellular synergy of the mechanical impact of plasmonic nanobubble, ejected drug and amplified X-rays improves the efficacy of standard chemoradiation in resistant and aggressive head and neck cancer by 100-fold in vitro and 17-fold in vivo, reduces the effective entry doses of drugs and X-rays to 2–6% of their clinical doses and efficiently spares normal cells. The developed quadrapeutics technology combines four clinically validated components and transforms a standard macrotherapy into an intracellular on-demand theranostic microtreatment with radically amplified therapeutic efficacy and specificity.

Laser-assisted photoporation: fundamentals, technological advances and applications

“…Anti-cancer drugs have been delivered by photoporation into cancer cells for an enhanced chemotherapeutic effect [160]. The same group showed that direct delivery of the anti-cancer drug into the cell's cytoplasm by photoporation substantially enhanced the effect of chemoradiation in vivo [161]. Also GO NPs were used to deliver a photosensitizer into cells for enhanced photodynamic therapy efficacy against the cancer cells in vitro [142].…”

“…Recently, the Lapotko group applied for the first time AuNP-sensitized photoporation of chemotherapeutics to in vivo cancer treatment. [161]. The same group recently showed in vivo elimination of residual head and neck cancer cells by tumor targeting gold colloids [162].…”

Characterization of periodic cavitation in optical tweezers

“…These transient nanobubbles have shown great potential for medical treatments [15]. Optical tweezers or highly focused continuous (CW) lasers have been used to create micron sized cavitation bubbles in liquids that are transparent to the laser wavelength [16,17].…”

Towards graphene plasmon-based free-electron infrared to X-ray sources

“…The emission intensity is presented as a function of the polar angle of the outgoing radiation (horizontal) and its energy (vertical). The GP has a temporal frequency of 2x10 14 Hz (λair = 1.5 μm), in a graphene sheet that is electrostatically gated, or chemically doped, to have a spatial confinement factor (ratio of free space wavelength to GP wavelength) of n = 180. Fig.…”

“…1, the GP has a temporal frequency of 2x10 14 Hz (λair = 1.5 μm), in a graphene sheet that is electrostatically gated, or chemically doped, to have a carrier density of ns = 3.2x10 13 cm -2 (Fermi level Ef = 0.66 eV). This gives a GP spatial period of 8.33 nm [26], corresponding to a spatial confinement factor (ratio of free space wavelength to GP wavelength) of n = 180.…”