text: The failure of clinical translation of nanoparticles-mediated PTT is mainly ascribed to concerns about their persistence in the body. Indeed, the optical response of anisotropic nanomaterials can be tuned in the NIR region by increasing their size to up to 150 nm. On the other hand, body excretion of non-biodegradable noble metals nanomaterials above 10 nm occurs through the hepatobiliary route in a slow and inefficient manner. A common approach to avoid metal persistence is to reduce the nanoparticles size below the threshold for renal clearance, i.e. ultrasmall nanoparticles (USNPs), meanwhile the maximum light-to-heat transduction is for < 5 nm nanoparticles. On the other hand, the surface plasmon of excretable gold USNPs is in the UV/visible region (far from the first biological windows), severely limiting their potential application in PTT.
  Excretion of metals has been combined with NIR-triggered PTT by employing ultrasmall-in-nano architectures composed by metal USNPs embedded in biodegradable silica nanocapsules. tNAs are the first reported NIR-absorbing plasmonic ultrasmall-in-nano platforms that jointly combine: i) photothermal conversion efficacy suitable for hyperthermia, ii) multiple photothermal sequences and iii) renal excretion of the building blocks after the therapeutic action. Nowadays, tNAs therapeutic effect has been assessed on valuable 3D models of human pancreatic adenocarcinoma.