Singlet oxygen-generating upconversion nanoplatforms: from photophysical design and dosimetry to biological interactions and nanosafety

Upconversion nanoparticles absorb near-infrared light and re-emit it at shorter wavelengths, which allows conventional photosensitizers to be activated deep inside tissue, beyond the reach of their own absorption bands. Such systems have been built from many combinations of host lattice, dopant, shell architecture, surface coating and photosensitizer attachment chemistry, and applied to tumors, to drug-resistant bacteria and to biofilms. This review draws on 108 primary studies and asks why platforms that are individually well characterized remain so difficult to rank against one another. The difficulty is metrological rather than synthetic. As a first-order approximation, overall 1O₂ generation by the assembled system depends on the upconversion quantum yield, the donor–acceptor energy-transfer efficiency, and the 1O₂ quantum yield of the photosensitizer within the construct. These terms are not strictly independent, because photosensitizer loading, aggregation, coupling, and the surrounding medium can modify the efficiency of each step. The first two terms are reported unevenly across the corpus and the third almost never, since a singlet oxygen quantum yield measured on the assembled construct appears in fewer than one study in ten. Light dosimetry follows the same pattern, because irradiance and exposure time are given in most studies while radiant exposure calculated by the authors appears in only a small minority, and the reported irradiances span four orders of magnitude, with several exceeding the skin-exposure benchmarks cited in the respective studies. Measurements also carry method-specific artifacts that the applied literature has largely inherited without re-examining them, since chemical traps report a solvent-dependent fraction rather than a yield, the most widely used fluorogenic probe generates singlet oxygen itself, and spin trapping can overestimate the yield when the trapping amine quenches the excited sensitizer. The biological layers add uncertainty of their own, since the identity a cell encounters is set by the coating and the adsorbed protein corona rather than by the synthesized particle, while degradation, clearance and immune response are characterized sparsely and rarely in physiological media. The review closes with a minimum reporting set, drawn from practices already present in the corpus, that would make these studies comparable at little additional cost at the bench.