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Objective: To construct an analytical model instead of local effect modelingfor the prediction of the biological effectiveness of nanoparticleradiosensitization. Approach: An extended local effects model is first proposedwith a more comprehensive description of the nanoparticles mediated localkilling enhancements, but meanwhile puts forward challenging issues that remaindifficult and need to be further studied. As a novel method instead of localeffect modeling, a survival modification framework of compound Poisson additivekilling is proposed, as the consequence of an independent additive killing bythe assumed equivalent uniform doses of individual nanoparticles per cell underthe LQ model. A compound Poisson killing (CPK)model based on the framework isthus derived, giving a general expression of nanoparticle mediated LQ parametermodification. For practical use, a simplified form of the model is alsoderived, as a concentration dependent correction only to the {\alpha}parameter, with the relative correction (alpha"/alpha)) dominated by the meannumber, and affected by the agglomeration of nanoparticles per cell. Fordifferent agglomeration state, a monodispersion model of the dispersity factor{\eta}=1, and an agglomeration model of 2/3<{\eta}<1,are provided for practicalprediction of (alpha"/alpha) value respectively. Main results: Initialvalidation by the radiosensitization ofHepG2 cells by carbon dots showed a highaccuracy of the CPK model. In a safe range of concentration (0.003-0.03{\mu}g/{\mu}L)of the carbon dots, the prediction errors of the monodispersionand agglomeration models were both within 2%, relative to the clonogenicsurvival data of the sensitized HepG2 cells.

physics in medicine and biology/physics in medicine and biology

Nanoparticle Radiosensitization: from extended local effect modeling to  a survival modificationframework of compound Poisson additive killing and its  carbon dots validation