Although low-dose CT imaging has attracted a great interest due to its reduced radiation risk to the patients, it suffers from severe and complex noise. Recent fully-supervised methods have shown impressive performances on CT denoising task. However, they require a huge amount of paired normal-dose and low-dose CT images, which is generally unavailable in real clinical practice. To address this problem, we propose a weakly-supervised denoising framework that generates paired original and noisier CT images from unpaired CT images using a physics-based noise model. Our denoising framework also includes a progressive denoising module that bypasses the challenges of mapping from low-dose to normal-dose CT images directly via progressively compensating the small noise gap. To quantitatively evaluate diagnostic image quality, we present the noise power spectrum and signal detection accuracy, which are well correlated with the visual inspection. The experimental results demonstrate that our method achieves remarkable performances, even superior to fully-supervised CT denoising with respect to the signal detectability. Moreover, our framework increases the flexibility in data collection, allowing us to utilize any unpaired data at any dose levels. (c) 2021 Elsevier B.V. All rights reserved.