Aggregation-induced emission luminogens (AIEgens) as a kind of relatively new fluorescent molecules have garnered great attention in the field of chemo/biosensors, photoelectric devices and so on thanks to their high QY, good photostability and efficient ROS generation in the aggregated state. The direct covalent linked AIEgens have been widely used to construct photosensitizers for bioimaging, PDT, photothermal therapy and immunotherapy, but also presented challenges in terms of intricate synthesis and restricted structure modulation. With the benefits of straightforward operability and broad applicability, noncovalent strategy is gradually regarded as a fine alternative to smartly adjust photophysical properties and ROS efficiency of AIE photosensitizers. Organic macrocycles as the primary host compounds in supramolecular assembly can selectively encapsulate guest molecules in their intrinsic cavities to form complexes. Cyclodextrins (CDs) (including α-, β-and γ-CD) are a family of water-soluble macrocyclic oligosaccharides, giving a conelike molecular container, which have been widely employed in biomedical fields and pharmaceutical applications by virtue of high stability and excellent biocompatibility. In this work, we adopt host-guest strategy to construct a hypoxia-responsive supramolecular nanomaterials based on α-CD, red-emitting AIEgens and paclitaxel (PTX)based prodrug (named as PTX-NB), that surpasses hypoxia limitations and enhances the efficiency of chemotherapeutic prodrug release through PDT in solid tumor (Scheme 1). Cationic AIEgen composed of tetraphenylethylene (TPE), benzoselenadiazole and pyridinium (namely TPA-Py) or quinolinium salt (namely TPA-Qu) as a guest molecule can form supramolecular complex with α-CD in a 1:1 binding ratio through electrostatic interaction.