Room-temperature phosphorescence (RTP) has much longer lifetime and much broader Stokes shift than those of traditional fluorescence. However, deoxygenation procedure has always been troubling the development and application of RTP in biosystem. Herein it was unexpectedly found that the crystalline nanoparticles (CNs) generated by the ethanol solution of 5-iodosalicylic acid (5-Isal) being titrated by the aqueous solution of PbCl2 (CNs 1), and titrating dichloromethane solution of 1,2-di(4-pyridyl)ethylene (BPE) or reversely titrating (CNs 2), respectively, can emit RTP without any deoxygenation operation, implying the great potential for bioimaging. The FT-IR spectroscopy predicts and XRD data reveal that 5 Isal can assemble into supramolecular cocrystals with lead ion (Cry 1) and BPE (Cry 2) through synergism of hydrogen bonding, halogen bonding, pi pi it stacking and other noncovalent interactions. The powder XRD, as well as reveals the homogeneity of CNs 1 and Cry 1, together with HPLC confirms that the CNs 2 is the physical mixture of 5-Isal and BPE but the nanometer-sized Cry 2 due to difference in solubility. Moreover, the RTP emissions and decays of the suspension powder of cocrystals in aqueous solution were investigated. The RTP at 505 nm and 545 nm for Cry 1, and 528 nm for Cry 2 under the excitation wavelength at 375 nm were observed, which were in accord with those of the CNs. Due to the compact structure of CNs and cocrystals, the dissolved oxygen was prevented from freely contacting with 5-Isal, which protected the inner excited triplet state of 5-Isal. The synergism of multi-weak interactions in aqueous solution should be instructive for developing self-protective RTP nanomaterials. (C) 2016 Elsevier B.V. All rights reserved.