Scheme 1.

(A) Schematic illustration of the enhanced fluorescence imaging based on HTP-BM/CFN in terms of manner as two-stage “AND” logic gate. (B). Schematic illustration of the multifunctional assemblies (HTP-BM/CFN) as fluorescent indicators of hypoxia, as well as photosensitizers that normalize tumor hypoxic heterogeneity: (C). Overexpressed folate receptors recruit folate-decorated HTP-BM/CFN to be enriched at tumor sites, followed by disassembly of the shell layers, release of the fluorescent indicator (CNP) and photosensitizer. The CNP is turned on under hypoxia-induced NTR high expression. (D). Heterogeneous fluorescence feedback appears within a single tumor with spatial heterogeneity of hypoxic regions. After HTP-BM core in GSH induced dissociation state exert a phototherapeutic effect upon the laser treatment, the hypoxia is enhanced with expanded hypoxic region regulated by PDT process, stimulating an enhanced and homogenized trend of fluorescence over the whole tumor. (E). Enhanced PDT efficiency with imaging monitoring was achieved by depleting GSH and elevating ROS production during cellular HTP degradation together with up-regulation of NTR.