Perfluorocarbon‐Loaded and Redox‐Activatable Photosensitizing Agent with Oxygen Supply for Enhancement of Fluorescence/Photoacoustic Imaging Guided Tumor Photodynamic Therapy

Abstract

The wide clinical application of photodynamic therapy (PDT) is hampered by poor water solubility, low tumor selectivity, and nonspecific activation of photosensitizers, as well as tumor hypoxia which is common for most solid tumors. To overcome these limitations, tumor-targeting, redox-activatable, and oxygen self-enriched theranostic nanoparticles are developed by synthesizing chlorin e6 (Ce6) conjugated hyaluronic acid (HA) with reducible disulfide bonds (HSC) and encapsulating perfluorohexane (PFH) within the nanoparticles (PFH@HSC). The fluorescence and phototoxicity of PFH@HSC nanoparticles are greatly inhibited by a self-quenching effect in an aqueous environment. However, after accumulating in tumors through passive and active tumor-targeting, PFH@HSC appear to be activated from "OFF" to "ON" in photoactivity by the redox-responsive destruction of the vehicle's structure. In addition, PFH@HSC can load oxygen within lungs during blood circulation, and the oxygen dissolved in PFH is slowly released and diffuses over the entire tumor, finally resulting in remarkable tumor hypoxia relief and enhancement of PDT efficacy by generating more singlet oxygen. Taking advantage of the excellent imaging performance of Ce6, the tumor accumulation of PFH@HSC can be monitored by fluorescent and photoacoustic imaging after intravenous administration into tumor-bearing mice. This PFH@HSC nanoparticle might have good potential for dual imaging-guided PDT in hypoxic solid tumor treatment.

In‐Situ Oxygen‐Evolving Photoactive Nanococktail: The Future of Hypoxic Tumour Photodynamic Therapy

“…have reported tumour-targeting perfluorocarbon-loaded, oxygen self-enriched nanoparticles developed from hyaluronic acid-conjugated chlorin e6 (a wellknownp hotosensitizer);t hey encapsulated perfluorohexane within the nanoparticlest oo vercome tumour hypoxia-related resistance in PDT. [14] The redox-activatable nanoparticles are reported to load oxygen from the lungs and then releasei t within the hypoxicc ore of tumours to supply the required O 2 for PDT.M oreover,d ue to the presence of chlorin e6, an excellent imaging agent, the nanoparticlesa re of significance for developing imaging-guided PDT.…”

Application of nanotechnology for enhancing photodynamic therapy via ameliorating, neglecting, or exploiting tumor hypoxia

“…To further overcome the nonspecific activation of photosensitizers, in our recent work, we developed an activatable nano‐photosensitizer via a redox‐responsive turn‐on strategy incorporated with PFH for oxygen supply to strengthen PDT 77 . In brief, photosensitizer Ce6 was conjugated to the backbone of natural polysaccharide HA via a disulfide bond to obtain amphiphilic HSC conjugates with aqueous self‐assembly properties 78 .…”

Rational design of block copolymer self-assemblies in photodynamic therapy

“…Recent efforts in targeting through the hydrophilic block are summarized in Table 3. Carbohydrates have been used in order to confer targeting properties and they are often modified by grafting the hydrophobic photosensitizers in order to yield the amphiphilic properties necessary for self-assembly [93,111,112]. Among the targeting molecules, hyaluronic acid [111,112] is known to interact with CD44 over-expressed by some tumor cells.…”