Treat the “Untreatable” by a Photothermal Agent: Triggering Heat and Immunological Responses for Rabies Virus Inactivation

Abstract

Rabies is a fatal neurological zoonotic disease caused by the rabies virus (RABV), and the approved post‐exposure prophylaxis (PEP) procedure remains unavailable in areas with inadequate medical systems. Although strategies have been proposed for PEP and postinfection treatment (PIT), because of the complexity of the treatment procedures and the limited curative outcome, developing an effective treatment strategy remains a holy grail in rabies research. Herein, a facile approach is proposed involving photothermal therapy (PTT) and photothermally triggered immunological effects to realize effective PEP and PIT simultaneously. The designed photothermal agent (N+TT‐mCB nanoparticles) featured positively charged functional groups and high photo‐to‐heat efficiency, which are favorable for virus targeting and inactivation. The level of the virus at the site of infection in mice is significantly decreased upon treatment with orthotopic PTT, and the transfer of the virus to the brain is significantly inhibited. Furthermore, the survival ratio of the mice three days postinfection is increased by intracranial injection of N+TT‐mCB and laser irradiation. Overall, this work provides a platform for the effective treatment of RABV and opens a new avenue for future antiviral studies.

NIR-II-absorbing diimmonium polymer agent achieves excellent photothermal therapy with induction of tumor immunogenic cell death

“…Mild photothermal therapy is reported to reprogram the “cold” TME [ 21 – 26 ]. It has been demonstrated that PTT can cause immunogenic cell death (ICD) [ 27 , 28 ], generating tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs), which could activate dendritic cells and stimulate an antigen presentation to T cells [ 12 , 29 – 32 ]. However, currently most of the light-absorbed agents are in NIR-I window (700 − 900 nm) for imaging and phototherapy.…”

Photothermal Nanomaterials: A Powerful Light-to-Heat Converter

“…Since silica-cored Au nanoshells served as the first photothermal nanomaterials for clinical use, more and more inorganic agents with strong absorption in the NIR region, high chemical stability, adjustable water solubility, and minimal cytotoxicity have entered clinical trials. , Clinical trials have also been underway for small organic molecules due to their good biodegradability, good repeatability, and simple preparation. , Nevertheless, the major challenges for the clinical implementation of photothermal nanomaterials are the complex metabolism and excretion behaviors . The representative works on PTT with diverse photothermal nanomaterials in recent years − are summarized in Table .…”

Molecular Engineering of AIE Photosensitizers for Inactivation of Rabies Virus

“…Moreover, it has been demonstrated that PTT can suppress viruses by inhibiting them locally through thermal effects and photothermal-triggered inflammatory reactions. [53,54] However, the photothermal effect of PTT can lead to tissue damage, causing physical and emotional discomfort during the therapy process, even though it is gradually recoverable. [53] To overcome these limitations, a synergistic approach through the combined use of PTT and PDT is proposed.…”

“…[53,54] However, the photothermal effect of PTT can lead to tissue damage, causing physical and emotional discomfort during the therapy process, even though it is gradually recoverable. [53] To overcome these limitations, a synergistic approach through the combined use of PTT and PDT is proposed. This approach leverages the low toxicity and minimal side effects of phototherapy while enabling the two modalities to work in concert, [55] leading to enhanced an-tiviral efficacy.…”