Ultrafast Low-Temperature Photothermal Therapy Activates Autophagy and Recovers Immunity for Efficient Antitumor Treatment

Abstract

Conventional therapeutic approaches to treat malignant tumors such as surgery, chemotherapy, or radiotherapy often lead to poor therapeutic results, great pain, economic burden, and risk of recurrence and may even increase the difficulty in treating the patient. Long-term drug administration and systemic drug delivery for cancer chemotherapy would be accompanied by drug resistance or unpredictable side effects. Thus, the use of photothermal therapy, a relatively rapid tumor elimination technique that regulates autophagy and exerts an antitumor effect, represents a novel solution to these problems. Heat shock protein 90 (HSP90), a protein that reduces photothermal or hypothermic efficacy, is closely related to AKT (protein kinase B) and autophagy. Therefore, it was hypothesized that autophagy could be controlled to eliminate tumors by combining exogenous light with a selective HSP90 inhibitor, for example, SNX-2112. In this study, an efficient tumor-killing strategy using graphene oxide loaded with SNX-2112 and folic acid for ultrafast low-temperature photothermal therapy (LTPTT) is reported. A unique mechanism that achieves remarkable therapeutic performance was discovered, where overactivated autophagy induced by ultrafast LTPTT led to direct apoptosis of tumors and enabled functional recovery of T cells to promote natural immunity for actively participating in the attack against tumors. This LTPTT approach resulted in residual tumor cells being rendered in an "injured" state, opening up the possibility of concurrent antitumor and antirecurrence treatment.

Hydroxysafflor yellow�A induces autophagy in human liver cancer cells by regulating Beclin�1 and ERK expression

“…Autophagy has a two-way effect on tumor progression. A number of studies have reported that autophagy can inhibit tumorigenesis (13)(14)(15); however, when tumors form under oxygen-deficient conditions, autophagy is able to promote tumor growth and survival (16). Additionally, >30 autophagy-associated proteins have been identified, including light chain 3 (LC3), which was the first autophagosome protein marker to be discovered, the Beclin 1 complex and p62 (17)(18)(19).…”

Solutions to the Drawbacks of Photothermal and Photodynamic Cancer Therapy

“…Similarly, Shao and coworkers [ 35 ] loaded SNX‐2112, a small molecule inhibitor of HSP90, on 2D graphene nanoplatform to achieve the effect of low‐temperature PTT. They found that, during this process, low‐temperature PTT triggered excessive autophagic death of tumor cells, and this therapy method can achieve a long‐term tumor suppression effect through the activation of body's immune system.…”

“…The article starts with the limitations of phototherapy, summarizes the solutions proposed by researchers in recent years aiming to solve the problems of phototherapy, and provides more comprehensive understanding of phototherapy in antitumor research. The article content includes solutions for thermal damage to normal tissues caused by PTT, [ 34–41 ] solutions for insufficient treatment effect of PTT, solutions for extremely short life and short diffusion distance of ROS in PDT, solutions for lack of oxygen that can produce ROS in PDT, solutions for poor penetration effect of excitation light source, and solutions for insufficient treatment effect of single PDT. Scheme is the sketch map of this topic.…”

Low-Temperature Photothermal Therapy: Strategies and Applications

“…However, a number of studies have demonstrated that some kinds of tumors were not vulnerable to ICB treatments because there are few TILs and low PD-L1 content in these tumor tissues [ 248 – 251 ]. Fortunately, due to its excellent potential for facilitating the recruitment of TILs and its capacity of inducing the elevated expression of PD-L1 on the plasma membranes of cancer cells, mild PTT is able to provide a possibility of remodeling the TME and enhancing the efficacy of ICB-based immunotherapy [ 239 , 251 – 255 ]. For instance, Huang et al encapsulated both IR820 and PD-L1 antibody (aPD-L1), which is capable of interfering with the interaction of programmed death protein 1 (PD-1) with PD-L1, into an injectable lipid gel (LG) depot which could undergo thermally reversible gel-to-sol phase transition [ 256 ].…”