Abstract
Metastatic spread is the mechanism in more than 90 percent of cancer deaths and current therapeutic options, such as systemic chemotherapy, are often ineffective. Here we provide a proof of principle for a novel two-pronged modality referred to as Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) having the potential to safely eradicate both primary tumors and distant metastatic foci. Using a combination of immune-checkpoint inhibition and plasmonic gold nanostar (GNS)–mediated photothermal therapy, we were able to achieve complete eradication of primary treated tumors and distant untreated tumors in some mice implanted with the MB49 bladder cancer cells. Delayed rechallenge with MB49 cancer cells injection in mice that appeared cured by SYMPHONY did not lead to new tumor formation after 60 days observation, indicating that SYMPHONY treatment induced effective long-lasting immunity against MB49 cancer cells.
Highlights
The immune system response is heightened by several temperature-induced mechanisms, such as antigen delivery by heat shock proteins (HSPs) and improved migration of lymphocytes to hot spots[5]
The unique tip-enhanced plasmonics property of gold nanostar (GNS) can be optimally tuned in the near infrared (NIR) tissue optical window, where photons can travel further in healthy tissue to be ‘captured’ and converted into heat by GNS taken up preferentially in cancer cells[15,16,17]
Is there an immediate killing effect at the site treated with light, but this treatment results in a general activation of the immune system, as evidenced by the fact that distant tumors not treated with light show cancer cell killing
Summary
Yang Liu[1,2], Paolo Maccarini[1], Gregory M. Using a combination of immune-checkpoint inhibition and plasmonic gold nanostar (GNS)–mediated photothermal therapy, we were able to achieve complete eradication of primary treated tumors and distant untreated tumors in some mice implanted with the MB49 bladder cancer cells. Immunotherapies can synergistically benefit from targeted thermal therapies, especially if mild hyperthermia (HT) is combined with precise thermal ablation of cancer cells[6]. Traditional HT modalities such as microwaves, radiofrequency and ultrasound can control macroscopic heating around the tumor region, but cannot precisely target or ablate cancer cells in a timely manner. Nanoparticle (NP)-mediated thermal therapy has recently demonstrated the potential to combine the advantages of precise cancer cell ablation[11] with benefits of mild HT in tumor microenvironments. Even for a high dose of GNS at 48 mg/kg, no morphology changes in hepatocytes were observed and the GNS dose was well tolerated
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