Browsing by Author "Maccarini, Paolo"

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    ItemOpen Access
    Plasmonic gold nanostars for synergistic photoimmunotherapy to treat cancer
    (Nanophotonics, 2021-09-02) Liu, Yang; Chorniak, Ericka; Odion, Ren; Etienne, Wiguins; Nair, Smita K; Maccarini, Paolo; Palmer, Gregory M; Inman, Brant A; Vo-Dinh, Tuan
    Cancer is the second leading cause of death and there is an urgent need to improve cancer management. We have developed an innovative cancer therapy named Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) by combining gold nanostars (GNS)-mediated photothermal ablation with checkpoint inhibitor immunotherapy. Our previous studies have demonstrated that SYMPHONY photoimmunotherapy not only treats the primary tumor but also dramatically amplifies anticancer immune responses in synergy with checkpoint blockade immunotherapy to treat remote and unresectable cancer metastasis. The SYMPHONY treatment also induces a 'cancer vaccine' effect leading to immunologic memory and prevents cancer recurrence in murine animal models. This manuscript provides an overview of our research activities on the SYMPHONY therapy with plasmonic GNS for cancer treatment.
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    Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study.
    (International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, 2020-01) Tan, Wei Phin; Chang, Andrew; Brousell, Steven C; Grimberg, Dominic C; Fantony, Joseph J; Longo, Thomas A; Etienne, Wiguins; Spasojevic, Ivan; Maccarini, Paolo; Inman, Brant A

    Background

    Hyperthermia (heating to 43 °C) activates the innate immune system and improves bladder cancer chemosensitivity.

    Objective

    To evaluate the tissue penetration and safety of convective hyperthermia combined with intravesical mitomycin C (MMC) pharmacokinetics in live porcine bladder models using the Combat bladder recirculation system (BRS).

    Methods

    Forty 60 kg-female swine were anesthetized and catheterized with a 3-way, 16 F catheter. The Combat device was used to heat the bladders to a target temperature of 43 °C with recirculating intravesical MMC at doses of 40, 80, and 120 mg. Dwell-heat time varied from 30-180 min. Rapid necropsy with immediate flash freezing of tissues, blood and urine occurred. MMC concentrations were measured by liquid chromatography tandem-mass spectrometry.

    Results

    The Combat BRS system was able to achieve target range temperature (42-44 °C) in 12 mins, and this temperature was maintained as long as the device was running. Two factors increased tissue penetration of MMC in the bladder: drug concentration, and the presence of heat. In the hyperthermia arm, MMC penetration saturated at 80 mg, suggesting that with heating, drug absorption may saturate and not require higher doses to achieve the maximal biological effect. Convective hyperthermia did not increase the MMC concentration in the liver, heart, kidney, spleen, lung, and lymph node tissue even at the 120 mg dose.

    Conclusions

    Convective bladder hyperthermia using the Combat BRS device is safe and the temperature can be maintained at 43 °C. Hyperthermia therapy may increase MMC penetration into the bladder wall but does not result in an increase of MMC levels in other organs.
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    ItemOpen Access
    Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) for the Treatment of Unresectable and Metastatic Cancers.
    (Scientific reports, 2017-08-17) Liu, Yang; Maccarini, Paolo; Palmer, Gregory M; Etienne, Wiguins; Zhao, Yulin; Lee, Chen-Ting; Ma, Xiumei; Inman, Brant A; Vo-Dinh, Tuan
    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.