Combining Photothermal‐Photodynamic Therapy Mediated by Nanomaterials with Immune Checkpoint Blockade for Metastatic Cancer Treatment and Creation of Immune Memory

Lima‐Sousa, Rita; Melo, Bruna L.; Alves, Cátia G.; Moreira, André F.; Mendonça, António; Correia, Ilídio J.; Melo‐Diogo, Duarte de

doi:10.1002/adfm.202010777

Cited by 40 publications

(26 citation statements)

References 128 publications

(192 reference statements)

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“…Regulatory T cells (Treg) are major immune suppressive cells and thus decreased number of Treg cells indicates an antitumor immune responses. [ 26 ] Treg cells (defined as CD3 + CD4 + CD25 + ) were significantly decreased in all iLNTB‐treated groups (Figure S4g, Supporting Information). Compared to the only Dox group, T‐iLNC combined with Dox group shows the difference only in the Treg cell ratio with a slight increase of CD8 to CD4 ratio, but no significant effects on the tumor myeloid cell parameters and tumor growth.…”

Section: Resultsmentioning

confidence: 99%

Dual‐Targeted Lipid Nanotherapeutic Boost for Chemo‐Immunotherapy of Cancer

et al. 2022

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malignant cells. Immune checkpoint inhibitors (ICIs), such as anti-PD1 and anti-CTLA4 antibodies, are among the most successful immunotherapy modalities that have shown therapeutic benefits in various types of cancers, from melanoma to lung cancer. [1] However, only a minority of cancer patients are responsive to ICIs therapy, depending on their immunophenotype and cancer genotype. [2] Chemo-immunotherapy is a combination of "standard-of-care" chemotherapy with immunotherapy, mostly ICIs such as nivolumab and pembrolizumab that shows therapeutic benefit in the clinic and success in phase III trials. [3] Yet, many patients are still poorly responsive to this combination therapy and nanotherapeutics could be a novel strategy for the improvement of chemo-immunotherapy.The tumor immune microenvironment is enriched with various immune cells from myeloid cells to lymphocytes. Tumor myeloid cells including monocytes and macrophages are recruited by the inflamed cancer cell niche and paradoxically induce "immunosuppressive" status in solid tumors. [2b,4] In particular, tumor-associated macrophages (TAM) that are originated from tumor-infiltrated monocytes [5] directly remodel the tumor immune microenvironment by physically impeding infiltration of cytotoxic CD8 + T lymphocytes and Chemo-immunotherapy is a combination of "standard-of-care" chemotherapy with immunotherapy and it is considered the most advanced therapeutic modality for various types of cancers. However, many cancer patients still poorly respond to current regimen of chemo-immunotherapy and suggest nanotherapeutics as a boosting agent. Recently, heme oxygenase-1 (HO1) is shown to act as an immunotherapeutic molecule in tumor myeloid cells, in addition to general chemoresistance function in cancer cells suggesting that HO1-targeted therapeutics can become a novel, optimal strategy for boosting chemo-immunotherapy in the clinic. Currently the available HO1-inhibitors demonstrate serious adverse effects in clinical use. Herein, tumor myeloid cell-and cancer cell-dual targeted HO1-inhibiting lipid nanotherapeutic boost (T-iLNTB) is developed using RNAiloaded lipid nanoparticles. T-iLNTB-mediated HO1-inhibition sensitizes cancer cells to "standard-of-care" chemotherapeutics by increasing immunogenic cell death, and directly reprograms tumor myeloid cells with distinguished phenotype. Furthermore, tumor myeloid cell reprogramming by T-iLNTB induces CD8 + cytotoxic T cell recruitment, which drives "Cold-to-Hot" transition and correlates with improved responsiveness to immune checkpoint inhibitor in combination therapy. Finally, ex vivo study proves that HO1-inhibition directly affects tumor macrophage differentiation. This study demonstrates the potential of T-iLNTB as a novel therapeutic modality for boosting chemo-immunotherapy.

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Section: Resultsmentioning

confidence: 99%

Dual‐Targeted Lipid Nanotherapeutic Boost for Chemo‐Immunotherapy of Cancer

et al. 2022

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“…Expectedly, the results manifested mCuLP group (6.32 μmol•g −1 ) had a more remarked lactate depletion effect than the PBS (11.96 μmol•g −1 ), LOX (11.30 μmol•g −1 ), and mCuP+NIR groups (8.21 μmol•g −1 ), due to tumor accumulation of mCuLP nanosystems and catalytic closedloop for lactate oxidation (Figure 5e). Furthermore, because of blood vessel dilation and oxygen delivery that were boosted by photothermal irradiation, 62 intratumoral lactate of mCuLP +NIR (4.09 μmol•g −1 ) was reduced by 65.8%, which showed more enhanced lactate depletion than the mCuLP group (47.2%). In addition, the concentration of intracellular pyruvate was measured after the tumor cells lysed.…”

Section: Photothermal Conversion Of Mculp and Catalysis Retention Of Loxmentioning

confidence: 98%

Dual Closed-Loop of Catalyzed Lactate Depletion and Immune Response to Potentiate Photothermal Immunotherapy

Zheng

Liu

et al. 2022

ACS Appl. Mater. Interfaces

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Lactate accumulation in the solid tumor is highly relevant to the immunosuppressive tumor microenvironment (TME). Targeting lactate metabolism significantly enhances the efficacy of immunotherapy. However, lactate depletion by lactate oxidase (LOX) consumes oxygen and results in the aggravated hypoxia situation, counteracting the benefit of lactate depletion. Beyond the TME regulation, it is necessary to initiate the effective immunity cycle for therapeutic purposes. In this fashion, dual close-loop of catalyzed lactate depletion and immune response by a rational material design are established to address this issue. Here, we constructed PEG-modified mesoporous polydopamine nanoparticles with Cu2+ chelation and LOX encapsulation (denoted as mCuLP). After mCuLP nanosystems targeting into the tumor sites, released LOX consumes lactate to H2O2. Subsequently, the produced H2O2 is further catalyzed by Cu2+-chelated mPDA to produce oxygen, supplying the oxygen source for the closed-loop of lactate depletion. Meanwhile, the mild PTT caused by the photothermal mPDA induces ICD of tumor cells to promote DC maturation and then T lymphocyte infiltration to kill tumor cells, which forms another closed-loop for cancer immunity. Therefore, this dual closed-loop strategy of mCuLP nanosystems effectively inhibits tumor growth, providing a promising treatment modality to cancer immunotherapy.

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“…With a view towards more effective cancer treatment, collaborative treatments including imaging‐guided drug delivery, phototherapy and PDT‐PTT combination therapy are becoming increasingly attractive. [ 269–271 ]…”

Section: Applicationsmentioning

confidence: 99%

“…With a view towards more effective cancer treatment, collaborative treatments including imaging-guided drug delivery, phototherapy and PDT-PTT combination therapy are becoming increasingly attractive. [269][270][271] Imaging-guided treatment methods can overcome traditional issues in cancer therapies insufficient drug concentration, high systemic toxicity, severe side effects, and lack of monitoring. As a non-invasive strategy, advanced image analysis technologies can be used for the early diagnosis of cancer and provide a reliable basis for personalized treatment.…”

Section: Synergistic Treatmentmentioning

confidence: 99%