In Vivo-assembled phthalocyanine/albumin supramolecular complexes combined with a hypoxia-activated prodrug for enhanced photodynamic immunotherapy of cancer

Li, Xingshu; Jeon, Yun Hui; Kwon, Nahyun; Park, June; Guo, Tian; Kim, Hang Rae; Huang, Jian; Lee, Dong Sup; Yoon, Juyoung

doi:10.1016/j.biomaterials.2020.120430

Cited by 84 publications

(46 citation statements)

References 49 publications

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“…In the past few years, extensive research has been conducted to overcome drug resistance and improve the prognosis of TNBC [48]. The combination of chemotherapeutics with SDDS, particularly with stimuli-responsive systems that are able to control drug biodistribution and release in response to speci c stimuli, either exogenous (temperature, magnetic eld, ultrasound, light or electric pulses) or endogenous (changes in pH, enzyme concentration or redox gradients) has been explored for metastatic breast cancer [50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Synergistic Cascade Strategy Based on Modifying Tumor Microenvironment for Enhanced Breast Cancer Therapy

Zhang

Gao

et al. 2021

Preprint

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Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with very few treatment options. Although tumor-targeted nanomedicines hold great promise for the treatment of TNBC, the tumor microenvironment (TME) continues to be a major cause of failure in nanotherapy and immunotherapy. To overcome this barrier, we designed a new synergistic cascade strategy (SCS) that uses mild hyperthermia and smart drug delivery system (SDDS) to alter TME resistance in order to improve drug delivery and therapeutic efficacy of TNBC.Methods: Mild hyperthermia was produced by microwave (MW) irradiation. SDDS were formulated with thermosensitive polymer-lipid nanoparticles (HA-BNPs@Ptx), composed of polymer PLGA, phospholipid DPPC, hyaluronic acid (HA, a differentiation-44 targeted molecule, also known as CD44), 1-butyl-3-methylimidazolium-L-lactate (BML, a MW sensitizer) and paclitaxel (Ptx, chemotherapy drug). 4T1 breast tumor-bearing mice were treated with two-step MW combined with HA-BNPs@Ptx. Tumors in mice were pretreated with 1st MW irradiation prior to nanoparticle injection to modify TME and promote TME and promoting nanoparticle uptake and retention. The 2nd MW irradiation was performed on the tumor 24 h after the injection HA-BNPs@Ptx to produce a synergistic cascade effect through activating BML, thus enhancing hyperthermia effect, and instantly releasing Ptx at the tumor site.Results: Multifunctional CD44-targeted nanoparticles HA-BNPs@Ptx were successfully prepared and validated in-vitro. After the 1st MW irradiation of tumors in mice, the intratumoral perfusion increased by 2 times and the nanoparticle uptake augmented by 7 times. With the 2nd MW irradiation, remarkable anti-tumor effects were obtained with the inhibition rate up to 88%. In addition, immunohistochemical analysis showed that SCS therapy could not only promote the tumor cells apoptosis, trigger the immune response of cytotoxic T lymphocytes, but also significantly reduce the lung metastasis. Conclusions: The SCS using mild hyperthermia combined with smart drug delivery system, can significantly improve the efficacy of TNBC treatment in mice by modifying TME and hyperthermia-mediated EPR effects.

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Section: Discussionmentioning

confidence: 99%

Synergistic Cascade Strategy Based on Modifying Tumor Microenvironment for Enhanced Breast Cancer Therapy

Zhang

Gao

et al. 2021

Preprint

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“…Hepatocellular carcinoma (HCC) is the third leading cause of cancer death in the world [ 1 ]. Vast majority of patients are diagnosed at advanced stage that lose the chance of radical surgery, and the high probability of recurrence and metastasis leading to more than 90% of cancer-caused deaths is the major challenge in clinical treatment of HCC [ 2 – 4 ]. The current treatment strategies still cannot achieve satisfactory therapeutic effect, especially in unresectable HCC patients.…”

Section: Introductionmentioning

confidence: 99%

“…Many other therapeutic methods, such as photodynamic therapy (PDT) and chemotherapy, have been exploited to elicit an anti-tumor immune response [ 2 , 16 – 22 ]. PDT employs a combination of photosensitizer, light and oxygen to produce large amounts of reactive oxygen species (ROS) for inducing the immunogenic cell death (ICD) and releasing TAA [ 18 – 29 ].…”

Section: Introductionmentioning

confidence: 99%

“…PDT employs a combination of photosensitizer, light and oxygen to produce large amounts of reactive oxygen species (ROS) for inducing the immunogenic cell death (ICD) and releasing TAA [ 18 – 29 ]. However, limited by the tissue penetration and tumor hypoxia microenvironment, PDT only shows marginal to moderate therapeutic performance [ 2 , 13 , 30 ]. Besides, although PDT can kill some tumor cells and generate certain levels of anti-tumor immune responses, PDT alone is usually insufficient to inhibit the growth of residual tumor cells in the body after PDT [ 2 , 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, limited by the tissue penetration and tumor hypoxia microenvironment, PDT only shows marginal to moderate therapeutic performance [ 2 , 13 , 30 ]. Besides, although PDT can kill some tumor cells and generate certain levels of anti-tumor immune responses, PDT alone is usually insufficient to inhibit the growth of residual tumor cells in the body after PDT [ 2 , 31 , 32 ]. For chemotherapy, increasing evidences reveal that chemotherapy may increase tumor sensitivity toward immunotherapy [ 16 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Chemo-photodynamic therapy with light-triggered disassembly of theranostic nanoplatform in combination with checkpoint blockade for immunotherapy of hepatocellular carcinoma

Zheng

Cheng

et al. 2021

J Nanobiotechnol

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Background Hepatocellular carcinoma (HCC) is a common malignant tumor with high rate of metastasis and recurrence. Although immune checkpoint blockade (ICB) has emerged as a promising type of immunotherapy in advanced HCC, treatment with ICB alone achieves an objective remission rate less than 20%. Thus, combination therapy strategies is needed to improve the treatment response rate and therapeutic effect. Methods A light-triggered disassembly of nanoplatform (TB/PTX@RTK) co-loaded an aggregation induced emission (AIE) photosensitizer (TB) and paclitaxel (PTX) was prepared for on-command drug release and synergistic chemo-photodynamic therapy (chemo-PDT). Nano-micelles were characterized for drug loading content, hydrodynamic size, absorption and emission spectra, reactive oxygen species production, and PTX release from micelles. The targeted fluorescence imaging of TB/PTX@RTK micelles and the synergistic anti-tumor efficacy of TB/PTX@RTK micelles-mediated chemo-PDT combined with anti-PD-L1 were assessed both in vitro and in vivo. Results The TB/PTX@RTK micelles could specifically accumulate at the tumor site through cRGD-mediated active target and facilitate image-guided PDT for tumor ablation. Once irradiated by light, the AIE photosensitizer of TB could produce ROS for PDT, and the thioketal linker could be cleaved by ROS to precise release of PTX in tumor cells. Chemo-PDT could not only synergistically inhibit tumor growth, but also induce immunogenic cell death and elicit anti-tumor immune response. Meanwhile, chemo-PDT significantly upregulated the expression of PD-L1 on tumor cell surface which could efficiently synergize with anti-PD-L1 monoclonal antibodies to induce an abscopal effect, and establish long-term immunological memory to inhibit tumor relapse and metastasis. Conclusion Our results suggest that the combination of TB/PTX@RTK micelle-mediated chemo-PDT with anti-PD-L1 monoclonal antibodies can synergistically enhance systemic anti-tumor effects, and provide a novel insight into the development of new nanomedicine with precise controlled release and multimodal therapy to enhance the therapeutic efficacy of HCC. Graphical Abstract

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Photosensitizer with High Efficiency Generated in Cells via Light‐Induced Self‐Oligomerization of 4,6‐Dibromothieno[3,4‐b]thiophene Compound Entailing a Triphenyl Phosphonium Group

Wang

Zhong

et al. 2021

Adv Healthcare Materials

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Photodynamic therapy (PDT) has emerged as an attractive alternative in cancer therapy, but therapeutic effects suffer from low photosensitizing efficiency and poor retention of photosensitizes in cancer cells. This paper reports the photosensitizers which show absorption and emission in the long‐wavelength region and high photosensitizing efficiency can be formed in situ in cells from 4,6‐dibromothieno[3,4‐b]thiophene derivative (TT‐5‐P) after white light irradiation. The self‐oligomerization of TT‐5‐P is uptaken in cells upon light irradiation‐induced cell apoptosis simultaneously and efficiently. In addition, the formation of oligomers (TT‐5‐Ps) enhances the retention time in cells remarkably, which is advantageous for boosting the photodynamic therapy efficiency. Moreover, the selectivity toward tumor cells of TT‐5‐P can be improved obviously via the formation of complex of TT‐5‐P with albumin. This in situ photoinduced self‐oligomerization strategy can be utilized to design effective biomaterials for long‐term imaging and improved therapy.

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In Vivo-assembled phthalocyanine/albumin supramolecular complexes combined with a hypoxia-activated prodrug for enhanced photodynamic immunotherapy of cancer

Cited by 84 publications

References 49 publications

Synergistic Cascade Strategy Based on Modifying Tumor Microenvironment for Enhanced Breast Cancer Therapy

Synergistic Cascade Strategy Based on Modifying Tumor Microenvironment for Enhanced Breast Cancer Therapy

Chemo-photodynamic therapy with light-triggered disassembly of theranostic nanoplatform in combination with checkpoint blockade for immunotherapy of hepatocellular carcinoma

Photosensitizer with High Efficiency Generated in Cells via Light‐Induced Self‐Oligomerization of 4,6‐Dibromothieno[3,4‐b]thiophene Compound Entailing a Triphenyl Phosphonium Group

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