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

Abstract

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

Tumor pH-Responsive Nanocarriers With Light-Activatable Drug Release for Chemo-Photodynamic Therapy of Breast Cancer

“…The light-triggered DOX release of DA TAT-NP Ce6 achieved cascaded chemo-PDT for breast cancer. Compared to the previous studies which focused on CPPs presenting and light-controlled cargo release alone ( Jiang et al, 2018 ; Xu et al, 2021 ; Zhang et al, 2021 ), we integrated both functions in DA TAT-NP Ce6 through a facile mixed micelle method. More interestingly, the ratio of TAT-PEG-PHEP and PEG-PPE-DOX, therapeutic agent, and photosensitizer could be easily adjusted during micelle preparation to regulate the performance of DA TAT-NP Ce6 (e.g., targeting ability and drug loading content) for more specific and precise treatment of various cancers in the future.…”

Immunotherapy-based novel nanoparticles in the treatment of gastrointestinal cancer: Trends and challenges

“…Hence, ICD can improve the efficacy of ICB treatment by increasing tumor immunogenicity. According to the therapeutic strategies mentioned above, Xu et al [ 75 ] designed a cyclic arginine-glycine-aspartic acid peptide-modified self-assembling polymer-based NDDS. Cancer cells were damaged by PDT and chemotherapy, while induced ICD and enhanced tumor immunogenicity provided a suitable immune microenvironment for ICB treatment.…”

Aggregation-Induced Emission Luminogens for Enhanced Photodynamic Therapy: From Organelle Targeting to Tumor Targeting

“…There are two main approaches: (1) Most examples target lysosomes through the modification of lipophilic amines with the addition of morpholines and other amine groups [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. (2) A promotion of endocytosis can also transport PSs from the endosome into the cell and capture them in the lysosome [ 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ].…”