Immunogenic cell death (ICD)-associated immunogenicity can be evoked through reactive oxygen species (ROS) produced via endoplasmic reticulum (ER) stress. In this study, we generate a double ER-targeting strategy to realize photodynamic therapy (PDT) photothermal therapy (PTT) immunotherapy. This nanosystem consists of ER-targeting pardaxin (FAL) peptides modified-, indocyanine green (ICG) conjugated- hollow gold nanospheres (FAL-ICG-HAuNS), together with an oxygen-delivering hemoglobin (Hb) liposome (FAL-Hb lipo), designed to reverse hypoxia. Compared with non-targeting nanosystems, the ER-targeting naosystem induces robust ER stress and calreticulin (CRT) exposure on the cell surface under near-infrared (NIR) light irradiation. CRT, a marker for ICD, acts as an ‘eat me’ signal to stimulate the antigen presenting function of dendritic cells. As a result, a series of immunological responses are activated, including CD8 + T cell proliferation and cytotoxic cytokine secretion. In conclusion, ER-targeting PDT-PTT promoted ICD-associated immunotherapy through direct ROS-based ER stress and exhibited enhanced anti-tumour efficacy.

The development of smart theranostic systems with favourable biocompatibility, high loading efficiency, excellent circulation stability, potent anti-tumour activity, and multimodal diagnostic functionalities is of importance for future clinical application. The premature burst release and poor degradation kinetics indicative of polymer-based nanomedicines remain the major obstacles for clinical translation. Herein we prepare theranostic shell-crosslinked nanoparticles (SCNPs) using a β-cyclodextrin-based polyrotaxane (PDI-PCL-b-PEG-RGD⊃β-CD-NH2) to avoid premature drug leakage and achieve precisely controllable release, enhancing the maximum tolerated dose of the supramolecular nanomedicines. cRGDfK and perylene diimide are chosen as the stoppers of PDI-PCL-b-PEG-RGD⊃β-CD-NH2, endowing the resultant SCNPs with excellent integrin targeting ability, photothermal effect, and photoacoustic capability. In vivo anti-tumour studies demonstrate that drug-loaded SCNPs completely eliminate the subcutaneous tumours without recurrence after a single-dose injection combining chemotherapy and photothermal therapy. These supramolecular nanomedicines also exhibit excellent anti-tumour performance against orthotopic breast cancer and prevent lung metastasis with negligible systemic toxicity.

A convenient and feasible therapeutic strategy for malignant and metastatic tumors was constructed here by combining photothermal ablation (PTA)-based laser immunotherapy with perdurable PD-1 blockade immunotherapy. Hollow gold nanoshells (HAuNS, a photothermal agent) and AUNP12 (an anti PD-1 peptide, APP) were co-encapsulated into poly(lactic- co-glycolic) acid (PLGA) nanoparticles. Unlike monoclonal PD-1/PD-L1 antibodies, PD-1 peptide inhibitor shows lower cost and immunotoxicity but needs frequent administration due to its rapid clearance in vivo. Our data here showed that the formed HAuNS- and APP-loaded PLGA nanoparticles (AA@PN) could maintain release periods of up to 40 days for the peptide, and a single intratumoral injection of AA@PN could replace the frequent administration of free APP. After the administration of AA@PN and irradiation with a near-infrared laser at the tumor site, an excellent killing effect on the primary tumor cells was achieved by the PTA. The nanoparticles also played a vaccine-like role under the adjuvant of cytosine-phospho-guanine (CpG) oligodeoxynucleotide and generated a localized antitumor-immune response. Furthermore, sustained APP release with laser-dependent transient triggering could induce the blockage of PD-1/PD-L1 pathway to activate T cells, thus subsequently generating a systemic immune response. Our data demonstrated that the PTA combined with perdurable PD-1 blocking could efficiently eradicate the primary tumors and inhibit the growth of metastatic tumors as well as their formation. The present study provides a promising therapeutic strategy for the treatment of advanced cancer with metastasis and presents a valuable reference for obtaining better outcomes in clinical cancer immunotherapy.

Artificial light-harvesting systems in aqueous media which mimic nature are of significant importance; however, they are often restrained by the solubility and the undesired aggregation-caused quenching effect of the hydrophobic chromophores. Here, we report a generalized strategy toward the construction of efficient artificial lightharvesting systems based on supramolecular peptide nanotubes in water. By molecularly aligning the hydrophobic chromophores along the nanotubes in a slipped manner, an artificial light-harvesting system with a two-step sequential Forster resonance energy transfer process is successfully fabricated, showing an energy transfer efficiency up to 95% and a remarkably high fluorescence quantum yield of 30%, along with high stability. Furthermore, the spectral emission could be continuously tuned from blue through green to orange, as well as outputted as a white light continuum with a fluorescence quantum yield of 29.9%. Our findings provide a versatile approach of designing efficient artificial light-harvesting systems and constructing highly emissive organic materials in aqueous media.