Bioinspired Hybrid Protein Oxygen Nanocarrier Amplified Photodynamic Therapy for Eliciting Anti-tumor Immunity and Abscopal Effect

Abstract

An ideal cancer therapeutic strategy is expected to possess potent ability to not only ablate primary tumors but also prevent distance metastasis and relapse. In this study, human serum albumin was hybridized with hemoglobin by intermolecular disulfide bonds to develop a hybrid protein oxygen nanocarrier with chlorine e6 encapsulated (C@HPOC) for oxygen self-sufficient photodynamic therapy (PDT). C@HPOC realized the tumor-targeted co-delivery of photosensitizer and oxygen, which remarkably relieved tumor hypoxia. C@HPOC was favorable for more efficient PDT and enhanced infiltration of CD8 T cells in tumors. Moreover, oxygen-boosted PDT of C@HPOC induced immunogenic cell death, with the release of danger-associated molecular patterns to activate dendritic cells, T lymphocytes, and natural killer cells in vivo. Notably, C@HPOC-mediated immunogenic PDT could destroy primary tumors and effectively suppress distant tumors and lung metastasis in a metastatic triple-negative breast cancer model by evoking systemic anti-tumor immunity. This study provides a paradigm of oxygen-augmented immunogenic PDT for metastatic cancer treatment.

In Situ Photocatalyzed Oxygen Generation with Photosynthetic Bacteria to Enable Robust Immunogenic Photodynamic Therapy in Triple‐Negative Breast Cancer

“…For tumor metastasis and recurrence, it is very important to activate a systemic antitumor response and immunological memory . More recent studies have shown that local PDT can induce immunogenic cell death (ICD), which consequently induces systemic antitumor immune responses to inhibit distal tumor growth and prevent tumor reoccurrence . Compared with the currently available cancer vaccines with specific proteins or peptides as antigens for tumor immunotherapy, PDT‐mediated ICD generates vaccine‐like functions in situ and does not need foreign antigens.…”

“…Compared with the currently available cancer vaccines with specific proteins or peptides as antigens for tumor immunotherapy, PDT‐mediated ICD generates vaccine‐like functions in situ and does not need foreign antigens. However, due to the abnormal proliferation of the vascular system in solid tumor tissues, normal blood circulation cannot be formed, and solid tumors often develop a specialized hypoxic, acidic and nutrient‐deficient microenvironment, which significantly dampens the efficacy of PDT 3a,6. To achieve successful tumor therapies, previous studies have taken steps to ameliorate tumor hypoxia by increasing the oxygen concentration in tumors with tumor‐targeted oxygen‐carrying and intratumoral oxygen generation strategies 1a,7.…”

Organic Photodynamic Nanoinhibitor for Synergistic Cancer Therapy

“…[10] Fori nstance,d irect O 2 supplement using MnO 2 or perfluorocarbon (PFC) nanodroplets has been exploited to focally elevate oxygen level at tumor sites, [7] but this approach has poor temporospatial regulation of O 2 release.M oreover, efforts have been made to shift PDT from the oxygendependent type II to the H 2 O-dependent type Ipathway,but the latter often requires the use of inorganic photosensitizers containing heavy metal ions with high toxic potential. [10] Fori nstance,d irect O 2 supplement using MnO 2 or perfluorocarbon (PFC) nanodroplets has been exploited to focally elevate oxygen level at tumor sites, [7] but this approach has poor temporospatial regulation of O 2 release.M oreover, efforts have been made to shift PDT from the oxygendependent type II to the H 2 O-dependent type Ipathway,but the latter often requires the use of inorganic photosensitizers containing heavy metal ions with high toxic potential.…”

Advances of functional nanomaterials for cancer immunotherapeutic applications

“…For example, Zhikuan et al crosslinked serum albumin and oxygen‐carrying hemoglobin by disulfide bonds for carrying CE6. Under laser irradiation, ICD was induced by cytotoxic singlet molecular oxygen release, which triggered a series of immune responses (Z. Chen et al, ). There are also nanomaterials based on nucleic acid adjuvants.…”

“…Under laser irradiation, ICD was induced by cytotoxic singlet molecular oxygen release, which triggered a series of immune responses (Z. Chen et al, 2018). There are also nanomaterials based on nucleic acid adjuvants.…”