Synergistic Effect of Photothermally Targeted NIR-Responsive Nanomedicine-Induced Immunogenic Cell Death for Effective Triple Negative Breast Cancer Therapy

Abstract

Triple negative breast cancer (TNBC) is a breast cancer subtype. At present, TNBC patients do not have approved targeted therapy. Therefore, patients primarily depend on forceful systemic chemotherapy that has unavoidable harmful side effects, resulting in inadequate therapeutic outcomes and leading to a high mortality rate. Hence, there is an urgent need to develop targeted therapies for the TNBC populace. Developing a new nanotherapeutic approach of combinational therapy could be an effective alternative strategy. Therefore, we designed a combination of hyaluronan (HA)–polyaniline (PANi)–imiquimod (R837), denoted as HA-PANi/R837, nanoparticles (NPs) that exhibited a high extinction coefficient of 8.23 × 108 M–1 cm–1 and adequate photothermal conversion efficiency (PCE) (η = 41.6%), making them an efficient photothermal agent (PTA) that is highly beneficial for selective CD44-mediated photothermal ablation of TNBC tumors. Furthermore, co-encapsulation of R837 (toll-like receptor 7 agonist) immunoadjuvant molecules triggers an immune response against the tumor. The formed CD44-targeted HA-PANi/R837 NPs’ selectivity incinerates the tumor under near-infrared (NIR)-triggered photothermal ablation, generating tumor-associated antigens and triggering R837 combination with anti-CTLA-4 for immunogenic cell death (ICD) activation to kill the remaining tumor cells in mice and protect against tumor relapse and metastasis. Our results demonstrated that novel HA-PANi/R837 NP-induced photothermal ICD achieved in CD44-targeted TNBC is a promising application.

Immunotherapy for Triple-Negative Breast Cancer

“…An excellent PAT is characterized by strong light absorption, strong photothermal conversion ability, stability, good biocompatibility, and the ability to turn off PTT in the non-treatment stage [92]. Near-infrared PAT include polyaniline [93], copper sulfides (CuS) NPs [94], as well as inorganic NPs, such as gold-based NPs [95]. Inorganic NPs show high photothermal conversion efficiency but relatively poor biocompatibility and toxicity [95], while liposome-based material and organic-conjugated polymers exhibit relatively better biocompatibility [96].…”

“…To specifically target CD44, Yasothamani et al [93] designed a conjugation of hyaluronan (HA)−polyaniline (PANi)−imiquimod (R837), denoted as HA-PANi/R837. The high photothermal conversion efficiency of PANi means that it has a significant thermal ablation effect in solid tumor.…”

Targeted NIR-responsive theranostic immuno-nanomedicine combined TLR7 agonist with immune checkpoint blockade for effective cancer photothermal immunotherapy

“…These results demonstrated that photothermal cancer therapy combined with immunotherapy developed the anticancer killing effect. PANi NPs showed good biocompatibility so that after the PTT treatment no significant changes in mice body weight was observed in any of the groups, indicating that the toxicity of the treatment was not obvious 32 (Fig. 3c).…”

Ultrasound and laser-promoted dual-gas nano-generator for combined photothermal and immune tumor therapy

“…Another report showed that the sudden burst CO 2 bubbles in the tumor microenvironment can also stimulate efficient immunogenicity by inducing membrane rupture of cancer cells ( Jeon et al, 2022 ). Several studies have demonstrated that PTT can not only directly destroy tumor cells but also indirectly stimulate systemic immunity ( Jiao et al, 2021 ; Yasothamani et al, 2021 ); therefore, the combined treatment using PTT and an ICD-inducer is anticipated to improve the efficiency of immunotherapy. Nevertheless, the hypoxic characteristics of tumors impair the efficiency of PTT and immunotherapy.…”