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.

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Theranostic nanoparticles (TNPs) is an efficient avenue that culminates both diagnosis and therapy into cancer treatment. Herein, we have formulated a theranostic nanocomposite (NC) with CuS being the ultra-small core component. To ensure stability to the NC, PEI was added which is a vital anchoring group polymer, especially on sulfide surfaces, and adds quality by being a better stabilizer and reducing agent. Additionally, to add stability, specificity, and added photothermal efficiency to the fabricated NC. In addition, encapsulation of indocyanine green (ICG), an efficient NIR absorber, and Folic acid (FA) were conjugated systematically, characterized, and analyzed for photo-stability. The photothermal conversion efficiency of the novel NC (CuS-PEI-ICG-FA) was analyzed at 808 nm, where the NC efficiently converted light energy to heat energy. The NC was also tested for hemocompatibility to clarify and also determined biocompatibility. Surprisingly, damage-associated molecular patterns (DAMPs) from post-PTT of tumor cells activate immunogenic cell death (ICD) for tumor-specific immune responses. The deserving photothermal performance and photo-stability makes the NC an ideal platform for photoacoustic imaging (PAI). A superior contrast was observed for PAI in a concentration-dependent manner enhancing the level of penetration into tissues, thereby better imaging. On account of this study, the newly formulated NC could be utilized as a "nanotheranostic" designed for therapeutic and image diagnostic agent of cancer biomedical applications.

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Integrated tumor-seeking nanomedicine (TSN) is designed to achieve a high therapeutic anticancer effect that is highly desirable for effective cancer treatment to overcome the detrimental effects of conventional therapies. However, direct administration of drugs cannot achieve a high level of specificity, which remains a formidable challenge. To address the confines, incorporation of multifunctionalities to maximize the specificity of TSN must be performed; TSN picks up multiple cargoes that are initially arrested at the core location and delivers each type simultaneously to a specified destination. Here, we introduce a valuable approach of Her2/neu-rich tumor cell surface-receptor-targeting TSN, which was highly pH-responsive and significantly realized the selective triple-therapeutic effects of blocking Her2/neu functions, chemotherapy, and phototherapy (photodynamic therapy (PDT)/ photothermal therapy (PTT)). Therefore, the unprecedented selectivity of TSN provides a triple-therapeutic effect to spread the repertoire of "TSN" targets for future clinically relevant translation in improving breast cancer therapy.