Functional 2D Iron‐Based Nanosheets for Synergistic Immunotherapy, Phototherapy, and Chemotherapy of Tumor

Abstract

Immunotherapy efficacy has been limited by tumor-associated macrophages (TAMs), which are the most abundant immune regulatory cells infiltrating around tumor tissues. The repolarization of pro-tumor M2 TAMs to anti-tumor M1 TAMs is a very promising immunotherapeutic strategy for cancer therapy. In this manuscript, multifunctional 2D iron-based nanosheets (FeNSs) are synthesized via a simple hydrothermal method for the first time, which not only possess photothermal and photodynamic properties, but also can repolarize TAMs from M2 to M1. After modifying with polyethylene glycol and loading with bioreductive prodrug banoxantrone (AQ4N), abbreviated as AP FeNSs, it can effectively repolarize TAMs from M2 to M1 and deliver AQ4N to tumor microenvironment (TME). Moreover, the repolarized M1 TAMs overexpress inducible nitric oxide synthase, which can convert nontoxic AQ4N to cytotoxic AQ4 under hypoxic TME, enabling immunomodulation-activated chemotherapy. A series of in vitro and in vivo results corroborate that AP FeNSs effectively exert photothermal and photodynamic effects and repolarize M2 TAMs to M1 TAMs, releasing inflammatory factors and activating the chemotherapeutic effect, thereby realizing synergistic tumor therapy.

Targeting tumor-associated macrophage: an adjuvant strategy for lung cancer therapy

“…Similar design concepts have also been reported in numerous other studies, often involving the synthesis of novel co-operative immuno-photodynamic NPs carrying TAM-targeted agents conjugated with the photosensitizer. The goal of these designs is to effectively inhibit tumor growth and metastasis (212)(213)(214).…”

A bioactive nanocomposite integrated specific TAMs target and synergistic TAMs repolarization for effective cancer immunotherapy

“…Furthermore, the repolarization of TAMs may mitigate tumor-associated immunosuppression and unleash an immune response against tumor cells, eventually leading to complete tumor eradication [ 11 , 12 ]. Repolarizing TAMs to the M1 phenotype for immune recovery is an attractive tumor immunotherapeutic strategy [ 13 , 14 ]. Accordingly, TAMs are unsurprisingly linked to negative clinical outcomes in most cancers.…”

Fabricating a PDA-Liposome Dual-Film Coated Hollow Mesoporous Silica Nanoplatform for Chemo-Photothermal Synergistic Antitumor Therapy

“…More importantly, nanotechnology can enable multimodal synergistic therapies by assembling various therapeutic elements into a nanoplatform, thereby forming multifunctional nanomaterials [9][10][11]. In this regard, various synergistic nanoplatforms have been proposed, such as chemo-photothermal therapy (chemo-PTT) [12,13], chemophotodynamic therapy (chemo-PDT) [14], chemoimmunotherapy [15,16], and PTT/PDT [17].…”