A targeting black phosphorus nanoparticle based immune cells nano-regulator for photodynamic/photothermal and photo-immunotherapy

Abstract

Photo-immunotherapy is a novel therapeutic approach against malignant tumors with minimal invasiveness. Herein, a targeting multifunctional black phosphorus (BP) nanoparticle, modified by PEGylated hyaluronic acid (HA), was designed for photothermal/photodynamic/photo-immunotherapy. In vitro and in vivo assays indicated that HA-BP nanoparticles possess excellent biocompatibility, stability, and sufficient therapeutic efficacy in the combined therapy of photothermal therapy (PTT) and photodynamic therapy (PDT) for cancer therapy. Moreover, the results of in vitro showed that HA-BP down-regulated the expression of CD206 (M2 macrophage marker) by 42.3% and up-regulated the ratio of CD86（M1 macrophage marker）by 59.6%, indicating that HA-BP nanoparticles have functions in remodeling tumor associated macrophages (TAMs) phenotype (from pro-tumor M2 TAMs to anti-tumor M1 macrophages). Fluorescence (FL) and photoacoustic (PA) multimodal imaging confirmed the selective accumulation of HA-BP in tumor site via both CD44 + mediated active targeting and passive EPR effect. In vitro and in vivo studies suggested that the combined therapy of PDT, PTT and immunotherapy using HA-BP could not only significantly inhibit original tumor but also induce immunogenic cell death (ICD) and release Damage-associated molecular patterns (DAMPs), which could induce maturation of dendritic cells (DCs) and activate effector cells that robustly evoke the antitumor immune responses for cancer treatment. This study expands the biomedical application of BP nanoparticles and displays the potential of modified BP as a multifunctional therapeutic platform for the future cancer therapy.

Black Phosphorus, an Emerging Versatile Nanoplatform for Cancer Immunotherapy

“…As a result, BP nanomaterials can serve as effective PTA for PTT [34]. Therefore, the energy of incident light can be converted to heat through BP nanomaterials, thereby leading to photothermal ablation of tumors under NIR irradiation [35]. Besides, upon illumination, the energy from the ex-Figure 1.…”

“…As a result, BP nanomaterials can serve as effective PTA for PTT [ 34 ]. Therefore, the energy of incident light can be converted to heat through BP nanomaterials, thereby leading to photothermal ablation of tumors under NIR irradiation [ 35 ]. Besides, upon illumination, the energy from the excited excitons of BP nanomaterials can be transferred to the surrounding O 2 , which subsequently leads to the change of O 2 ’s electronic configuration [ 36 ].…”

Photoactivatable nanogenerators of reactive species for cancer therapy

“…ROS can destroy tumor cells through multifactorial mechanisms, including oxidizing the biological macromolecules, destroying angiogenesis to cut off the supply of nutrients to tumor cells [ 36 , 37 ]. Typically, five therapeutic strategies including radiation therapy [ [38] , [39] , [40] , [41] ], chemodynamic therapy [ [42] , [43] , [44] , [45] , [46] ], sonodynamic therapy [ [47] , [48] , [49] , [50] ], bioreductive chemotherapeutics (e.g., tirapazamine, TPZ) [ [51] , [52] , [53] , [54] ], and photodynamic therapy (PDT) [ [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] ] can generate ROS. Among all these approaches, PDT-based cancer therapies have been extensively exploited.…”

Aggregation-induced emission luminogens for highly effective microwave dynamic therapy

“…As an alternative modality of tumor destruction, thermal ablation has been extensively explored in the clinical setting. It is considered as one of the most effective treatments in combined oncotherapy as it leads to improved tumor sensitization to PDT, chemotherapy, immunotherapy, or radiotherapy [ [10] , [11] , [12] , [13] , [14] ] because the blood flow to the tumor is enhanced through heating. When the tissues are heated, the blood vessels dilate, which increases blood flow.…”