Catalase-positive Staphylococcus epidermidis based cryo-millineedle platform facilitates the photo-immunotherapy against colorectal cancer via hypoxia improvement.

The synergistic anti-tumor impact of phototherapy and a cascading immune response are profoundly limited by hypoxia and a weakened immune response. Intravenous and intratumoral injection of therapeutic drugs also cause pain, rapid drug clearance and low utilization rates. Here, a novel cryo-millineedle platform for intratumoral delivery of a phototherapy system, S.epi@IR820, is developed in this work, combining the properties of Staphylococcus epidermidis (S. epidermidis) and IR820 for photo-immunotherapy of colorectal cancer. In this cryo-millineedle platform, S. epidermidis enhances the near-infrared absorption and light stability of IR820 and catalyzes the decomposition of H2O2 into O2 via an endogenous catalase to relieve tumor hypoxia, improve phototherapy and enhance immunogenic cell death (ICD). More interestingly, the native immunogenicity of S. epidermidis and ICD elicited by phototherapy achieved a potent anti-tumor immune response. To the best of our knowledge, this is the first study to utilize native S. epidermidis to relieve hypoxia and facilitate phototherapy. Both in vitro and in vivo experiments showed that the millineedle based phototherapy system can efficiently catalyse the decomposition of H2O2 into O2, facilitate phototherapeutic killing of CT26 tumor cells by S.epi@IR820 and enhance ICD, thus successfully activated the immune response and achieved the photo-immunotherapy against colorectal cancer. In conclusion, this study provides a novel strategy for enhanced anti-tumor efficiency of photo-immunotherapy, and develops an effective method for orthotopic administration of tumors.

Platelet membrane-based biochemotactic-targeting nanoplatform combining PDT with EGFR inhibition therapy for the treatment of breast cancer.

Presently, the commonly used anti-tumor drugs lack targeting ability, resulting in a limited therapeutic efficacy and significant side effects. In this view, platelet membranes (PMs) not only exhibit specific binding of its P-selectin protein with CD44, which is highly expressed on breast cancer cells, to promote tumor-active targeting by PM biomimetic nanoplatforms, but also respond to vascular damage, thus inducing biochemotactic targeting to further facilitate the aggregation of these nanoplatforms. Therefore, in this study, a PM was applied to construct a biochemotactic-targeting nanotherapeutic platform based on dendritic large pore mesoporous silica nanoparticles (DLMSNs) co-loaded with chlorin e6 (Ce6) and lapatinib (LAP) to achieve the combination of photodynamic therapy (PDT) and EGFR inhibition therapy for breast cancer. Under laser irradiation, PM@DLMSN/Ce6/Lap could not only effectively kill breast tumor cells by the PDT, but also damage blood vessels. By combining the EGFR inhibition of LAP, PM@DLMSN/Ce6/Lap could better inhibit the migration and movement of tumor cells. In vitro and in vivo results showed that PM@DLMSN/Ce6/Lap could achieve active-targeting drug delivery to breast tumors and further recruit more nanoparticles to accumulate at tumor sites after the PDT-induced damage of blood vessels through biochemotactic targeting, achieving continuous EGFR inhibition to prevent tumor proliferation and metastasis. In conclusion, this study not only provides a new strategy for the clinical treatment of breast cancer, but also provides a design idea for improving the targeted delivery of anti-tumor drugs.

Endoplasmic reticulum-targeted NIR-II phototherapy combined with inflammatory vascular suppression elicits a synergistic effect against TNBC.

Recurrence and metastasis are the main reasons for failure in the treatment of triple-negative breast cancer (TNBC). Phototherapy, one of the most well-known potent cancer treatment models is highlighted by ablating primitive tumors with immunogenic cell death (ICD) and is associated with endoplasmic reticulum (ER) stress to elicit long-lasting anti-tumor immunity. However, the provoked inflammatory response after phototherapy will stimulate angiogenesis, which provides nutrition for tumor recurrence. Here, an ER-targeted nanoplatform was constructed based on hollow mesoporous Cu2-XS (HMCu2-XS) nanoparticles to suppress recurrence and metastasis of TNBC by combining photo-ablation and microenvironment remodeling. Profiting from the metal ion coordination and large hollow space, HMCu2-XS can be easily modified with p-toluenesulfonamide for ER-targeting and quantitatively loaded celecoxib (CXB) as a vascular inhibitor, thus obtaining ER-HMCu2-XS/CXB. ER-HMCu2-XS showed great photothermal and photodynamic efficiency for ablating 4T1 tumors and inducing ICD under NIR-II laser irradiation. Compared with non-ER-targeted nanosystems, the ER-targeted nanosystem elicited stronger ICDs and recruited more immune cells. Moreover, the thermal-responsively released CXB successfully inhibited angiogenesis after photothermal therapy. The data showed that the ER-HMCu2-XS/CXB mediated the triplicate therapeutic effect of photo-ablation, immune response activation, and vascular suppression effectively, preventing the recurrence and metastasis of TNBC. In conclusion, this work provides a synergistic strategy to enhance therapeutic outcomes in TNBC.