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.