Macrophage-mimic shape changeable nanomedicine retained in tumor for multimodal therapy of breast cancer

The current nanomedicines for cancer therapy based on the enhance permeability and retention (EPR) effect remain insufficient to satisfy the clinical need, and the challenges hindering nanomedicines delivery should be conquered for strong therapeutic efficacy. To address these problems, a membrane-coated laser-responsive shape changeable nanomedicine, I-P@NPs@M, is reported. The covering macrophage membrane promotes the circulation and tumor targeting of nanomedicines. Then the chlorin e6 (Ce6) in I-P@NPs@M can convert 650 nm laser into reactive oxygen species (ROS) to trigger the spherical micelles changing into nanofibers for strong retention in tumor region, consequently the linear nanofibers long locate and sustainably release drugs. On the other hand, the ROS not only directly kills tumor cells by photodynamic therapy but stimulates the dimeric paclitaxel (PTX) generating monomeric PTX. The combinational chemo- photodynamic therapy heavily suppresses tumor growth and inducing immunogenic cell death, which is synergistic with Indoximod (IND) inhibiting the IDO pathway to activate immune response for immunotherapy. By chemotherapy, photodynamic therapy and immunotherapy gathering, the treatment of I-P@NPs@M + laser shows the best antitumor effect, resulting in 85.27 ± 12.80% suppression of breast cancer in mice model, and also remarkably inhibits lung metastasis. The macrophage membrane-coated shape changeable nanomedicine, I-P@NPs@M, successively overcomes the challenges of blood circulation, tumor targeting, intratumoral distribution, cellular internalization and drug release, fulfilling multimodal therapy by specific and effective chemotherapy, photodynamic therapy and immunotherapy, which strongly suppress the growth of breast cancer tumor and inhibit lung metastasis on the mice model. [Display omitted] •Successively overcome the barriers lying on the drug delivery to breast cancer tumor.•Combine membrane coating and shape change for enhancing biodistribution.•Utilize dimeric drugs for the good loading and specific drug activities.•Conjugate the multimodal therapy in order for strong efficacy.