Although notable progress has been made on novel cancer treatments, the overall survival rate and therapeutic effects are still unsatisfactory for cancer patients. Chemoimmunotherapy, combining chemotherapeutics and immunotherapeutic drugs, has emerged as a promising approach for cancer treatment, with the advantages of cooperating two kinds of treatment mechanism, reducing the dosage of the drug and enhancing therapeutic effect. Moreover, nano-based drug delivery system (NDDS) was applied to encapsulate chemotherapeutic agents and exhibited outstanding properties such as targeted delivery, tumor microenvironment response and site-specific release. Several nanocarriers have been approved in clinical cancer chemotherapy and showed significant improvement in therapeutic efficiency compared with traditional formulations, such as liposomes (Doxil®, Lipusu®), nanoparticles (Abraxane®) and micelles (Genexol-PM®). The applications of NDDS to chemoimmunotherapy would be a powerful strategy for future cancer treatment, which could greatly enhance the therapeutic efficacy, reduce the side effects and optimize the clinical outcomes of cancer patients. Herein, the current approaches of cancer immunotherapy and chemoimmunotherapy were discussed, and recent advances of NDDS applied for chemoimmunotherapy were further reviewed.

Immune checkpoint therapy promotes cytotoxic T lymphocytes (CTLs) activity to eliminate tumors. Nevertheless, their effectiveness in solid tumors is limited by inadequate infiltration of CTLs and suppressive tumor microenvironment (TME). Herein, an anti‐PD‐1 antibody coupled chemo‐photothermal integrated nanoplatform (A/Au@MSMs‐P) is proposed to reshape antitumor immunity against cancer. The matrix metalloproteinase‐2 (MMP‐2) responsive A/Au@MSMs‐P promotes the separation of abemaciclib‐loaded gold‐silica nanoparticles (A/Au@MSMs) and anti‐PD‐1 antibody, achieving a triple‐coordinated strategy to enhance checkpoint blockade therapy. First, chemo‐photothermal therapy of A/Au@MSMs induces cell cycle arrest in G1 phase and promotes tumor cells apoptosis to achieve local ablation. Second, immunogenic death of tumor cells promotes the maturation of dendritic cells and recruits antigen‐specific CTLs into tumor tissue to promote immune activation. Third, abemaciclib markedly suppresses the proliferation of regulatory T cells (Tregs) to alleviate the immunosuppression of the TME and potentiates the effectiveness of CTLs. This triple‐coordinated strategy not only reshapes the antitumor immunity to enhance checkpoint blockade, but also cooperates with chemo‐photothermal therapy, leading to improved antitumor efficiency and prolonged survival rate. Taken together, this study presents a promising strategy for improving checkpoint therapy response and has great potential in future cancer therapy.

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Eliminating primary tumor (“roots”) and inhibiting associated‐circulating tumor cells (associated‐CTCs, “seeds”) are vital issues that need to be urgently addressed in cancer therapy. Associated‐CTCs, which include single CTCs, CTC clusters, and CTC–neutrophil clusters, are essential executors in metastasis and the cause of metastasis‐related death in cancer patients. Herein, a “roots and seeds” multipoint costriking nanodevice (GV‐Lipo/sorafenib (SF)/digitoxin (DT)) is developed to eliminate primary tumors and inhibit the spread of associated‐CTCs for enhancing metastasis inhibition and the therapeutic effect on hepatocellular carcinoma (HCC). GV‐Lipo/SF/DT eliminates primary tumor cells by the action of SF, thus reducing CTC production at the roots and improving the therapeutic effect on HCC. GV‐Lipo/SF/DT inhibits associated‐CTCs effectively via the enhanced identification and capture effects of glypican‐3 and/or vascular cell adhesion molecule 1 (VCAM1) targeting, dissociating CTC clusters using DT, blocking the formation of CTC–neutrophil clusters using anti‐VCAM1 monoclonal antibody, and killing CTCs with SF. It is successfully verified that GV‐Lipo/SF/DT increases the CTC elimination efficiency in vivo, thus effectively preventing metastasis, and shows enhanced antitumor efficacy in both an H22‐bearing tumor model and orthotopic HCC models. Overall, the “roots and seeds” multipoint costriking strategy may open a new cancer treatment model for the clinic.

In recent years, therapeutic strategies based on macrophages have been inspiringly developed, but due to the high intricacy and immunosuppression of the tumor microenvironment, the widespread use of these strategies still faces significant challenges. Herein, an artificial assembled macrophage concept (AB@LM) was presented to imitate the main antitumor abilities of macrophages of tumor targeting, promoting the antitumor immunity, and direct tumor-killing effects. The artificial assembled macrophage (AB@LM) was prepared through an extrusion method, which is to fuse the macrophage membrane with abemaciclib and black phosphorus quantum dot (BPQD)-loaded liposomes. AB@LM showed good stability and tumor targeting ability with the help of macrophage membrane. Furthermore, AB@LM reversed the immunosuppressive tumor microenvironment by inhibiting regulatory T cells (Tregs) and stimulating the maturation of antigen-presenting cells to activate the antitumor immune response through triggering an immunogenic cell death effect. More importantly, in the colorectal tumor model in vivo, a strong cooperative therapeutic effect of photo/chemo/immunotherapy was observed with high tumor inhibition rate (95.3 ± 2.05%). In conclusion, AB@LM exhibits excellent antitumor efficacy by intelligently mimicking the abilities of macrophages. A promising therapeutic strategy for tumor treatment based on imitating macrophages was provided in this study.