Immunotherapy has emerged as one of the major strategies for cancer treatment. Unlike conventional therapeutic methods, immunotherapy can treat both primary and distant metastatic tumors through triggering systematic antitumor immune responses and can even prevent tumor recurrence after causing the formation of immune memory. However, immunotherapy still has the issues of low patient response rates and severe immune-related adverse events in clinical practices. In this regard, the combination of nanomedicine-mediated therapy with immunotherapy can modulate a tumor immunosuppressive microenvironment and thus amplify antitumor immunity. In particular, second near-infrared (NIR-II) photothermal therapy (PTT), which utilizes light conversions to generate heat for killing cancer cells, has shown unique advantages in combining with immunotherapy. In this review, the recent progress of engineering nanomedicines for NIR-II PTT combinational immunotherapy is summarized. The role of nanomedicine-mediated NIR-II PTT in inducing immunogenic cell death and reprogramming the tumor immunosuppressive microenvironment for facilitating immunotherapy are highlighted. The development of NIR-II-absorbing organic and inorganic nonmetal and inorganic metal nanomedicines for the NIR-II PTT combinational immunotherapy of cancer is also introduced in detail. Lastly, the current challenges and future perspectives of these nanomedicines for combinational immunotherapy are proposed.

permeation through the cell membrane is difficult. [10,11] Various viral-mediated transfection and nonviral transfection methods have been developed for the efficient delivery of exogenous genes into cells. [12,13] The former method generally has high transfection efficiency, while the latter method has low immunogenicity and is relatively safe. [14,15] Many cationic synthesized carriers, including polyethylenimine, dendrimers, peptides, and lipids, have been designed and used to increase the transfection efficiency of nonviral transfection. [16][17][18][19][20] In addition to gene transfection vectors and methods, the cellular microenvironment can also affect gene transfection. [21][22][23][24] Cells in tissues and organs are surrounded by neighboring cells and extracellular matrices (ECMs). [25][26][27] Cells interact with their microenvironment and neighboring cells. [28,29] Cells show different morphology depending on cell-ECM and cell-cell interactions in different tissues and organs. [30] To determine the relevance of cell morphology to cell functions, researchers have precisely controlled the cell geometry, aspect ratio, spreading area, adhesion area, and chirality of single cells by micropatterned surfaces. [31][32][33][34][35][36][37] Through the versatile micropatterning technique, cell morphology has been demonstrated to be important in controlling cell adhesion, proliferation, and stem cell differentiation. [38][39][40][41][42] The influence of cell morphology on gene transfection has also been recently reported. Large cells with a high aspect ratio and more adhesion areas are preferable for gene transfection. [43] Compared to single cells, individual cells in cell populations have a more complex microenvironment. [44] Both cell morphology and cell-cell interactions in the cell population should be considered to determine the influence of the microenvironment on cell functions. [45] Cell morphology and cell-cell interactions are dependent on cell density. [33] Therefore, cell density in the cell population can affect not only individual cell morphology but also cellcell interactions. [46] High cell density mass in pellet culture has been reported to promote chondrogenic differentiation of stem cells. [47,48] High cell density (112.5 × 10 3 cells cm −2 ) has been reported to promote chondrogenic and adipogenic differentiation of bone marrow-derived mesenchymal stem cells. [44] Cell density can also affect cell viability and gene transfection. Optimization of cell density is recommended to maximize transfection efficiency.

Abstract2D cell culture occupies an important place in cancer progression and drug discovery research. However, it limitedly models the “true biology” of tumors in vivo. 3D tumor culture systems can better mimic tumor characteristics for anticancer drug discovery but still maintain great challenges. Herein, polydopamine (PDA)‐modified decellularized lung scaffolds are designed and can serve as a functional biosystem to study tumor progression and anticancer drug screening, as well as mimic the tumor microenvironment. PDA‐modified scaffolds with strong hydrophilicity and excellent cell compatibility can promote cell growth and proliferation. After 96 h treatment with 5‐FU, cisplatin, and DOX, higher survival rates in PDA‐modified scaffolds are observed compared to nonmodified scaffolds and 2D systems. The E‐cadhesion formation, HIF‐1α‐mediated senescence decrease, and tumor stemness enhancement can drive drug resistance and antitumor drug screening of breast cancer cells. Moreover, there is a higher survival rate of CD45+/CD3+/CD4+/CD8+ T cells in PDA‐modified scaffolds for potential cancer immunotherapy drug screening. This PDA‐modified tumor bioplatform will supply some promising information for studying tumor progression, overcoming tumor resistance, and screening tumor immunotherapy drugs.

Breast cancer is considered as a worldwide disease due to the high incidence and malignant metastasis. Although numerous techniques have been developed well to conduct breast cancer therapy, the influence...