Cancer immunotherapy has veered the paradigm of cancer treatment. Despite recent advances in immunotherapy for improved antitumor efficacy, the complicated tumor microenvironment (TME) is highly immunosuppressive, yielding both astounding and unsatisfactory clinical successes. In this regard, clinical outcomes of currently available immunotherapy are confined to the varied immune systems owing in large part to the lack of understanding of the complexity and diversity of the immune context of the TME. Various advanced designs of nanomedicines could still not fully surmount the delivery barriers of the TME. The immunosuppressive TME may even dampen the efficacy of antitumor immunity. Recently, some nanotechnology-related strategies have been inaugurated to modulate the immunosuppressive cells within the tumor immune microenvironment (TIME) for robust immunotherapeutic responses. In this review, we will highlight the current understanding of the immunosuppressive TIME and identify disparate subclasses of TIME that possess an impact on immunotherapy, especially those unique classes associated with the immunosuppressive effect. The immunoregulatory cell types inside the immunosuppressive TIME will be delineated along with the existing and potential approaches for immunosuppressive cell modulation. After introducing the various strategies, we will ultimately outline both the novel therapeutic targets and the potential issues that affect the efficacy of TIME-based nanomedicines.

In tumor therapy, nanodrug delivery systems have gained momentum in the last decade. However, its efficacy remains insufficient for clinical applications. The physical properties of nanoparticles, including size, shape, and surface characteristics, can strongly affect the delivery efficacy. Ironically, research on shape function is relatively scarce, although the nanoparticle shape greatly impacts their performance; for example, nanorods with a high aspect ratio (AR) achieve greater accumulation, but their penetration is relatively weak. Hence, rather than selecting a suitable AR to balance them, the strategy of a transformable AR (i.e., transformation) is ideal in this case. Nanoparticle transformation can be achieved by either internal stimuli (such as pH and enzymes) or external stimuli (such as light) spatially and temporally with precision, thereby dramatically enhancing the efficiency of drug delivery. Thus, nanoparticle transformation is becoming a promising prospect for improving cancer treatment. In this review, first, the effect of shape on drug delivery is summarized, then, the recently transformable drug delivery systems are reviewed, and finally, the future direction of shape‐transformable nanoparticles in tumor therapy is discussed.

Accurate tumor targeting, deep penetration and superb retention are still the main pursuit of developing excellent nanomedicine. To achieve these requirements, a stepwise stimuli-responsive strategy was developed through co-administration tumor penetration peptide iRGD with shape-transformable and GSH-responsive SN38-dimer (d-SN38)-loaded nanoparticles (d-SN38@NPs/iRGD). Upon intravenous injection, d-SN38@NPs with high drug loading efficiency (33.92 ± 1.33%) could effectively accumulate and penetrate into the deep region of tumor sites with the assistance of iRGD. The gathered nanoparticles simultaneously transformed into nanofibers upon 650 nm laser irradiation at tumor sites so as to promote their retention in the tumor and burst release of reactive oxygen species for photodynamic therapy. The loaded d-SN38 with disulfide bond responded to the high level of GSH in tumor cytoplasm, which consequently resulted in SN38 release and excellent chemo-photodynamic effect on tumor. In vitro, co-administering iRGD with d-SN38@NPs+laser showed higher cellular uptake, apoptosis ratio and multicellular spheroid penetration. In vivo, d-SN38@NPs/iRGD+laser displayed advanced penetration and accumulation in tumor, leading to 60.89% of tumor suppression in 4T1 tumor-bearing mouse model with a favorable toxicity profile. Our new strategy combining iRGD with structural transformable nanoparticles greatly improves tumor targeting, penetrating and retention, and empowers anticancer efficacy.

Constructing graphene-based heterostructures with large interfacial area is an efficient approach to enhance the electrochemical performance of supercapacitors but remains great challenges in their synthesis. Herein, a novel ultra-small amorphous Fe₂O₃ nanodots/graphene heterostructure (a-Fe₂O₃ NDs/RGO) aerogel was facilely synthesized via excessive metal-ion-induced self-assembly and subsequent calcination route using Prussian blue/graphene oxide (PB/GO) composite aerogel as precursors. The deliberately designed a-Fe₂O₃ NDs/RGO heterostructure offers a highly interconnected porous conductive network, large heterostructure interfacial area, and plenty of accessible active sites, greatly facilitating the electron transfer, electrolyte diffusion, and pseudocapacitive reactions. The obtained a-Fe₂O₃ NDs/RGO aerogel could be used as flexible free-standing electrodes after mechanical compression, which exhibited a significantly enhanced specific capacitance of 347.4 F·g⁻¹ at 1 A·g⁻¹, extraordinary rate capability of 184 F·g⁻¹ at 10 A·g⁻¹, and decent cycling stability. With the as-prepared a-Fe₂O₃ NDs/RGO as negative electrodes and the Co₃O₄ NDs/RGO as positive electrodes, an all-solid-state asymmetric supercapacitor (a-Fe₂O₃ NDs/RGO//Co₃O₄ NDs/RGO asymmetric supercapacitor (ASC)) was assembled, which delivered a high specific capacitance of 69.1 F·g⁻¹ at 1 A·g⁻¹ and an impressive energy density of 21.6 W·h·kg⁻¹ at 750 W·kg⁻¹, as well as good cycling stability with a capacity retention of 94.3% after 5,000 cycles. This work provides a promising avenue to design high-performance graphene-based composite electrodes and profound inspiration for developing advanced flexible energy-storage devices.