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Rapid development of nanotechnology provides promising strategies in biomedicine, especially in tumor therapy. In particular, the cellular uptake of nanosystems is not only a basic premise to realize various biomedical applications, but also a fatal factor for determining the final therapeutic effect. Thus, a systematic and comprehensive summary is necessary to overview the recent research progress on the improvement of nanosystem cellular uptake for cancer treatment. According to the process of nanosystems entering the body, they can be classified into three categories. The first segment is to enhance the accumulation and permeation of nanosystems to tumor cells through extracellular microenvironment stimulation. The second segment is to improve cellular internalization from extracellular to intracellular via active targeting. The third segment is to enhance the intracellular retention of therapeutics by subcellular localization. The major factors in the delivery can be utilized to develop multifunctional nanosystems for strengthening the tumor therapy. Ultimately, the key challenges and prospective in the emerging research frontier are thoroughly outlined. This review is expected to provide inspiring ideas, promising strategies and potential pathways for developing advanced anticancer nanosystems in clinical practice., (© 2021 Wiley-VCH GmbH.)

One of the main challenges for tumor vascular infarction in combating cancer lies in failing to produce sustained complete thrombosis. Inspired by the capability of vascular infarction in blocking the delivery of oxygen to aggravate tumor hypoxia, the performance of selective tumor thrombus inducing hypoxia activation therapy to improve the therapeutic index of coagulation-based tumor therapy is presented. By encapsulating coagulation-inducing protease thrombin and a hypoxia-activated prodrug (HAP) tirapazamine into metal-organic framework nanoparticles with a tumor-homing ligand, the obtained nanoplatform selectively activates platelet aggregation at the tumor to induce thrombosis and vascular obstruction therapy by the exposed thrombin. Meanwhile, the thrombus can cut off the blood oxygen supply and potentiate the hypoxia levels to enhance the HAP therapy. This strategy not only addresses the dissatisfaction of vascular therapy, but also conquers the dilemma of inadequate hypoxia in HAP treatment. Since clinical operations such as surgery can be used to induce coagulation, coagulation-based synergistic therapy is promising for translation into a clinical combination regimen., (© 2021 Wiley-VCH GmbH.)

The miniaturization of gold nanorods exhibits a bright prospect for intravital photoacoustic imaging (PAI) and the hollow structure possesses a better plasmonic property. Herein, miniature hollow gold nanorods (M-AuHNRs) (≈46 nm in length) possessing strong plasmonic absorbance in the second near-infrared (NIR-II) window (1000-1350 nm) are developed, which are considered as the most suitable range for the intravital PAI. The as-prepared M-AuHNRs exhibit 3.5 times stronger photoacoustic signal intensity than the large hollow Au nanorods (≈105 nm in length) at 0.2 optical density under 1064 nm laser irradiation. The in vivo biodistribution measurement shows that the accumulation in tumor of miniature nanorods is twofold as high as that of the large counterpart. After modifying with a tumor-targeting molecule and fluorochrome, in living tumor-bearing mice, the M-AuHNRs group gives a high fluorescence intensity in tumors, which is 3.6-fold that of the large ones with the same functionalization. Moreover, in the intravital PAI of living tumor-bearing mice, the M-AuHNRs generate longer-lasting and stronger photoacoustic signal than the large counterpart in the NIR-II window. Overall, this study presents the fabrication of M-AuHNRs as a promising contrast agent for intravital PAI., (© 2020 Wiley-VCH GmbH.)

An intermediate-template-directed method has been developed for the synthesis of quasi-one-dimensional Au/PtAu heterojunction nanotubes by the heterogeneous nucleation and growth of Au on Te/Pt core-shell nanostructures in aqueous solution. The synthesized porous Au/PtAu bimetallic nanotubes (PABNTs) consist of porous tubular framework and attached Au nanoparticles (AuNPs). The reaction intermediates played an important role in the preparation, which fabricated the framework and provided a localized reducing agent for the reduction of the Au and Pt precursors. The Pt7 Au PABNTs showed higher electrocatalytic activity and durability in the oxygen-reduction reaction (ORR) in 0.1 M HClO4 than porous Pt nanotubes (PtNTs) and commercially available Pt/C. The mass activity of PABNTs was 218 % that of commercial Pt/C after an accelerated durability test. This study demonstrates the potential of PABNTs as highly efficient electrocatalysts. In addition, this method provides a facile strategy for the synthesis of desirable hetero-nanostructures with controlled size and shape by utilizing an intermediate template., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)