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Natural killer (NK) cells exert cytotoxic effects against infected or stressed cells, such as tumor cells, without the limitation of major histocompatibility complex (MHC) I. NK cells secrete perforins to form tunnels to mediate the entry of granzyme into target cells. This strategy, selected by natural evolution, provides a feasible method for the delivery of antitumor drugs against intracellular targets, and avoids drug-resistant mechanisms in tumor cells, such as the pumping out of drugs mediated by multidrug resistance. We constructed pH-labile artificial NK cells (ANKC) based on nature to mediate high levels of drugs in tumor cells to overcome tumor drug resistance. Mesoporous silicon nanoparticles (MSNs) modified with benzaldehyde were designed to function as scaffolds for ANKC. Doxorubicin (Dox), a model antitumor drug, was loaded into the pores of MSNs. Melittin, a pore-forming peptide, was utilized as the gate for mesopores with an acid-labile Schiff base linkage. pH-labile ANKC released melittin and Dox in slightly acidic tumor microenvironments. Melittin, like perforin, assembled tunnels on the plasma membrane or endosome, ensuring the intracellular transportation of Dox. Dox, similar to granzyme, induced the apoptosis of tumor cells. The combinational treatment partially eased the drug resistance mechanism, such as pumping out of drugs, by continuous intracellular drug accumulation mediated by melittin pores. The pH-labile ANKC demonstrated significant Dox enrichment in drug-resistant MCF-7/Adr cells and MCF-7/Adr-based xenograft tumors in a mouse model, which eventually contributed to efficient inhibition of the proliferation and growth of MCF-7/Adr tumors. PH-labile ANKC provided a potential strategy to treat drug-resistant tumors.

The combination of stimuli-activable prodrug based chemotherapy and photodynamic therapy (PDT) has attracted increasing attention. Recent studies have verified the effectiveness of this strategy in the treatment of multiple aggressive cancers. However, in such combination, the stimuli-responsive chemotherapy and PDT have their own problems that need to be overcome. The uneven distribution of endogenous stimuli within tumor tissues makes it difficult for prodrug to be completely activated. And the inadequate tissue penetration depth of external light results in low efficiency of PDT. Aiming at these two bottlenecks, we designed a biocompatible dextran based - multi-component nanomedicine (PCL-NPs) that integrate a chemiluminescence agent luminol, a photosensitizer chlorine e6 (Ce6), and a reactive oxygen species (ROS)-activable thioketal-based paclitaxel (PTX) prodrug. The presence of overexpressed hydrogen peroxide (H2O2) inside tumor oxidizes the luminol moiety to generate in-situ light for PDT through chemiluminescence resonance energy transfer (CRET). The singlet oxygen (1O2) produced in this process not only directly kills tumor cells but also amplifies oxidative stress to accelerate the activation of PTX prodrug. We propose that the PCL-NPs have great therapeutic potential by simultaneously enhancing chemotherapy and PDT in a combination therapy.

Given the difficulties of biodegradation of mesoporous silica nanoparticles (NPs), enrichment and penetration of tumor sites, and real-time monitoring of the treatment process, we developed a kind of mannose-doping doxorubicin-loading mesoporous silica nanoparticle (MSN-Man-DOX) and coated by polydopamine-Gd3+ (PDAGd) metal-phenolic networks, as well as modified by poly (2-Ethyl-2-Oxazoline) (PEOz), constructing a novel nanomedicine MSN-Man-DOX@PDA-Gd-PEOz. Its pH-responsive charge reversal, photothermal, biodegradation, drug release, and magnetic resonance imaging (MRI) properties were evaluated in vitro. Cellular uptake, tumor penetration, lysosomal escape properties, as well as cell safety and toxicity of the nanoplatform were investigated through cell experiments. Finally, the MRI, organ distribution, photothermal condition, and comprehensive anti-tumor therapy in vivo were evaluated comprehensively through animal experiments. Research results showed that MSN-Man-DOX@PDA-Gd-PEOz had outstanding tumor enrichment and penetration abilities, which can produce excellent treatment effects through the synergistic effect of chemotherapy and photothermal therapy (PTT) with the function of magnetic resonance imaging contrast agent for disease monitoring. Besides, after finishing the therapeutic effect MSN-Man-DOX@PDA-Gd-PEOz can be biodegraded, so it had a good prospect of clinical application.

Cancer therapies based on energy conversion, such as photothermal therapy (PTT, light-to-thermal energy conversion) and photodynamic therapy (PDT, light-to-chemical energy conversion) have attracted extensive attention in preclinical research. However, the PTT-related hyperthermia damage to surrounding tissues and shallow penetration of PDT-applied light prevent further advanced clinical practices. Here, we developed a thermoelectric therapy (TET) based on thermoelectric materials constructed p-n heterojunction (SrTiO

Limited substrates content is a major hurdle dampening the antitumor effect of catalytic therapy. Herein, a two-dimensional interplanar heterojunction (FeOCl/FeOOH NSs) with ·OH generation under ultrasound irradiation is fabricated and utilized for catalytic cancer therapy. This interplanar heterojunction is prepared through replacing chlorine from iron oxychloride with hydroxyl. Benefiting from the longer hydroxyl bond length and enhanced affinity with water, the alkali replacement treatment integrates interplanar heterojunction synthesis and exfoliation in one step. In particular, a build-in electric field facilitated Z-scheme interplanar heterojunction is formed due to the aligning Fermi levels. The holes on the valence band of FeOCl have great ability to catalyze O2 evolution from H2O, meanwhile, the generated O2 is immediately and directly reduced to H2O2 by the electrons on the conductive band of FeOOH. The self-supplying H2O2 ability guarantees efficient ·OH generation via the Fenton-like reaction catalyzed by FeOCl/FeOOH NSs, which exhibits excellent anti-tumor performance.

The hypoxic tumor microenvironment is one of most major hurdles restraining the anti-tumor efficiency of photodynamic therapy (PDT). Herein, active photosynthetic Chlorophyceae (Chlorella, Chl) functionalized with black phosphorus nanosheets (BPNSs) through polyaspartic acid (PASP) and Fe

Neighboring carbon and sandwiched between non‐metals and metals in the periodic table of the elements, boron is one of the most chemically and physically versatile elements, and can be manipulated to form dimensionally low planar structures (borophene) with intriguing properties. Herein, the theoretical research and experimental developments in the synthesis of borophene, as well as its excellent properties and application in many fields, are reviewed. The decade‐long effort toward understanding the size‐dependent structures of boron clusters and the theory‐directed synthesis of borophene, including bottom‐up approaches based on different foundations, as well as up‐down approaches with different exfoliation modes, and the key factors influencing the synthetic effects, are comprehensively summarized. Owing to its excellent chemical, electronic, mechanical, and thermal properties, borophene has shown great promise in supercapacitor, battery, hydrogen‐storage, and biomedical applications. Furthermore, borophene nanoplatforms used in various biomedical applications, such as bioimaging, drug delivery, and photonic therapy, are highlighted. Finally, research progress, challenges, and perspectives for the future development of borophene in large‐scale production and other prospective applications are discussed., The successful theoretical‐research‐guided synthesis of borophene marks a milestone for the synthesis of 2D materials without layered bulk structures. The excellent properties and wide applications of borophene make it a new cousin of graphene in the family of 2D materials.

Photothermal therapy (PTT) based on the light-heat conversion principle has attracted extensive attention in preclinical research, however, the hyperthermia resulted the treatment-related damage to surrounding tissues prevents further advanced clinical practice. Here, we developed a thermoelectric therapy (TET) based on p-n heterojunction (SrTiO3/Cu2Se nanoplates) on the principle of light-heat-electricity-chemical energy conversion, demonstrating great potential for cancer treatment. The principle of TET is based on light-heat-electricity-chemical energy conversion, regarded as an upgraded version of PTT. Upon laser irradiation and subsequently natural cooling-induced the mild temperature gradient (35-45 oC), a self-build-in electric field was constructed and thereby facilated electrons and holes separation in bulk SrTiO3 and Cu2Se. Importantly, the contact between SrTiO3 (n type) and Cu2Se (p type) constructed another interficial electric field, which further guided the seperated electrons and holes to transfer to re-locate onto the surfaces of SrTiO3 and Cu2Se, respectively. The formation of two electric fields in bulk and interface of SrTiO3/Cu2Se nanoplates minimized probability of charges recombination. Of note, high-performance superoxide radicals (·O2−) and hydroxyl radicals (·OH) generation from O2 and H2O under catalization by seperated electrons and holes, led to intracellular ROS burst and cancer cells apoptosis without apparent damage to surrounding tissues. As far as it is known, this is the first report on TET based a p-n heterojunction in biomedical field. Construction of bulk and interficial electric fields in heterojunction for improving charges separation and transfer is also expected to provide a robust and universal strategy for diverse applications including energy, environment, and biomedical engineering.

Excessive reactive oxygen species (ROS), as effective cancer therapeutic agents, can promote tumor apoptosis. However, the clinical applications of ROS-mediated cancer therapies still have many limitations, such as self-defects of traditional photosensitizer, adverse tumor microenvironment (TME), and insufficient ROS production. Here, two-dimensional and highly oxidized ilmenite nanosheets (HOIL NSs, formula: FeTiO3@Fe2O3), one of perovskite analogues, were developed through combining ball-milling, probe sonication assisted liquid exfoliation, and probe sonication assisted surface oxidation. The HOIL NSs with surface oxidized Fe2O3 shell and FeTiO3 core cleverly developed a direct Z-scheme heterojunction, in which much stronger oxidation and reduction potentials in the valence band (VB) of Fe2O3 and the conduction band (CB) of FeTiO3 respectively were obtained via recombining the electrons in the CB of Fe2O3 with the holes in the VB of FeTiO3. Under irradiation of 650 nm laser, the generation of O2− from O2 and OH from OH− on the CB of FeTiO3 and VB of Fe2O3, respectively, were enhanced largely. Besides, the Fe2O3 shell and Fe3+/Fe2+ inside HOIL NSs can not only damage the TME through glutathione consumption and O2 production, but also produce OH by Fenton reaction. Moreover, the NSs can be triggered by an 808 nm laser to generate local hyperthermia for photothermal therapy. The fluorescent and photothermal imaging capabilities of the HOIL-PEG NSs also allow dual-modal imaging-guided cancer therapy.