Recently, diverse functional materials that take subcellular structures as therapeutic targets are playing increasingly important roles in cancer therapy. Here, particular emphasis is placed on four ...kinds of therapies, including chemotherapy, gene therapy, photodynamic therapy (PDT), and hyperthermal therapy, which are the most widely used approaches for killing cancer cells by the specific destruction of subcellular organelles. Moreover, some non‐drug‐loaded nanoformulations (i.e., metal nanoparticles and molecular self‐assemblies) with a fatal effect on cells by influencing the subcellular functions without the use of any drug molecules are also included. According to the basic principles and unique performances of each treatment, appropriate strategies are developed to meet task‐specific applications by integrating specific materials, ligands, as well as methods. In addition, the combination of two or more therapies based on multifunctional nanostructures, which either directly target specific subcellular organelles or release organelle‐targeted therapeutics, is also introduced with the intent of superadditive therapeutic effects. Finally, the related challenges of critical re‐evaluation of this emerging field are presented.
The rapid development in the field of subcellular targeted cancer therapy is reviewed systemically and comprehensively on account of six sets of treatment modalities: chemotherapy, gene therapy, PDT, hyperthermia, non‐drug‐loaded nanoformulations, and synergistic combined therapy.
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Immunotherapy that can activate immunity or enhance the immunogenicity of tumors has emerged as one of the most effective methods for cancer therapy. Nevertheless, single‐mode immunotherapy is still ...confronted with several critical challenges, such as the low immune response, the low tumor infiltration, and the complex immunosuppression tumor microenvironment. Recently, the combination of immunotherapy with other therapeutic modalities has emerged as a powerful strategy to augment the therapeutic outcome in fighting against cancer. In this review, recent research advances of the combination of immunotherapy with chemotherapy, phototherapy, radiotherapy, sonodynamic therapy, metabolic therapy, and microwave thermotherapy are summarized. Critical challenges and future research direction of immunotherapy‐based cancer therapeutic strategy are also discussed.
Immunotherapy‐involved combination cancer therapy: the rapid development in the combination of immunotherapy with other therapeutic modalities for cancer therapy are systematically reviewed, and the critical challenges and future directions are also discussed.
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Cell primitive-based functional materials that combine the advantages of natural substances and nanotechnology have emerged as attractive therapeutic agents for cancer therapy. Cell primitives are ...characterized by distinctive biological functions, such as long-term circulation, tumor specific targeting, immune modulation
etc.
Moreover, synthetic nanomaterials featuring unique physical/chemical properties have been widely used as effective drug delivery vehicles or anticancer agents to treat cancer. The combination of these two kinds of materials will catalyze the generation of innovative biomaterials with multiple functions, high biocompatibility and negligible immunogenicity for precise cancer therapy. In this review, we summarize the most recent advances in the development of cell primitive-based functional materials for cancer therapy. Different cell primitives, including bacteria, phages, cells, cell membranes, and other bioactive substances are introduced with their unique bioactive functions, and strategies in combining with synthetic materials, especially nanoparticulate systems, for the construction of function-enhanced biomaterials are also summarized. Furthermore, foreseeable challenges and future perspectives are also included for the future research direction in this field.
This review provides a comprehensive understanding of the combination of cell primitives and synthetic materials for constructing function-enhanced hybrid materials in the fight against cancer.
This paper presents an airborne piezoelectric micromachined ultrasonic transducers (PMUTs) operated at low frequency (40-50 kHz) for long-range detection, where the acoustic absorption loss in air is ...relatively low (0.8-1 dB/m). The PMUTs made with single-crystal Lead Zirconate Titanate (PZT) enables a high piezoelectric coefficient (<inline-formula> <tex-math notation="LaTeX">{e} _{31, f} \approx ~16 </tex-math></inline-formula>- 24 C/<inline-formula> <tex-math notation="LaTeX">\text{m}^{{2}} </tex-math></inline-formula>), and a low dielectric constant (<inline-formula> <tex-math notation="LaTeX">\varepsilon _{\mathrm {r}}~\approx ~308 </tex-math></inline-formula>), achieving high PMUT transceiver efficiency. The <inline-formula> <tex-math notation="LaTeX">2\times 2 </tex-math></inline-formula> PMUT array achieves a very high sound pressure level (SPL) output of 109.4 dB at 26 cm distance. Different from conventional PZT PMUTs, this study utilized single-crystal PZT with a low permittivity to achieve a good acoustic reception, demonstrating the sensitivity of 2 mV/Pa. This work reports the PMUT design, modeling, fabrication, characterization, enabling a long-range detection of 4.8 meters in a pulse-echo experiment, which was conducted by a pair of <inline-formula> <tex-math notation="LaTeX">2\times 2 </tex-math></inline-formula> PMUT arrays with the matched resonances. 2020-0270
Poor tumor selectivity and short life span of reactive oxygen species (ROS) are two major challenges in photodynamic therapy (PDT). In this study, a self‐transformable pH‐driven membrane anchoring ...photosensitizer (pHMAPS) is used to realize tumor‐specific accumulation and in situ PDT on tumor cell membrane to maximize the therapeutic potency. It is found that pHMAPS was able to form α‐helix structure under acidic condition (pH 6.5 or 5.5), while remain random coil at normal pH of 7.4. This pH‐driven secondary structure switch enables the successful insertion of pHMAPS into membrane lipid bilayer, especially for cancerous cell membrane in the acidic tumor microenvironment. Under laser irradiation, cytotoxic ROS is generated in the immediate vicinity of cell membrane, resulting in superior cell killing effect in vitro and significant inhibition of tumor growth in vivo. Importantly, benefited from this membrane‐specific PDT, tumor growth‐induced hepatic, pulmonary, as well as osseous metastases of breast cancer cells are also retarded after PDT treatment. Thus, the membrane localized PDT by pHMAPS provides a simple but effective strategy to enhance the medical performance of photosensitizing agents in cancer therapy.
Membrane‐anchoring photodynamic therapy: A pH‐driven membrane‐anchoring photodynamic therapy is developed to inhibit tumor growth and metastasis. With the formation of α‐helix structure in tumor acidic microenvironment, pH‐driven membrane anchoring photosensitizer can rapidly insert into tumor cell membrane and the membrane localized photodynamic therapy (PDT) directly induces significant membrane damage, giving rise to superior cell killing effect and enhanced PDT.
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Nucleic acid–modified UiO‐68 metal–organic framework nanoparticles, NMOFs, are loaded with the anticancer drug camptothecin (or drug models), and the loaded NMOFs are capped with sequence‐specific ...duplex units. The NMOFs are unlocked by the biocatalytic decomposition of the duplex capping units that result in the release of the drug (or drug models). The enzymes used are DNase I, a nicking enzyme (Nt.BbvCI), an endonuclease (EcoRI), and an exonuclease III (Exo III). Camptothecin‐loaded NMOFs, capped by tailored hairpin nucleic acids being cooperatively unlocked by adenosine triphosphate (ATP), that is overexpressed in cancer cells, and Exo III are prepared. The camptothecin‐loaded NMOFs reveal that selective cytotoxicity toward MDA‐MB‐231 cancer cells and ≈55% apoptosis of the cancer cells is observed after 5 days of treatment with the NMOFs, while only ≈15% apoptosis of epithelial MCF‐10A breast cells is observed.
Nucleic acid–capped drug‐loaded metal–organic framework nanoparticles (NMOFs) are unlocked by the biocatalytic degradation of the nucleic acid capping units, resulting in the release of the drug. By the capping of drug‐loaded NMOFs with hairpin units that include adenosine triphosphate (ATP)–aptamer sequences, the unlocking of the capping units, in the presence of ATP, proceeds. The drug‐loaded NMOFs reveal selective cytotoxicity toward MDA‐MB‐231 cancer cells.
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Zeolitic Zn2+-imidazolate cross-linked framework nanoparticles, ZIF-8 NMOFs, are used as “smart” glucose-responsive carriers for the controlled release of drugs. The ZIF-8 NMOFs are loaded with the ...respective drug and glucose oxidase (GOx), and the GOx-mediated aerobic oxidation of glucose yields gluconic acid and H2O2. The acidification of the NMOFs’ microenvironment leads to the degradation of the nanoparticles and the release of the loaded drugs. In one sense-and-treat system, GOx and insulin are loaded in the NMOFs. In the presence of glucose, the nanoparticles are unlocked, resulting in the release of insulin. The release of insulin is controlled by the concentration of glucose. In the second sense-and-treat system, the NMOFs are loaded with the antivascular endothelial growth factor aptamer (VEGF aptamer) and GOx. In the presence of glucose, the ZIF-8 NMOFs are degraded, leading to the release of the VEGF aptamer, which acts as a potential inhibitor of the angiogenetic regeneration of blood vessels by VEGF. As calcination of the VEGF-generated blood vessels leads to blindness of diabetic patients, the functional NMOFs might act as “smart” materials for the treatment of macular diseases. The potential cytotoxicity of the NMOFs originated from the GOx-generated H2O2 is resolved by the co-immobilization of the H2O2-scavanger catalase in the NMOFs.
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UiO‐68 metal–organic framework nanoparticles (NMOFs) are loaded with a doxorubicin drug (fluorescent dye analogs) and locked by means of structurally engineered duplex nucleic acid structures, where ...one strand is covalently linked to the NMOFs and the second strand is hybridized with the anchor strand. Besides the complementarity of the second strand to the anchor sequence, it includes the complementary sequence to the microRNAs (miRNA)‐21 or miRNA‐221 that is specific miRNA biomarker for MCF‐7 breast cancer cells or OVCAR‐3 ovarian cancer cells. In the presence of the respective miRNA biomarkers, the miRNA‐induced displacement of the strand associated with the anchor strand proceeds, resulting in the release of DNA/miRNA duplexes. The released duplexes are, however, engineered to be digested in the presence of exonuclease III, Exo III, a process that recycles the miRNAs and provides the autonomous amplified unlocking of the NMOFs and the release of the doxorubicin load (or the fluorescent dye analogs) even at low concentrations of miRNA. Preliminary cell experiments reveal that the respective NMOFs are unlocked by the miRNA‐21 or miRNA‐221, resulting in selective cytotoxicity toward MCF‐7 breast cancer cells or OVCAR‐3 ovarian cancer cells.
miRNA‐responsive NMOFs: UiO‐68 metal–organic framework nanoparticles are loaded with doxorubicin and gated with specific miRNA‐responsive nucleic acid locks. In the presence of miRNA‐21 (a breast cancer biomarker) or miRNA‐221 (an ovarian cancer biomarker), the gates are unlocked, leading to the release of the drug. Selective cytotoxicity toward respective cancer cells is demonstrated.
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Significance Whether infinitely fast spinning vortices can develop in initially smooth, incompressible inviscid flow fields in finite time is one of the most challenging problems in fluid dynamics. ...Besides being a difficult mathematical question that has remained open for more than 250 years, the problem also attracts great attention in the physics and engineering communities due to its potential connection to the onset of turbulence in viscous flows. This paper attempts to provide an affirmative answer to this long-standing open question from a numerical point of view, by describing a class of rotationally symmetric flows from which infinitely fast spinning vortices can form in finite time. It suggests, after decades of controversies, a promising direction to the resolution of the problem.
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In this study, we report on a redox-controllable and reversible complete “ON”/“OFF”-switchable aptamer binding to ATP. A series of methylene blue-modified ATP–aptamers was synthesized, revealing ...improved binding affinities toward ATP as compared to the nonmodified aptamer. These binding affinities were dependent on the conjugation site of the redox label on the aptamer scaffold. Importantly, we find that the oxidized methylene blue-modified aptamers bind to ATP with micromolar affinity, while the reduced form lacks binding affinity toward ATP, resulting in an unprecedented complete “ON”/“OFF” redox-controllable aptamer switch. We demonstrate the cyclic “ON”/“OFF” binding of ATP to the methylene blue-functionalized aptamer through cyclic oxidation and reduction of the redox label using both chemical and electrochemical means. Molecular dynamics and docking simulations were performed to account for the redox-switchable properties of the conjugated aptamers and to rationalize the enhanced binding affinities of the different aptamer designs.
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