Search

Background: In comparison with traditional therapeutics, it is highly preferable to develop a combinatorial therapeutic modality for nanomedicine and photothermal hyperthermia to achieve safe, efficient, and localized delivery of chemotherapeutic drugs into tumor tissues and exert tumor-activated nanotherapy. Biocompatible organic-inorganic hybrid hollow mesoporous organosilica nanoparticles (HMONs) have shown high performance in molecular imaging and drug delivery as compared to other inorganic nanosystems. Disulfiram (DSF), an alcohol-abuse drug, can act as a chemotherapeutic agent according to its recently reported effectiveness for cancer chemotherapy, whose activity strongly depends on copper ions., Results: In this work, a therapeutic construction with high biosafety and efficiency was proposed and developed for synergistic tumor-activated and photothermal-augmented chemotherapy in breast tumor eradication both in vitro and in vivo. The proposed strategy is based on the employment of HMONs to integrate ultrasmall photothermal CuS particles onto the surface of the organosilica and the molecular drug DSF inside the mesopores and hollow interior. The ultrasmall CuS acted as both photothermal agent under near-infrared (NIR) irradiation for photonic tumor hyperthermia and Cu 2+ self-supplier in an acidic tumor microenvironment to activate the nontoxic DSF drug into a highly toxic diethyldithiocarbamate (DTC)-copper complex for enhanced DSF chemotherapy, which effectively achieved a remarkable synergistic in-situ anticancer outcome with minimal side effects., Conclusion: This work provides a representative paradigm on the engineering of combinatorial therapeutic nanomedicine with both exogenous response for photonic tumor ablation and endogenous tumor microenvironment-responsive in-situ toxicity activation of a molecular drug (DSF) for augmented tumor chemotherapy., (© 2021. The Author(s).)

The fast development of nanomedicine and nanobiotechnology has enabled the emerging of versatile therapeutic modalities with high therapeutic efficiency and biosafety, among which nanosonosensitizer-involved sonodynamic therapy (SDT) employs ultrasound (US) as the exogenous activation source for inducing the production of reactive oxygen species (ROS) and disease therapy. The chemoreactive nanosonosensitizers are the critical components participating in the SDT process, which generally determine the SDT efficiency and therapeutic outcome. Compared to the traditional and mostly explored organic sonosensitizers, the recently developed inorganic chemoreactive nanosonosensitizers feature the distinct high stability, multifunctionality and significantly different SDT mechanism. This review dominantly discusses and highlights two types of inorganic nanosensitizers in sonodynamic treatments of various diseases and their underlying therapeutic mechanism, including US-activated generation of electrons (e - ) and holes (h + ) for facilitating the following ROS production and delivery of organic molecular sonosensitizers. Especially, this review proposes four strategies aiming for augmenting the SDT efficiency on antitumor and antibacterial applications based on inorganic sonosensitizers, including defect engineering, novel metal coupling, increasing electric conductivity and alleviating tumor hypoxia. The encountered challenges and critical issues facing these inorganic nanosonosensitzers are also highlighted and discussed for advancing their clinical translations., (© 2021 IOP Publishing Ltd.)

The application of nanotechnology in medicine aims at developing the precise theranostics of diseases by leveraging the extraordinary effects of engineered nanomedicines, materdicine, and biomaterials. However, finely controlling the biological behavior of nanomaterials in the complex living systems remains a great challenge in terms of accuracy and intelligence. Inspired by nature, biomimetics has become an attractive strategy based on the highly ordered natural biological structure for the development of clinically valuable materials and technologies, arising from the superior bioavailability. The rapid development of biomimetics in nanomedical applications prompts the authors to propose the concept of "nanobiomimetic medicine", which is a considerable subdiscipline in nanomedicine and materdicine that applies the concept and strategies of biomimetics to facilitate and promote the disease theranostics. Herein, the authors aim to furnish a state‐of‐the‐art review on the latest progress in the field of nanobiomimetic medicine. The design strategies, structural features and biological properties of biomimetic materials are initially introduced to reveal the inherent bionic mechanism and the potential structure‐function relationships. Furthermore, advances with respect to the applications of diverse biomimetic materials are comprehensively summarized. Finally, the current challenges and future direction of nanobiomimetic medicine are discussed and prospected in order to stimulate more biomimetic fundamental and technological breakthroughs in nanomedicine. [ABSTRACT FROM AUTHOR]

MXenes, a new class of two‐dimensional (2D) nanomaterials, have shown enormous potential for biological applications. Notably, the development of 2D MXenes in nanomedicine is still in its infancy. Herein, a distinct W1.33C i‐MXene with multiple theranostic functionalities, fast biodegradation, and satisfactory biocompatibility is explored. By designing a parent bulk laminate in‐plane ordered (W2/3Y1/3)2AlC ceramic and optionally etching aluminum (Al) and yttrium (Y) elements, 2D W1.33C i‐MXene nanosheets with ordered divacancies are efficiently fabricated. Especially, theoretical simulations reveal that W1.33C i‐MXene possesses a strong predominance of near‐infrared (NIR) absorbance. The constructed ultrathin W1.33C nanosheets feature excellent photothermal‐conversion effectiveness (32.5% at NIR I and 49.3% at NIR II) with desirable biocompatibility and fast degradation in normal tissue rather than in tumor tissue. Importantly, the multimodal‐imaging properties and photothermal‐ablation performance of W1.33C‐BSA nanosheets are systematically revealed and demonstrated both in vitro and in vivo. The underlying mechanism and regulation factors for the W1.33C‐BSA nanosheets‐induced hyperthermia ablation are also revealed by transcriptome and proteome sequencing. This work offers a paradigm that i‐MXenes achieve the tailoring biomedical applications through composition and structure design on the atomic scale. [ABSTRACT FROM AUTHOR]

Tumor hypoxia substantially lowers the treatment efficacy of oxygen‐relevant therapeutic modalities because the production of reactive oxygen species in oxygen‐relevant anticancer modalities is highly dependent on oxygen level in tumor tissues. Here a distinctive magnetothermodynamic anticancer strategy is developed that takes the advantage of oxygen‐irrelevant free radicals produced from magnetothermal decomposable initiators for inducing cancer‐cell apoptosis in vitro and tumor suppression in vivo. Free‐radical nanogenerator is constructed through in situ engineering of a mesoporous silica coating on the surface of superparamagnetic Mn and Co‐doped nanoparticles (MnFe2O4@CoFe2O4, denoted as Mag) toward multifunctionality, where mesoporous structure provides reservoirs for efficient loading of initiators and the Mag core serves as in situ heat source under alternating magnetic field (AMF) actuation. Upon exposure to an exogenous AMF, the magnetic hyperthermia effect of superparamagnetic core lead to the rapid decomposition of the loaded/delivered initiators (AIPH) to produce oxygen‐irrelevant free radicals. Both the magnetothermal effect and generation of toxic free radicals under AMF actuation are synergistically effective in promoting cancer‐cell death and tumor suppression in the hypoxic tumor microenvironment. The prominent therapeutic efficacy of this radical nanogenerator represents an intriguing paradigm of oxygen‐irrelevant nanoplatform for AMF‐initiated synergistic cancer treatment. [ABSTRACT FROM AUTHOR]

As an essential trace element in the human body, transitional metal copper (Cu) ions are the bioactive components within the body featuring dedicated biological effects such as promoting angiogenesis and influencing lipid/glucose metabolism. The recent substantial advances of nanotechnology and nanomedicine promote the emerging of distinctive Cu‐involved biomaterial nanoplatforms with intriguing theranostic performances in biomedicine, which are originated from the biological effects of Cu species and the physiochemical attributes of Cu‐composed nanoparticles. Based on the very‐recent significant progresses of Cu‐involved nanotheranostics, this work highlights and discusses the principles, progresses, and prospects on the elaborate design and rational construction of Cu‐composed functional nanoplatforms for a diverse array of biomedical applications, including photonic nanomedicine, catalytic nanotherapeutics, antibacteria, accelerated tissue regeneration, and bioimaging. The engineering of Cu‐based nanocomposites for synergistic nanotherapeutics is also exemplified, followed by revealing their intrinsic biological effects and biosafety for revolutionizing their clinical translation. Finally, the underlying critical concerns, unresolved hurdles, and future prospects on their clinical uses are analyzed and an outlook is provided. By entering the "Copper Age," these Cu‐involved nanotherapeutic modalities are expected to find more broad biomedical applications in preclinical and clinical phases, despite the current research and developments still being in infancy. [ABSTRACT FROM AUTHOR]

[Display omitted] Iron accumulation and lipid peroxidation form the basis of ferroptosis, potentially circumventing the limitations of apoptosis in cancer treatment. Owing to the lack of potent ferroptosis inducers, the development of efficient ferroptosis-based therapeutic agents and protocols against cancers is highly challenging. Inspired by the topological effect of nanoparticles in modulating cellular function/status, a specific tetrapod ferroptosis-inducer iron-palladium (FePd) nanocrystal was rationally engineered for physically activated autophagy-augmented ferroptosis and enhanced cancer immunotherapy. Specifically, the tetrapod FePd nanocrystal featured strong peroxidase-/glutathione oxidase-mimicking bioactivities, which promoted cancer cell ferroptosis. The special spiky morphology and nanostructure of the FePd nanocrystal simultaneously induced autophagy, which augmented ferroptosis in cancer cells and triggered the release of inflammatory cytokines in macrophages for strengthening anti-PD-L1-antibody mediated immunotherapy, synergistically achieving the maximal antineoplastic effect in three tumor-bearing animal models. This unique physical activation strategy for efficient cancer treatment via precise morphological tuning represents a paradigm for nanomedicine design for efficient tumor treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] • A nanoreactor was designed for SDT-promoted calcium overload and pyroptotic antitumor treatment. • Achieving synergistic tumor-therapeutic efficacy and outcome by the engineered nanomedicine. • Mechanistic clarification of SDT-promoted calcium overload for pyroptosis induction. Pyroptosis, an inflammatory regulated cell death (RCD), can be effectively driven by calcium overload in Gasdermin E (GSDME)-expressed tumor cells, which provides a distinct and effective pathway to activate a strong inflammatory response in treating refractory carcinomas. Inspired by the fact that the mitochondrial Ca2+-buffering capacity can be influenced and even destroyed by reactive oxygen species (ROS), we herein have designed and engineered a nanosonosensitizer (PpIX)-based liposomal nanosystem, which simultaneously co-encapsulated calcium-supplement CaO 2 and DNA methyltransferase (DNMT) inhibitor Decitabine (DAC) for inducing pyroptosis in the context of mitochondria dysfunction. Mechanistically, calcium overload can be logically achieved by the synergism of mitochondrial dysfunction with exogenous Ca2+ delivery, which promotes the release of cytochrome c (cyt c), activates CAS-3 cleavage to GSDME into cytotoxic GSDME-N terminals, and then triggers cancer cell pyroptosis. Taken together, a markedly enhanced antitumor efficiency is achieved via synergistic sonodynamic therapy (SDT) and calcium overload for inducing GSDME-dependent pyroptotic tumor therapy, which is expected to provide a distinct cancer-therapeutic modality based on pyroptosis of cancer cells for malignant carcinomas. [ABSTRACT FROM AUTHOR]

Catalytic cascade transformations, which occur in spatially constrained tumor environment to generate therapeutic moieties from prodrugs or intrinsic species, are highly desirable for precise cancer therapy. Nevertheless, it is high challenging to engineer a cascade nanoreactor with tumor microenvironment (TME)-responsive capability for synergistic tumor therapy. Inspired by the biocatalytic cascades in biological processes, here, a tumor-specific nanoreactor was established to activate cascade reactions for oxidative stress-augmented chemotherapy by the integration of an artificial enzyme, Pt(IV)-based prodrug (Pt(IV)), with Cu(II)-based metal-organic frameworks (CuMOF). Upon internalization of CuMOF@Pt(IV) by tumor cells, in addition to chemotherapeutic effect, the activated cisplatin by glutathione (GSH) reduction is capable of acting as an artificial enzyme to elevate the hydrogen peroxide (H 2 O 2) level through cascade reactions for augmenting the therapeutic efficacy of Cu+-mediated chemodynamic therapy (CDT). Meanwhile, CuMOF@Pt(IV) specifically deplete overexpressed GSH at tumor sites, thus amplifying tumor oxidative stress, and finally leading to augmented antitumor efficacy. The orchestrated cooperative effect of chemotherapy and oxidative stress presents splendid therapeutic efficacy on tumor-bearing mice with negligible adverse effects. Therefore, this cascade nanoreactor provides exciting opportunities to develop complementary therapeutic modalities for precise cancer treatment. [Display omitted] [ABSTRACT FROM AUTHOR]