Oral Nanomedicine: Challenges and Opportunities.

Compared to injection administration, oral administration is free of discomfort, wound infection, and complications and has a higher compliance rate for patients with diverse diseases. However, oral administration reduces the bioavailability of medicines, especially biologics (e.g., peptides, proteins, and antibodies), due to harsh gastrointestinal biological barriers. In this context, the development and prosperity of nanotechnology have helped improve the bioactivity and oral availability of oral medicines. On this basis, first, the biological barriers to oral administration are discussed, and then oral nanomedicine based on organic and inorganic nanomaterials and their biomedical applications in diverse diseases are reviewed. Finally, the challenges and potential opportunities in the future development of oral nanomedicine, which may provide a vital reference for the eventual clinical transformation and standardized production of oral nanomedicine, are put forward.

Transcriptome analysis unveils the mechanisms of lipid metabolism response to grayanotoxin I stress in Spodoptera litura.

Background: Spodoptera litura (tobacco caterpillar, S. litura) is a pest of great economic importance due to being a polyphagous and world-distributed agricultural pest. However, agricultural practices involving chemical pesticides have caused resistance, resurgence, and residue problems, highlighting the need for new, environmentally friendly methods to control the spread of S. litura. Aim: This study aimed to investigate the gut poisoning of grayanotoxin I, an active compound found in Pieris japonica, on S. litura, and to explore the underlying mechanisms of these effects. Methods: S. litura was cultivated in a laboratory setting, and their survival rate, growth and development, and pupation time were recorded after grayanotoxin I treatment. RNA-Seq was utilized to screen for differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to determine the functions of these DEGs. ELISA was employed to analyze the levels of lipase, 3-hydroxyacyl-CoA dehydrogenase (HOAD), and acetyl-CoA carboxylase (ACC). Hematoxylin and Eosin (H & E) staining was used to detect the development of the fat body. Results: Grayanotoxin I treatment significantly suppressed the survival rate, growth and development, and pupation of S. litura. RNA-Seq analysis revealed 285 DEGs after grayanotoxin I exposure, with over 16 genes related to lipid metabolism. These 285 DEGs were enriched in the categories of cuticle development, larvae longevity, fat digestion and absorption. Grayanotoxin I treatment also inhibited the levels of FFA, lipase, and HOAD in the hemolymph of S. litura. Conclusion: The results of this study demonstrated that grayanotoxin I inhibited the growth and development of S. litura. The mechanisms might, at least partly, be related to the interference of lipid synthesis, lipolysis, and fat body development. These findings provide valuable insights into a new, environmentally-friendly plant-derived insecticide, grayanotoxin I, to control the spread of S. litura.

Selective CO2 Reduction to Ethylene Mediated by Adaptive Small-molecule Engineering of Copper-based Electrocatalysts.

Electrochemical CO2 reduction reaction (CO2 RR) over Cu catalysts exhibits enormous potential for efficiently converting CO2 to ethylene (C2 H4 ). However, achieving high C2 H4 selectivity remains a considerable challenge due to the propensity of Cu catalysts to undergo structural reconstruction during CO2 RR. Herein, we report an in situ molecule modification strategy that involves tannic acid (TA) molecules adaptive regulating the reconstruction of a Cu-based material to a pathway that facilitates CO2 reduction to C2 H4 products. An excellent Faraday efficiency (FE) of 63.6 % on C2 H4 with a current density of 497.2 mA cm-2 in flow cell was achieved, about 6.5 times higher than the pristine Cu catalyst which mainly produce CH4 . The in situ X-ray absorption spectroscopy and Raman studies reveal that the hydroxyl group in TA stabilizes Cuδ+ during the CO2 RR. Furthermore, theoretical calculations demonstrate that the Cuδ+ /Cu0 interfaces lower the activation energy barrier for *CO dimerization, and hydroxyl species stabilize the *COH intermediate via hydrogen bonding, thereby promoting C2 H4 production. Such molecule engineering modulated electronic structure provides a promising strategy to achieve highly selective CO2 reduction to value-added chemicals.

Harnessing inhaled nanoparticles to overcome the pulmonary barrier for respiratory disease therapy.

The lack of effective treatments for pulmonary diseases presents a significant global health burden, primarily due to the challenges posed by the pulmonary barrier that hinders drug delivery to the lungs. Inhaled nanomedicines, with their capacity for localized and precise drug delivery to specific pulmonary pathologies through the respiratory route, hold tremendous promise as a solution to these challenges. Nevertheless, the realization of efficient and safe pulmonary drug delivery remains fraught with multifaceted challenges. This review summarizes the delivery barriers associated with major pulmonary diseases, the physicochemical properties and drug formulations affecting these barriers, and emphasizes the design advantages and functional integration of nanomedicine in overcoming pulmonary barriers for efficient and safe local drug delivery. The review also deliberates on established nanocarriers and explores drug formulation strategies rooted in these nanocarriers, thereby furnishing essential guidance for the rational design and implementation of pulmonary nanotherapeutics. Finally, this review cast a forward-looking perspective, contemplating the clinical prospects and challenges inherent in the application of inhaled nanomedicines for respiratory diseases.

Effects of Litsea cubeba essential oil on growth performance, blood antioxidation, immune function, apparent digestibility of nutrients, and fecal microflora of pigs.

The purpose of this experiment was to investigate the effects of Litsea cubeba essential oil (LCO) on the growth performance, blood antioxidation, immune function, apparent digestibility of nutrients, and fecal microflora in fattening pigs. A total of 120 pigs were randomly assigned to five groups, with six replicate pens per treatment and four pigs per pen, and they were fed basal diet, chlortetracycline (CTC), and low-, medium-, and high-concentration LCO. The results of the study showed that compared with the control treatment and CTC addition treatment of the basic diet, the catalase level in the serum of the pigs treated with 500 mg/kg LCO in the diet of finishing pigs was significantly increased (p < 0.05). The apparent digestibility of crude protein, crude ash, and calcium in pigs with different levels of LCO was significantly increased compared with the control treatments fed the basal diet (p < 0.05). In addition, compared with the control treatment fed the basal diet and the treatment with CTC, the apparent digestibility of ether extract in pigs treated with medium-dose LCO was significantly increased (p < 0.05), and the apparent digestibility of pigs was significantly increased after the addition of low-dose LCO (p < 0.05). Among the genera, the percentage abundance of SMB53 (p < 0.05) was decreased in the feces of the CTC group when compared to that in the medium-LCO group. At the same time, the relative abundance of L7A_E11 was markedly decreased in the feces of the control and medium- and high-concentration LCO group than that in the CTC group (p < 0.05). In conclusion, adding the level of 250 mg/kg LCO in the diet of pig could improve the growth performance and blood physiological and biochemical indicators of pigs, improve the antioxidant level of body and the efficiency of digestion and absorption of nutrients, and show the potential to replace CTC.

Oral Hydrogel Microbeads-Mediated In Situ Synthesis of Selenoproteins for Regulating Intestinal Immunity and Microbiota.

Selenoprotein plays a crucial role in immune cells and inflammatory regulation. However, as a protein drug that is easily denatured or degraded in the acidic environment of the stomach, efficient oral delivery of selenoprotein is a great challenge. Herein, we innovated an oral hydrogel microbeads-based biochemical strategy that can in situ synthesize selenoproteins, therefore bypassing the necessity and harsh conditions for oral protein delivery while effectively generating selenoproteins for therapeutic applications. The hydrogel microbeads were synthesized by coating hyaluronic acid-modified selenium nanoparticles with a protective shell of calcium alginate (SA) hydrogel. We tested this strategy in mice with inflammatory bowel disease (IBD), one of the most representative diseases related to intestinal immunity and microbiota. Our results revealed that hydrogel microbeads-mediated in situ synthesis of selenoproteins could prominently reduce proinflammatory cytokines secretion and mediate immune cells (e.g., reduce neutrophils and monocytes and increase immune regulatory T cells) to effectively relieve colitis-associated symptoms. This strategy was also able to regulate gut microbiota composition (increase probiotics abundance and suppress detrimental communities) to maintain intestinal homeostasis. Considering intestinal immunity and microbiota widely associated with cancers, infections, inflammations, etc., this in situ selenoprotein synthesis strategy might also be possibly applied to broadly tackle various diseases.

Bioinspired Mild Photothermal Effect-Reinforced Multifunctional Fiber Scaffolds Promote Bone Regeneration.

Bone fractures are often companied with poor bone healing and high rates of infection. Early recruitment of mesenchymal stem cells (MSCs) is critical for initiating efficient bone repair, and mild thermal stimulation can accelerate the recovery of chronic diseases. Here, a bioinspired, staged photothermal effect-reinforced multifunctional scaffold was fabricated for bone repair. Uniaxially aligned electrospun polycaprolactone nanofibers were doped with black phosphorus nanosheets (BP NSs) to endow the scaffold with excellent near-infrared (NIR) responsive capability. Apt19S was then decorated on the surface of the scaffold to selectively recruit MSCs toward the injured site. Afterward, microparticles of phase change materials loaded with antibacterial drugs were also deposited on the surface of the scaffold, which could undergo a solid-to-liquid phase transition above 39 °C, triggering the release of payload to eliminate bacteria and prevent infection. Under NIR irradiation, photothermal-mediated up-regulation of heat shock proteins and accelerated biodegradation of BP NSs could promote the osteogenic differentiation of MSCs and biomineralization. Overall, this strategy shows the ability of bacteria elimination, MSCs recruitment, and bone regeneration promotion with the assistance of photothermal effect in vitro and in vivo, which emphasizes the design of a bioinspired scaffold and its potential for a mild photothermal effect in bone tissue engineering.

Nanomedicine for T-Cell Mediated Immunotherapy.

T-cell immunotherapy offers outstanding advantages in the treatment of various diseases, and with the selection of appropriate targets, efficient disease treatment can be achieved. T-cell immunotherapy has made great progress, but clinical results show that only a small proportion of patients can benefit from T-cell immunotherapy. The extensive mechanistic work outlines a blueprint for using T cells as a new option for immunotherapy, but also presents new challenges, including the balance between different fractions of T cells, the inherent T-cell suppression patterns in the disease microenvironment, the acquired loss of targets, and the decline of T-cell viability. The diversity, flexibility, and intelligence of nanomedicines give them great potential for enhancing T-cell immunotherapy. Here, how T-cell immunotherapy strategies can be adapted with different nanomaterials to enhance therapeutic efficacy is discussed. For two different pathological states, immunosuppression and immune activation, recent advances in nanomedicines for T-cell immunotherapy in diseases such as cancers, rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, and diabetes are summarized. With a focus on T-cell immunotherapy, this review highlights the outstanding advantages of nanomedicines in disease treatment, and helps advance one's understanding of the use of nanotechnology to enhance T-cell immunotherapy.

Carbon nanomaterials for drug delivery and tissue engineering.

Carbon nanomaterials are some of the state-of-the-art materials used in drug-delivery and tissue-engineering research. Compared with traditional materials, carbon nanomaterials have the advantages of large specific surface areas and unique properties and are more suitable for use in drug delivery and tissue engineering after modification. Their characteristics, such as high drug loading and tissue loading, good biocompatibility, good targeting and long duration of action, indicate their great development potential for biomedical applications. In this paper, the synthesis and application of carbon dots (CDs), carbon nanotubes (CNTs) and graphene in drug delivery and tissue engineering are reviewed in detail. In this review, we discuss the current research focus and existing problems of carbon nanomaterials in order to provide a reference for the safe and effective application of carbon nanomaterials in drug delivery and tissue engineering.

Minimally invasive nanomedicine: nanotechnology in photo-/ultrasound-/radiation-/magnetism-mediated therapy and imaging.

Traditional treatments such as chemotherapy and surgery usually cause severe side effects and excruciating pain. The emergence of nanomedicines and minimally invasive therapies (MITs) has brought hope to patients with malignant diseases. Especially, minimally invasive nanomedicines (MINs), which combine the advantages of nanomedicines and MITs, can effectively target pathological cells/tissues/organs to improve the bioavailability of drugs, minimize side effects and achieve painless treatment with a small incision or no incision, thereby acquiring good therapeutic effects. In this review, we provide a comprehensive review of the research status and challenges of MINs, which generally refers to the medical applications of nanotechnology in photo-/ultrasound-/radiation-/magnetism-mediated therapy and imaging. Additionally, we also discuss their combined application in various fields including cancers, cardiovascular diseases, tissue engineering, neuro-functional diseases, and infectious diseases. The prospects, and potential bench-to-bedside translation of MINs are also presented in this review. We expect that this review can inspire the broad interest for a wide range of readers working in the fields of interdisciplinary subjects including (but not limited to) chemistry, nanomedicine, bioengineering, nanotechnology, materials science, pharmacology, and biomedicine.

2D materials-based nanomedicine: From discovery to applications.

Due to their unique physicochemical characteristics, 2D materials have attracted more and more attention in the biomedicine field. Currently, 2D materials-based nanomedicines have been extensively applied in various diseases including cancer, bacterial infection, tissue engineering, biological protection, neurodegenerative diseases, and cardiovascular disease. Depending on their various characteristics, these 2D nanomedicines exert their therapeutic effect in different ways, showing great clinical application prospects. Herein, we focus on the various biomedical applications of 2D materials-based nanomedicine. The structures and characteristics of several typical 2D nanomaterials with different configurations and their corresponding biomedical applications are first introduced. Then, the potential of 2D nanomedicines on therapeutic and imaging and their biological functionalization are discussed. Furthermore, the therapeutic potentials of 2D nanomedicines in various diseases are also comprehensively summarized. At last, the challenges and perspectives for the advancement of 2D nanomedicines in clinical transformation are outlooks.

A facile and general method for synthesis of antibiotic-free protein-based hydrogel: Wound dressing for the eradication of drug-resistant bacteria and biofilms.

Antibacterial protein hydrogels are receiving increasing attention in the aspect of bacteria-infected-wound healing. However, bacterial drug resistance and biofilm infections lead to hard healing of wounds, thus the construction of biological agents that can overcome these issues is essential. Here, a simple and universal method to construct antibiotic-free protein hydrogel with excellent biocompatibility and superior antibacterial activity against drug-resistant bacteria and biofilms was developed. The green industrial microbicide tetrakis (hydroxymethyl) phosphonium sulfate (THPS) as cross-linking agent can be quickly cross-linked with model protein bovine serum albumin (BSA) to form antibacterial hydrogel through simple mixing without any other initiators, subsequently promoting drug-resistance bacteria-infected wound healing. This simple gelatinization strategy allows at least ten different proteins to form hydrogels (e.g. BSA, human serum albumin (HSA), egg albumin, chymotrypsin, trypsin, lysozyme, transferrin, myohemoglobin, hemoglobin, and phycocyanin) under the same conditions, showing prominent universality. Furthermore, drug-resistance bacteria and biofilm could be efficiently destroyed by the representative BSA hydrogel (B-Hydrogel) with antibacterial activity, overcoming biofilm-induced bacterial resistance. The in vivo study demonstrated that the B-Hydrogel as wound dressing can promote reepithelization to accelerate the healing of methicillin-resistant staphylococcus aureus (MRSA)-infected skin wounds without inducing significant side-effect. This readily accessible antibiotic-free protein-based hydrogel not only opens an avenue to provide a facile, feasible and general gelation strategy, but also exhibits promising application in hospital and community MRSA disinfection and treatment.

Microalgae-based oral microcarriers for gut microbiota homeostasis and intestinal protection in cancer radiotherapy.

Protecting the whole small intestine from radiation-induced intestinal injury during the radiotherapy of abdominal or pelvic solid tumors remains an unmet clinical need. Amifostine is a promising selective radioprotector for normal tissues. However, its oral application in intestinal radioprotection remains challenging. Herein, we use microalga Spirulina platensis as a microcarrier of Amifostine to construct an oral delivery system. The system shows comprehensive drug accumulation and effective radioprotection in the whole small intestine that is significantly superior to free drug and its enteric capsule, preventing the radiation-induced intestine injury and prolonging the survival without influencing the tumor regression. It also shows benefits on the gut microbiota homeostasis and long-term safety. Based on a readily available natural microcarrier, this work presents a convenient oral delivery system to achieve effective radioprotection for the whole small intestine, providing a competitive strategy with great clinical translation potential.

Emerging vaccine nanotechnology: From defense against infection to sniping cancer.

Looking retrospectively at the development of humanity, vaccination is an unprecedented medical landmark that saves lives by harnessing the human immune system. During the ongoing coronavirus disease 2019 (COVID-19) pandemic, vaccination is still the most effective defense modality. The successful clinical application of the lipid nanoparticle-based Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines highlights promising future of nanotechnology in vaccine development. Compared with conventional vaccines, nanovaccines are supposed to have advantages in lymph node accumulation, antigen assembly, and antigen presentation; they also have, unique pathogen biomimicry properties because of well-organized combination of multiple immune factors. Beyond infectious diseases, vaccine nanotechnology also exhibits considerable potential for cancer treatment. The ultimate goal of cancer vaccines is to fully mobilize the potency of the immune system as a living therapeutic to recognize tumor antigens and eliminate tumor cells, and nanotechnologies have the requisite properties to realize this goal. In this review, we summarize the recent advances in vaccine nanotechnology from infectious disease prevention to cancer immunotherapy and highlight the different types of materials, mechanisms, administration methods, as well as future perspectives.

A Cascade Nanozyme with Amplified Sonodynamic Therapeutic Effects through Comodulation of Hypoxia and Immunosuppression against Cancer.

The tumor microenvironment (TME) featured by immunosuppression and hypoxia is pivotal to cancer deterioration and metastasis. Thus, regulating the TME to improve cancer cell ablation efficiency has received extensive interest in oncotherapy. However, to reverse the immunosuppression and alleviate hypoxia simultaneously in the TME are major challenges for effective cancer therapy. Herein, a multifunctional platform based on Au nanoparticles and a carbon dots modified hollow black TiO2 nanosphere (HABT-C) with intrinsic cascade enzyme mimetic activities is prepared for reversing immunosuppression and alleviating hypoxia in the TME. The HABT-C NPs possess triple-enzyme mimetic activity to act as self-cascade nanozymes, which produce sufficient oxygen to alleviate hypoxia and generate abundant ROS. The theoretical analysis demonstrates that black TiO2 facilitates absorption of H2O and O2, separation of electron-holes, and generation of ROS, consequently amplifying the sonodynamic therapy (SDT) efficiency. Specifically, HABT-C exhibits favorable inhibition of immunosuppressive mediator expression, along with infiltrating of immune effector cells into the TME and reversing the immunosuppression in the TME. As a result, HABT-C can effectively kill tumor cells via eliciting immune infiltration, alleviating hypoxia, and improving SDT efficiency. This cascade nanozyme-based platform (HABT-C@HA) will provide a strategy for highly efficient SDT against cancer by modulation of hypoxia and immunosuppression in the TME.

Nano-bio interfaces effect of two-dimensional nanomaterials and their applications in cancer immunotherapy.

The field of two-dimensional (2D) nanomaterial-based cancer immunotherapy combines research from multiple subdisciplines of material science, nano-chemistry, in particular nano-biological interactions, immunology, and medicinal chemistry. Most importantly, the "biological identity" of nanomaterials governed by bio-molecular corona in terms of bimolecular types, relative abundance, and conformation at the nanomaterial surface is now believed to influence blood circulation time, bio-distribution, immune response, cellular uptake, and intracellular trafficking. A better understanding of nano-bio interactions can improve utilization of 2D nano-architectures for cancer immunotherapy and immunotheranostics, allowing them to be adapted or modified to treat other immune dysregulation syndromes including autoimmune diseases or inflammation, infection, tissue regeneration, and transplantation. The manuscript reviews the biological interactions and immunotherapeutic applications of 2D nanomaterials, including understanding their interactions with biological molecules of the immune system, summarizes and prospects the applications of 2D nanomaterials in cancer immunotherapy.

NIR-II Responsive Hydrogel as an Angiogenesis Inhibition Agent for Tumor Microenvironment Reprogramming.

Regulation of angiogenesis is a great challenge for effective anticancer therapy. Generally, anti-angiogenic therapies are focused on inhibition of inducers involved in pro-angiogenic communication pathways. Despite the great potential of anti-angiogenic therapy, engineering efficient angiogenesis inhibition agents (AIAs) is still a formidable challenge, since most anti-angiogenic therapies are limited due to the cancer recurrence via compensatory expression of different angiogenic mediators. Herein, we present a new strategy of near-infrared-II (NIR-II) responsive hydrogel AIAs, constructed by incorporation of nitric oxide (NO) precursor (BNN6) and 2D WO2.9 nanosheets within hydrogel (WB@hydrogel). Because of the defect/2D engineering, the bandgap of the WO2.9 nanosheets narrows, which extends the absorption to the NIR-II region. It offers a favorable NIR-II controlled manner for NO generation through irradiation time and light intensity. The continuous supply of NO can activate the expression of wild-type p53 protein and further reverse the transcriptional expression of pro- and anti-angiogenic factors of the tumor microenvironment (TME), subsequently alternating pro-angiogenic TME to anti-angiogenic TME. In the murine tumor model, this method achieved high tumor growth inhibition (TGI) rate and excellent anti-recurrence efficiency.

Cryogenic Exfoliation of 2D Stanene Nanosheets for Cancer Theranostics.

Stanene (Sn)-based materials have been extensively applied in industrial production and daily life, but their potential biomedical application remains largely unexplored, which is due to the absence of the appropriate and effective methods for fabricating Sn-based biomaterials. Herein, we explored a new approach combining cryogenic exfoliation and liquid-phase exfoliation to successfully manufacture two-dimensional (2D) Sn nanosheets (SnNSs). The obtained SnNSs exhibited a typical sheet-like structure with an average size of ~ 100 nm and a thickness of ~ 5.1 nm. After PEGylation, the resulting PEGylated SnNSs (SnNSs@PEG) exhibited good stability, superior biocompatibility, and excellent photothermal performance, which could serve as robust photothermal agents for multi-modal imaging (fluorescence/photoacoustic/photothermal imaging)-guided photothermal elimination of cancer. Furthermore, we also used first-principles density functional theory calculations to investigate the photothermal mechanism of SnNSs, revealing that the free electrons in upper and lower layers of SnNSs contribute to the conversion of the photo to thermal. This work not only introduces a new approach to fabricate 2D SnNSs but also establishes the SnNSs-based nanomedicines for photonic cancer theranostics. This new type of SnNSs with great potential in the field of nanomedicines may spur a wave of developing Sn-based biological materials to benefit biomedical applications.

Ca2+-supplying black phosphorus-based scaffolds fabricated with microfluidic technology for osteogenesis.

Effective osteogenesis remains a challenge in the treatment of bone defects. The emergence of artificial bone scaffolds provides an attractive solution. In this work, a new biomineralization strategy is proposed to facilitate osteogenesis through sustaining supply of nutrients including phosphorus (P), calcium (Ca), and silicon (Si). We developed black phosphorus (BP)-based, three-dimensional nanocomposite fibrous scaffolds via microfluidic technology to provide a wealth of essential ions for bone defect treatment. The fibrous scaffolds were fabricated from 3D poly (l-lactic acid) (PLLA) nanofibers (3D NFs), BP nanosheets, and hydroxyapatite (HA)-porous SiO2 nanoparticles. The 3D BP@HA NFs possess three advantages: i) stably connected pores allow the easy entrance of bone marrow-derived mesenchymal stem cells (BMSCs) into the interior of the 3D fibrous scaffolds for bone repair and osteogenesis; ii) plentiful nutrients in the NFs strongly improve osteogenic differentiation in the bone repair area; iii) the photothermal effect of fibrous scaffolds promotes the release of elements necessary for bone formation, thus achieving accelerated osteogenesis. Both in vitro and in vivo results demonstrated that the 3D BP@HA NFs, with the assistance of NIR laser, exhibited good performance in promoting bone regeneration. Furthermore, microfluidic technology makes it possible to obtain high-quality 3D BP@HA NFs with low costs, rapid processing, high throughput and mass production, greatly improving the prospects for clinical application. This is also the first BP-based bone scaffold platform that can self-supply Ca2+, which may be the blessedness for older patients with bone defects or patients with damaged bones as a result of calcium loss.

Stanene-Based Nanosheets for ß-Elemene Delivery and Ultrasound-Mediated Combination Cancer Therapy.

Ultrasound (US)-mediated sonodynamic therapy (SDT) has emerged as a superior modality for cancer treatment owing to the non-invasiveness and high tissue-penetrating depth. However, developing biocompatible nanomaterial-based sonosensitizers with efficient SDT capability remains challenging. Here, we employed a liquid-phase exfoliation strategy to obtain a new type of two-dimensional (2D) stanene-based nanosheets (SnNSs) with a band gap of 2.3 eV, which is narrower than those of the most extensively studied nano-sonosensitizers, allowing a more efficient US-triggered separation of electron (e- )-hole (h+ ) pairs for reactive oxygen species (ROS) generation. In addition, we discovered that such SnNSs could also serve as robust near-infrared (NIR)-mediated photothermal therapy (PTT) agents owing to their efficient photothermal conversion, and serve as nanocarriers for anticancer drug delivery owing to the inherent 2D layered structure. This study not only presents general nanoplatforms for SDT-enhanced combination cancer therapy, but also highlights the utility of 2D SnNSs to the field of nanomedicine.