Ca-doping interfacial engineering and glycolysis enable rapid charge separation for efficient phototherapy of MRSA-infected wounds.

Methicillin-resistant Staphylococcus aureus (MRSA) is the primary pathogenic agent responsible for epidermal wound infection and suppuration, seriously threatening the life and health of human beings. To address this fundamental challenge, we propose a heterojunction nanocomposite (Ca-CN/MnS) comprised of Ca-doped g-C3N4 and MnS for the therapy of MRSA-accompanied wounds. The Ca doping leads to a reduction in both the bandgap and the singlet state S1-triplet state T2 energy gap (ΔEST). The Ca doping also facilitates the two-photon excitation, thus remarkably promoting the separation and transfer of 808 nm near-infrared (NIR) light-triggered electron-hole pairs together with the built-in electric field. Thereby, the production of reactive oxygen species and heat are substantially augmented nearby the nanocomposite under 808 nm NIR light irradiation. Consequently, an impressive photocatalytic MRSA bactericidal efficiency of 99.98 ± 0.02 % is achieved following exposure to NIR light for 20 min. The introduction of biologically functional elements (Ca and Mn) can up-regulate proteins such as pyruvate kinase (PKM), L-lactate dehydrogenase (LDHA), and calcium/calmodulin-dependent protein kinase (CAMKII), trigger the glycolysis and calcium signaling pathway, promote cell proliferation, cellular metabolism, and angiogenesis, thereby expediting the wound-healing process. This heterojunction nanocomposite, with its precise charge-transfer pathway, represents a highly effective bactericidal and bioactive system for treating multidrug-resistant bacterial infections and accelerating tissue repair. STATEMENT OF SIGNIFICANCE: Due to the bacterial resistance, developing an antibiotic-free and highly effective bactericidal strategy to treat bacteria-infected wounds is critical. We have designed a heterojunction consisting of calcium doped g-C3N4 and MnS (Ca-CN/MnS) that can rapidly kill methicillin-resistant Staphylococcus aureus (MRSA) without damaging normal tissue through a synergistic effect of two-photon stimulated photothermal and photodynamic therapy. In addition, the release of trace amounts of biofunctional elements Mn and Ca triggers glycolysis and calcium signaling pathways that promote cellular metabolism and cell proliferation, contributing to tissue repair and wound healing.

Dual elemental doping activated signaling pathway of angiogenesis and defective heterojunction engineering for effective therapy of MRSA-infected wounds.

Multi-drug resistant bacterial infections pose a significant threat to human health. Thus, the development of effective bactericidal strategies is a pressing concern. In this study, a ternary heterostructure (Zn-CN/P-GO/BiS) comprised of Zn-doped graphite phase carbon nitride (g-C3N4), phosphorous-doped graphene oxide (GO) and bismuth sulphide (Bi2S3) is constructed for efficiently treating methicillin-resistant Staphylococcus aureus (MRSA)-infected wound. Zn doping-induced defect sites in g-C3N4 results in a reduced band gap (ΔE) and a smaller energy gap (ΔEST) between the singlet state S1 and triplet state T1, which favours two-photon excitation and accelerates electron transfer. Furthermore, the formation of an internal electric field at the ternary heterogeneous interface optimizes the charge transfer pathway, inhibits the recombination of electron-hole pairs, improves the photodynamic effect of g-C3N4, and enhances its catalytic performance. Therefore, the Zn-CN/P-GO/BiS significantly augments the production of reactive oxygen species and heat under 808 nm NIR (0.67 W cm-2) irradiation, leading to the elimination of 99.60% ± 0.07% MRSA within 20 min. Additionally, the release of essential trace elements (Zn and P) promotes wound healing by activating hypoxia-inducible factor-1 (HIF-1) and peroxisome proliferator-activated receptors (PPAR) signaling pathways. This work provides unique insight into the rapid antibacterial applications of trace element doping and two-photon excitation.

BiTiS3 bio-transducer with explosive on-demand generation of NO gas for synergetic cancer therapy.

Combined photothermal therapy and nitric oxide (NO)-mediated gas therapy has shown great potential as a cancer treatment. However, the on-demand release of NO at a high concentration presents a challenge owing to the lack of an ideal bio-transducer with a high loading capacity of NO donors and sufficient energy to induce NO release. Here, we present a new 2D BiTiS3 nanosheet that is synthesized, loaded with the NO donor (BNN6), and conjugated with PEG-iRGD to produce a multifunctional bio-transducer (BNN6-BiTiS3-iRGD) for the on-demand production of NO. The BiTiS3 nanosheets not only have a high loading capacity of NO donors (750%), but also exhibit a high photothermal conversion efficiency (59.5%) after irradiation by a 1064-nm laser at 0.5 W/cm2. As a result of the above advantages, the temporal-controllable generation of NO within a large dynamic range (from 0 to 344 µM) is achieved by adjusting power densities, which is among the highest efficiency values reported for NO generators so far. Moreover, the targeted accumulation of BNN6-BiTiS3-iRGD at tumor sites leads to spatial-controllable NO release. In vitro and in vivo assessments demonstrate synergistic NO gas therapy with mild photothermal therapy based on BNN6-BiTiS3-iRGD. Our work provides insights into the design and application of other 2D nanomaterial-based therapeutic platforms.

Synthesis of germanium/germanium phosphide in-plane heterostructure with efficient photothermal and enhanced photodynamic effects in the second near-infrared biowindow.

Inspired by the bifunctional phototherapy agents (PTAs), constructing compact PTAs with efficient photothermal therapy (PTT) and photodynamic therapy (PDT) effects in the near-infrared (NIR-II) biowindow is crucial for high therapeutic efficacy. Herein, none-layered germanium (Ge) is transformed to layered Ge/germanium phosphide (Ge/GeP) structure, and a novel two-dimensional sheet-like compact S-scheme Ge/GeP in-plane heterostructure with a large extinction coefficient of 15.66 L/g cm-1 at 1,064 nm is designed and demonstrated. In addition to the outstanding photothermal effects, biocompatibility and degradability, type I and type II PDT effects are activated by a single laser. Furthermore, enhanced reactive oxygen species generation under longer wavelength NIR laser irradiation is achieved, and production of singlet oxygen and superoxide radical upon 1,064 nm laser irradiation is more than double that under 660 nm laser irradiation. The S-scheme charge transfer mechanism between Ge and GeP, is demonstrated by photo-irradiated Kelvin probe force microscopy and electron spin resonance analysis. Thus, the obtained S-scheme Ge/GeP in-plane heterostructure shows synergistic therapeutic effects of PTT/PDT both in vitro and in vivo in the NIR-II biowindow and the novel nanoplatform with excellent properties has large clinical potential.

Anti-tumor immunity and ferroptosis of hepatocellular carcinoma are enhanced by combined therapy of sorafenib and delivering modified GO-based PD-L1 siRNAs.

Programmed cell death receptor ligand 1 (PD-L1)/PD-1 signaling has been exploited to design inhibitors that deliver promising clinical outcome albeit with limited efficacy. Herein, we prepare graphene oxide (GO)-PEI-PEG with low cytotoxicity and long stability and GO-PEI-PEG delivers PD-L1 siRNAs to hepatocellular carcinoma (HCC) cells by the endocytosis-lysosome pathway. The functional GO-PEI-PEG/PD-L1 siRNAs decrease PD-L1 and PD-1 abundance, increase pro-inflammation cytokine IFN-γ and TNF-α release, and improve the proliferation activity of Jurkat T cells. Since GO-PEI-PEG targets the mouse liver effectively, the intrahepatic tumors in C57BL/6 mice are treated with GO-PEI-PEG/Pd-l1 siRNAs via the tail vein, resulting in shrinkage of the HCC tumors and boosting the anti-tumor efficacy in combination with oral sorafenib. A single treatment improves the total CD3+ and cytotoxic CD8+ T cell infiltration in the HCC tumor tissues and even spleen and upregulates the expression of Perforin, Gzmb, Ifng, Il-1b and Tnfa in the tumors after the combined treatment. Both the single and combined treatments enhance reactive oxygen species (ROS) accumulation, and improved HCC ferroptosis. The results suggest that GO-PEI-PEG delivered PD-L1 siRNAs combined with oral sorafenib can activate the adaptive immunity and tumor ferroptosis and reveal an effective therapy to treat advanced HCC patients.

Fabricating Black-Phosphorus/Iron-Tetraphosphide Heterostructure via a Solid-Phase Solution-Precipitation Method for High-Performance Nitrogen Reduction.

Although constructing heterostructures is considered as one of the most successful strategies to improve the activity of a catalyst, the heterostructures usually suffer from the cumbersome preparation treatments and low-yield. Inspired by a solid-phase solution-precipitation (SPSP) process, an approach for interface intensive heterostructures with high yield is developed. Herein, a black-phosphorus/iron-tetraphosphide (BP/FeP4 ) heterostructure is prepared mechanochemically with high transient pressure by the solid-phase ball milling approach. The BP/FeP4 heterostructure delivers excellent catalytic performance in the nitrogen reduction reaction (NRR) as exemplified by an NH3 yield of 77.6 µg h-1 mg cat . - 1 \[{\rm{mg}}_{{\rm{cat}}{\rm{.}}}^{{\bm{ - }}1}\] and Faradic efficiency of 62.9% (-0.2 V), which are superior to that of most NRR catalysts recently reported. Experimental investigation and density-functional theory calculation indicate the importance of excess phosphorus in the heterostructures on the NRR activity, which assists the Fe atom to activate N2 via adsorbing the H atom. The results demonstrate the great potential of this new type of heterostructures prepared by the SPSP approach. Benefiting from the simple preparation process and low cost, the heterostructures offer a new insight into the development of highly efficient catalysts.

Macroscale Superlubricity on Engineering Steel in the Presence of Black Phosphorus.

Friction and wear are the main reasons for decreasing the lifetime of moving mechanical components and causing energy loss. It is desirable to achieve macroscale superlubricity on industrial materials for minimizing friction. Herein, the two-dimensional material black phosphorus (BP) is prepared as an oil-based nanoadditive in oleic acid (OA) and shown to produce macroscale superlubricity at the steel/steel contact under high pressure. Experiments and molecular dynamics simulation reveal that BP quickly captures the carboxylic group and, as a result of the high contact pressure and heat, OA decomposes to release passivating species and recombines to form amorphous carbon giving rise to a composite solid tribofilm with BP. The OA and passivating groups adsorb onto the solid tribofilm to produce the passivating layer, thus resulting in macroscale superlubricity. The findings provide fundamental insight into the nature of tribochemical mechanisms and suggest a new approach to achieve macroscale superlubricity of industrial materials.

Near-infrared light II - assisted rapid biofilm elimination platform for bone implants at mild temperature.

Light-triggered therapy is a prospective method to combat implant-associated infection but near-infrared I (NIR-I) light has insufficient penetrating ability in tissues and local hyperthermia induced by the photothermal treatment may destroy surrounding healthy tissues. Herein, a near-infrared II (NIR-II) phototherapy system composed of upconversion elements doped titanium dioxide nanorods (TiO2 NRs)/curcumin (Cur)/hyaluronic acid (HA)/bone morphogenetic protein-2 (BMP-2) is designed for biomedical titanium and demonstrated to overcome the above hurdles simultaneously. Incorporation of F, Yb, and Ho not only improves the photocatalytic ability, but also renders the implants with the upconversion capability, so that the NRs can generate enough reactive oxygen species (ROS) when irradiated by the NIR-II laser. Furthermore, the combined actions of quorum sensing inhibitors, ROS, and physical puncture by NRs eliminate Staphylococcus aureus biofilms on titanium rapidly at a mild temperature of 45 °C by only requiring irradiation with the 1060 nm laser for only 15 min in vitro and in vivo. The presence of Cur mitigates the immune response and BMP-2 improves osteogenic differentiation, thus accelerating new bone formation. This low-temperature NIR-II light-triggered antibacterial platform has large potential in combating deep-tissue infection in clinical applications.

Sensitive and selective ctDNA detection based on functionalized black phosphorus nanosheets.

Circulating tumor DNA (ctDNA) identification is one of the most meaningful approaches towards early cancer diagnosis. However, effective and practical methods for analyzing this emerging class of biomarkers are still lacking. In this work, a biosensor based on nitrophenyl functionalized black phosphorus nanosheets (NP-BPs) is fabricated for sensitive and selective detection of ctDNA. In this work, a nitrophenyl functionalized black phosphorus nanosheets (NP-BPs) biosensor is fabricated for sensitive and selective detection of ctDNA. Due to the successful nitrophenyl functionalization, the NP-BPs biosensor shows higher quenching efficiency and stronger affinity towards single-stranded DNA (ssDNA), as compared with double-stranded DNA (dsDNA). Therefore, the NP-BPs biosensor exhibits 5.4-fold fluorescence enhancement when dye-labelled ssDNA probe forms dsDNA in the presence of its specific ctDNA target. This biosensor exhibits a detection limit of 50 fM and a wide linear detection range of 50 fM-80 pM, provides reliable readout in a short time (15 min). Moreover, the NP-BPs-based biosensor could be applied to discriminate single nucleotide polymorphisms in clinical serum samples. It is envisioned that the NP-BPs-based sensing platform has great potentials in early cancer diagnosis and monitoring cancer progression.

Mediated Drug Release from Nanovehicles by Black Phosphorus Quantum Dots for Efficient Therapy of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is an intractable disease involving a sticky mucus layer and nanoagents with mucus-penetrating capability offer a new way to deliver drugs. However, drug release from nanovehicles requires optimization to enhance the therapeutic effects of COPD therapy. Herein, black phosphorus quantum dots (BPQDs) are combined with PEGylated chitosan nanospheres containing the antibiotic amikacin (termed PEG@CS/BPQDs-AM NPs). As a drug-delivery system, the hydrophilicity of PEG and positive charge of CS facilitate the penetration of nanovehicles through the mucus layer. The nanovehicles then adhere to the mucous membrane. Furthermore, the BPQDs degrade rapidly into nontoxic PO43- and acidic H+ , thereby promoting the dissociation of PEGylated CS nanospheres, accelerating the release of AM, decreasing the vitality of biofilms for ease of eradication. Our results reveal that drug delivery mediated by BPQDs is a feasible and desirable strategy for precision medicine and promising for the clinical therapy of COPD.

Bioactive phospho-therapy with black phosphorus for in vivo tumor suppression.

Background and Purpose: Although inorganic nanomaterials have been widely used in multimodal cancer therapies, the intrinsic contributions of the materials are not well understood and sometimes underestimated. In this work, bioactive phospho-therapy with black phosphorus nanosheets (BPs) for in vivo tumor suppression is studied. Methods: Orthotopic liver tumor and acute myeloid leukemia are chosen as the models for the solid tumor and hematological tumor, respectively. BPs are injected into mice through the tail vein and tumor growth is monitored by IVIS bioluminescence imaging. Tumor tissues and serum samples are collected to determine the suppression effect and biosafety of BPs after treatment. Results: The in vitro studies show that BPs with high intracellular uptake produce apoptosis- and autophagy-mediated programmed cell death of human liver carcinoma cells but do not affect normal cells. BPs passively accumulate in the tumor site at a high concentration and inhibit tumor growth. The tumor weight is much less than that observed from the doxorubicin (DOX)-treated group. The average survival time is extended by at least two months and the survival rate is 100% after 120 days. Western bolt analysis confirms that BPs suppress carcinoma growth via the apoptosis and autophagy pathways. In addition, administration of BPs into mice suffering from leukemia results in tumor suppression and long survival. Conclusions: This study reveals that BPs constitute a type of bioactive anti-cancer agents and provides insights into the application of inorganic nanomaterials to cancer therapy.

A Hybrid Eukaryotic-Prokaryotic Nanoplatform with Photothermal Modality for Enhanced Antitumor Vaccination.

Cytomembrane-derived nanoplatforms are an effective biomimetic strategy in cancer therapy. To improve their functionality and expandability for enhanced vaccination, a eukaryotic-prokaryotic vesicle (EPV) nanoplatform is designed and constructed by fusing melanoma cytomembrane vesicles (CMVs) and attenuated Salmonella outer membrane vesicles (OMVs). Inheriting the virtues of the parent components, the EPV integrates melanoma antigens with natural adjuvants for robust immunotherapy and can be readily functionalized with complementary therapeutics. In vivo prophylactic testing reveals that the EPV nanoformulation can be utilized as a prevention vaccine to stimulate the immune system and trigger the antitumor immune response, combating tumorigenesis. In the melanoma model, the poly(lactic-co-glycolic acid)-indocyanine green (ICG) moiety (PI)-implanted EPV (PI@EPV) in conjunction with localized photothermal therapy with durable immune inhibition shows synergetic antitumor effects as a therapeutic vaccine. The eukaryotic-prokaryotic fusion strategy provides new perspectives for the design of tumor-immunogenic, self-adjuvanting, and expandable vaccine platforms.

Dual light-induced in situ antibacterial activities of biocompatibleTiO2/MoS2/PDA/RGD nanorod arrays on titanium.

Prevention of bacterial infection and promotion of osseointegration are two important issues for titanium (Ti) implants in medical research. In addition, after a biofilm is formed on the surface of implants, the immune system and antibiotic therapy may fail. In this work, bio-functionalized titanium dioxide (TiO2)/molybdenum disulfide (MoS2)/polydopamine (PDA)/arginine-glycine-aspartic acid (RGD) nanorod arrays (NAs) are prepared on Ti implants to not only kill bacteria noninvasively upon co-irradiation of 660 nm visible light (VL) and 808 nm near infrared (NIR) light, but also promote the osteogenic activity simultaneously. Dual light irradiation triggers the TiO2/MoS2 NA to generate hyperthermia and reactive oxygen species (ROS) in 10 min. The synergistic effects of the generated hyperthermia and ROS increase the bacterial membrane permeability and bacteria are killed rapidly and efficiently in vitro and in vivo. The biofilm is also eradicated and RGD on the nanorods improves cell adhesion, proliferation, and osteogenic differentiation. The strategy described here for the design of bio-functionalized coatings on Ti implants has great clinical potential in orthopedics, dentistry, and other medical fields.

Biodegradable Bi2 O2 Se Quantum Dots for Photoacoustic Imaging-Guided Cancer Photothermal Therapy.

As new 2D layered nanomaterials, Bi2 O2 Se nanoplates have unique semiconducting properties that can benefit biomedical applications. Herein, a facile top-down approach for the synthesis of Bi2 O2 Se quantum dots (QDs) in a solution is described. The Bi2 O2 Se QDs with a size of 3.8 nm and thickness of 1.9 nm exhibit a high photothermal conversion coefficient of 35.7% and good photothermal stability. In vitro and in vivo assessments demonstrate that the Bi2 O2 Se QDs possess excellent photoacoustic (PA) performance and photothermal therapy (PTT) efficiency. After systemic administration, the Bi2 O2 Se QDs accumulate passively in tumors enabling efficient PA imaging of the entire tumors to facilitate imaging-guided PTT without obvious toxicity. Furthermore, the Bi2 O2 Se QDs which exhibit degradability in aqueous media not only have sufficient stability during in vivo circulation to perform the designed therapeutic functions, but also can be discharged harmlessly from the body afterward. The results reveal the great potential of Bi2 O2 Se QDs as a biodegradable multifunctional agent in medical applications.

InSe Nanosheets for Efficient NIR-II-Responsive Drug Release.

Near-infrared-II (NIR-II) biowindow is appealing from the perspectives of larger maximum permissible exposure in comparison with the near-infrared-I biowindow, so the NIR-II-responsive drug-delivery nanoplatform is highly desirable. In this work, two-dimensional InSe nanosheets (InSe NSs) are modified with poly(ethylene glycol) and evaluated as an effective NIR-II-responsive cancer treatment nanoplatform. The InSe NSs synthesized by liquid exfoliation exhibit prominent NIR-II-responsive photothermal conversion efficiency (39.5%) and photothermal stability. Moreover, the InSe NSs have a doxorubicin (DOX) loading capacity as high as 93.6%, along with excellent NIR-II-responsive DOX release characteristic. The superior synergistic chemo/photothermal effects have also been demonstrated by the in vitro experiments in killing cancer cells. In combination with good biocompatibility, the InSe NSs have great potential in therapeutic applications.

Inherent Chemotherapeutic Anti-Cancer Effects of Low-Dimensional Nanomaterials.

Low-dimensional nanomaterials (LDNs) are receiving increasing attention in cancer therapy owing to their unique properties, especially the large surface area-to-volume ratio. LDNs such as metallic nanoparticles (NPs), hydroxyapatite NPs, graphene derivatives, and black phosphorus (BP) nanosheets have been proposed for drug delivery, photothermal/photodynamic therapies, and multimodal theranostic treatments. The therapeutic effectiveness is mainly based on the physical characteristics of LDNs, but their inherent bioactivity has not been fully capitalized. In this Minireview, recent advances in the anti-cancer effects of various types of LDNs with inherent chemotherapeutic bioactivity are described and the bioactivity mechanisms are discussed on the cellular and molecular levels. BP, one of the newest and exciting members of the LDN family, is highlighted owing to the excellent inherent bioactivity, selectivity, and biocompatibility in cancer therapy. LDNs and related derivatives possess inherent bioactivity and selective chemotherapeutic effects suggesting large potential as nanostructured anti-cancer agents in cancer therapy.

Biochar/struvite composite as a novel potential material for slow release of N and P.

For soil and environmental remediation, biochar/struvite composites are prepared by the crystallization-adsorption method. The recovery rates of N, P, and Mg in the solution increase to 99.02%, 97.23%, and 95.22%, respectively, by forming 10% biochar/struvite composite. X-ray diffraction (XRD) patterns acquired from the 10% biochar/struvite composite show a crystalline structure of MgNH4PO4·6H2O (PDF no. 15-0762) and release of the main nutrient elements (N, P, Mg) from the 10% biochar/struvite composite increases significantly compared to struvite. The solubility of the biochar/struvite composite is the highest in 0.5 mol/L HCl, second in 20 g/L citric acid, and lowest in water. The power function equation describes more precisely the cumulative release of N, P, and Mg from the biochar/struvite composite in distilled water, whereas it follows the simple Elovich equation in 20 g/L critic acid and first-order kinetics equation in 0.5 mol/L HCl. Leaching experiments are performed on the biochar/struvite composite in soil, and the results indicate that the biochar/struvite composite has a longer cycle of release of nutrients than traditional chemical fertilizers and has large potential as a slow-release fertilizer.

Black Phosphorus: Bioactive Nanomaterials with Inherent and Selective Chemotherapeutic Effects.

Black phosphorus nanosheets (BPs) are demonstrated to be highly bioactive anti-cancer agents because of their inherent and selective chemotherapeutic effects. Fast intracellular biodegradation of BPs and acute elevation of phosphate anions were observed from different types of cancer cells due to the stronger intracellular oxidative stress and accelerated energy metabolism, but normal cells are not affected. Selective biodegradation of BPs induced G2/M phase arrest and subsequent apoptosis- and autophagy-mediated cell death in cancer cells but not normal cells. The selectivity was superior to that of the traditional chemotherapeutic agent, doxorubicin (DOX). In vivo assessment confirmed the efficiency of BPs in suppressing tumor growth. This study provides insights into nanostructured bioactive anti-cancer agents and reveals a new direction for nanomedicine research.

Near-infrared light control of bone regeneration with biodegradable photothermal osteoimplant.

Mild heat stimulation can promote the restoration of bone defects but unfortunately, the delivery of exo-hyperthermy into human body is not efficient enough. In this study, mild heat-induced osteogenesis with high efficacy is demonstrated on an osteoimplant composed of black phosphorus nanosheets and poly(lactic-co-glycolic acid) (BPs@PLGA) with the participation of near-infrared (NIR) light irradiation. BPs@PLGA with only 0.2 wt% BPs show the highly-efficient NIR photothermal response even when being covered by a biological tissue as thick as 7 mm. In addition, this composite is completely biodegradable and the final degradation products are harmless H2O, CO2 and PO43- which can serve as necessary bone ingredient. The BPs@PLGA specimen mediated by low intensity and periodic NIR irradiation can effectively up-regulate the expressions of heat shock proteins and finally promote osteogenesis in vitro and in vivo. Boasting good biodegradability and NIR-mediated osteogenetic performances, the BPs@PLGA implant has great potential in orthopedic applications and this study provides new insights into the design and fabrication of new-style osteoimplants which can be remotely controlled.

Sequentially Triggered Delivery System of Black Phosphorus Quantum Dots with Surface Charge-Switching Ability for Precise Tumor Radiosensitization.

Cancer radiotherapy suffers from drawbacks such as radiation resistance of hypoxic cells, excessive radiation that causes damage of adjacent healthy tissues, and concomitant side effects. Hence, radiotherapy sensitizers with improved radiotherapeutic performance and requiring a relatively small radiation dose are highly desirable. In this study, a nanosystem based on poly(lactic- co-glycolic acid) (PLGA) and ultrasmall black phosphorus quantum dots (BPQDs) is designed and prepared to accomplish precise tumor radiosensitization. The PLGA nanoparticles act as carriers to package the BPQDs to avoid off-target release and rapid degradation during blood circulation. The nanosystem that targets the polypeptide peptide motif Arg-Gly-Asp-Gys actively accumulates in tumor tissues. The 2,3-dimethylmaleic anhydride shell decomposes in an acidic microenvironment, and the nanoparticles become positively charged, thereby favoring cellular uptake. Furthermore, glutathione (GSH) deoxidizes the disulfide bond of cystamine and sequentially triggers release of BPQDs, rendering tumor cells sensitive to radiotherapy. The treatment utilizing the PLGA-SS-D@BPQDs nanosystem and X-ray induces cell apoptosis triggered by overproduction of reactive oxygen species. In the in vivo study, the nanosystem shows excellent radiotherapy sensitization efficiency but negligible histological damage of the major organs. This study provides insights into the design and fabrication of surface-charge-switching and pH-responsive nanosystems as potent radiosensitizers to achieve excellent radiotherapy sensitization efficacy and negligible toxic side effects.