Weakly Acidic Microenvironment Research Articles

H2O2 Self‐Supplying CaO2/POM@MOF Bimodal Nanogeneration Materials for Photothermal and Chemodynamic Synergistic Antimicrobials

ABSTRACTThe emergence of bacterial resistance has a negative impact on the conventional antimicrobial treatments, and research into the development of the new antimicrobial materials is of great significance. Multimodal synergistic antimicrobial materials exert better antimicrobial effects compared with a single modality. In recent years, Polyoxometalate (POM) has shown great potential in the biomedical field due to its high catalytic activity and high photothermal conversion ability. However, owing to its small surface area, its applications have been greatly limited. Herein, we designed a H2O2 self‐supplied CDT and PTT bimodal nanogeneration material (i.e., CaO2/POM@MOF) possessing a larger surface area for the treatment of the bacterial infections, in which CaO2 could release O2 and H2O2 in the weakly acidic microenvironment of bacterial infection and the dual catalytic site of POM@MOF could enhance the CDT reaction to generate ROS, resulting in the bacterial oxidative stress and the leakage of the bacterial contents, and the exposure to the NIR light generates localized high temperature that cause the rupture of bacterial cell membranes and the denaturation of their proteins. Meanwhile, the superior stability of POM@MOF can release fewer metal ions to improve its biocompatibility. The in vitro antimicrobial experiments demonstrated that CaO2/POM@MOF possessed the combined CDT and PTT effect and exhibited excellent antimicrobial efficacy. This work presents a promising strategy to combat the bacterial infections.

Thermal-Responsive Antibacterial Hydrogel with Photothermal Therapy and Improving Wound Microenvironment for Promote Healing.

Skin damage is one of the most prevalent human injuries, which affects the health of human beings. However, skin damage is often accompanied by bacterial infection and wound microenvironment changes, causing damage to normal cells and inhibiting wound healing. Herein, we designed a thermal-responsive antibacterial hydrogel (GAG hydrogel) loaded with catalase (CAT)-like Au@Pt@MgSiO3 nanoparticles (APM NPs) and gentamicin (GM) to promote wound healing. The GAG hydrogel was used in a photothermal therapy (PTT)/antibiotic combination to kill bacteria, reduce the use of antibiotics, improve the wound microenvironment, promote cell proliferation, and accelerate wound healing. Under near-infrared laser irradiation, APM NPs in the hydrogel generated local hyperthermia to kill bacteria. Meanwhile, the generated heat led to a change in the hydrogel's morphology, enabling it to release GM and APM NPs to prevent the overuse of antibiotics. Subsequently, the CAT-like ability of the APM NPs decreased the oxidative stress caused by hydrogen peroxide (H2O2), thus remodeling the wound microenvironment. Then, the weakly acidic microenvironment of the wound caused the decomposition of the APM NPs and the release of magnesium ions (Mg2+), promoting the growth and migration of cells for wound healing. Therefore, the studied thermal-responsive antibacterial (GAG) hydrogel has potential in the field of wound healing.

A carboxymethyl-resistant starch/polyacrylic acid semi-IPN hydrogel with excellent adhesive and antibacterial properties for peri-implantitis prevention

Hydrogels possess inherent characteristics that render them promising for the prevention of peri-implantitis. Nonetheless, hydrogels with singular network structures are incapable of concurrently achieving the desired adhesion and mechanical properties. In this work, a carboxymethyl resistant starch/polyacrylic acid semi-interpenetrating (CMRS/PAA semi-IPN) hydrogel was successfully prepared in one step. Its morphology, structure, mechanical properties, and adhesion properties were systematically assessed, which revealed a homogeneously porous structure with a commendable mechanical strength of 67.317 kPa and an adhesion strength of 63 kPa. Ciprofloxacin (Cip) was loaded in the CMRS/PAA hydrogel via in situ compounding. The in vitro kinetic study of drug release shows that the slow drug release efficiency exceeds 90 % in the weakly acidic microenvironment at the infection site after 72 h, indicating enhanced antimicrobial properties. The Cip-loaded hydrogel also exhibits a remarkable bacterial inhibition rate exceeding 99 % against the pathogenic bacterium P. gingivalis and good cytocompatibility and hemocompatibility in vitro. In summary, the current work explored a novel solution and direction for the development of anti-infective medical materials applicable to dental implants.

Advancements in pH-Responsive nanoparticles for osteoarthritis treatment: Opportunities and challenges.

Osteoarthritis (OA) is a degenerative disease linked to aging and obesity. The global aging population has led to an increasing number of OA patients, imposing a significant economic burden on society. Traditional drugs treatment methods often fail to achieve satisfactory outcomes. With the rapid advancement of nanomaterial delivery systems, numerous studies have focused on utilizing nanomaterials as carriers to achieve efficient OA treatment by effectively loading and delivering bioactive ingredients (e.g., drugs, nucleic acids) tailored to the unique pathological conditions, such as the weakly acidic microenvironment of synovial fluid in OA patients. This review highlights the latest advancements in the use of pH-responsive nanoparticles for OA treatment, emphasizing the principle of targeted drug delivery leveraging the acidic microenvironment of inflamed joints. It further discusses the composition, synthesis, response mechanism, target selection, application, and recent research findings of nanoparticles, while also addressing the challenges and future directions in this promising field.

Targeting Bacterial Persisters via Reactive Oxygen Species‐Generating Hydrogel Microspheres

AbstractThe presence of bacterial persisters is a key factor contributing to chronic infection. However, no effective treatment methods are currently available. Thus, a platform is developed, called reactive oxygen species (ROS) bomb, based on microenvironment‐adaptive hydrogel microspheres, to oxidize the cell membranes of persisters in chronic periprosthetic joint infection (PJI). Fenton reagent hydroxy iron oxide (FeOOH) and a glucose oxidase (GOx)/calcium phosphate (CaP) acid‐responsive shell are sequentially induced on the surface of mesoporous polydopamine (PDA) nanoparticles by the PDA‐mediated ion precipitation and interfacial adhesion, followed by the coloaded with glucose into microfluidic hyaluronic acid hydrogel microspheres. Hydroxyl radicals are explosively generated through GOx‐mediated glucose oxidase, H2O2 production, and its Fenton‐like reactions with FeOOH, which also benefit from the weakly acidic microenvironment around persisters, result in the destruction of bacterial cell membrane, and subsequent overflow of cellular contents such as dsDNA, proteins, and K+. The bactericidal rates of methicillin‐resistant Staphylococcus aureus and Staphylococcus epidermidis persisters are up to 99.14% and 98.96%, and the bacterial loads in lesion location are significantly decreased after ROS bombs treated, effectively alleviated the inflammation and bone resorption damage. This work provides a new strategy toward persisters clearance and shows great application potential in other chronic infection‐related diseases.

Doxorubicin and iron-doped mesoporous silica nanoparticles for chemodynamic therapy and chemotherapy of breast cancer

This study depicts a simple and effective strategy for designing an intelligent drug delivery system activated by the tumor-specific weakly acidic microenvironment, offering a promising biotechnological platform for combined breast cancer treatment.

Tannic acid and carboxymethyl chitosan-based multi-functional double-layered hydrogel with pH-stimulated response behavior for smart real-time infection monitoring and wound treatment

The dramatic increase of drug-resistant pathogenic bacteria has seriously effect on human health, appealing the needs of developing theranostic platforms with stimuli-responsive materials to realize the accurate bacterial diagnostics and therapeutics. Herein, a tannic acid and carboxymethyl chitosan-based multifunctional ZIF-90@i-PPOPs-phenol red double-layered hydrogel with stimuli-responsiveness and antibacterial activity was fabricated. The inner layer hydrogel (ZIF-90@i-PPOPs-based TFC hydrogels) was fabricated based on ZIF-90@i-PPOPs, integrate tannic acid and carboxymethyl chitosan linked by formylphenylboronic acid (FPBA), which exhibited outstanding injectable, biodegradability and antibacterial activity. The outer layer hydrogel (PR@PAM hydrogels) were constructed from polyacrylamide (PAM) and pH indicator phenol red, owning porous structure and excellent tissue adhesion. Due to the weakly acidic microenvironment within wound, the inner-layer hydrogel was stimulus-responsively decomposed, resulting in the accurate delivery of the positively charged ZIF-90@i-PPOPs to the lesion site to capture and kill bacteria by enhanced Zn2+ and ROS release. Meantime, the outer-layer hydrogel could real-timely monitor the pH changes to evaluate the wound recovery status. These double-layered hydrogels possessed precisely pH monitoring capacity, excellent antibacterial ability and negligible side effect to normal tissue in vivo, implying the high potential of the suggested hydrogels as theranostic platform for antibacterial treatment.

Microenvironment Modulation of Ultrathin Bronze‐Phase TiO2 Nanosheets for Highly Selective Photocatalytic CO2 Reduction in Water

AbstractPhotocatalytic reduction of CO2 with H2O provides a promising and sustainable pathway to produce valuable chemicals and fuels. However, the low efficiency of CO2 reduction and the concomitant competition of H2 evolution pose serious challenges to practical applications. Herein, a novel approach is proposed to modulate the surface microenvironment of photocatalysts by utilizing hydrogen peroxide (H2O2). A bronze‐phase TiO2 (TB) composed of ultrathin nanosheet with a thickness of ∼3 nm is fabricated and employed as the model catalyst for photocatalytic CO2 reduction. H2O2 molecules are presumed to be bonded to the ultrathin TB surface to form the TB‐H2O2 (TBHO) active specie. The newly generated TBHO enhances the CO2 adsorption and accelerates mass transfer, and the weakly acidic microenvironment of the catalyst surface serves the purpose of mediating the proton‐coupled electron transfer path. Consequently, ultrathin TB nanosheets assisted by H2O2 show an excellent CO generation rate of 29.1 µmol−1 g−1 h−1 (which is 11.2‐fold higher than that of pure TB) in water, and the selectivity toward CO is nearly 100%. This work underscores the importance of tailoring the catalyst surface microenvironment to promote the CO2 reduction while minimizing the H2 generation in pure water.

Promoting effect of proanthocyanidin-amorphous calcium phosphate nanoparticles on biomimetic mineralization of demineralized dentin

Biomimetic mineralization is a new strategy for dentin repair emerging in the field of minimally invasive dentistry in recent years. However, the degradation of collagen fibrils and the lack of sustained supply of calcium and phosphorus ions are two main limitations during dentin biomimetic mineralization. Herein, by integrating the dual effects of collagen protection and mineralization induction, we proposed a novel nanoscale platform called proanthocyanidin-amorphous calcium phosphate nanoparticles (PA-ACP/NPs), which were solid nanospheres with uniform size and good biocompatibility, and could continuously release Ca and P ions in neutral or weak acidic microenvironment. PA-ACP/NPs effectively decreased the endogenous collagenase activity of demineralized dentin matrix and protected demineralized dentin collagen from degradation. Compared with the control ACP/NPs, PA-ACP/NPs induced nearly complete intrafibrillar mineralization of collagen fibrils and facilitated remineralization of demineralized dentin. As an additive of dental adhesives for the preliminary exploration of clinical application forms, the adhesive containing 20 wt% PA-ACP/NPs induced biomimetic intrafibrillar mineralization within the bonding interface after one and three months. PA-ACP/NPs nanoscale delivery exhibits excellent effects on stabilizing collagen fibrils and provides a long-term supply of mineral ions for dentin biomimetic mineralization, being a promising strategy for dentin biomimetic repair.

In situ formation of ferrous sulfide in glycyrrhizic acid hydrogels to promote healing of multi-drug resistant Staphylococcus aureus-infected diabetic wounds

Diabetic wound treatment faces great challenges in clinic. Staphylococcus aureus (S. aureus) is one of the most frequently isolated pathogens from the diabetic infections, which can severely impede wound healing time. Herein, ferrous sulfide (FeS) nanoparticles were fabricated through an in situ reaction between Fe2+ and S2− in glycyrrhizic acid (GA) solution. As the FeS nanoparticles aged, the solution gradually transformed into a gel, exhibiting excellent mechanical strength, injectability, and biocompatibility as a wound dressing. In addition to its own pharmacological effects, GA could act as the protector for FeS from oxidation of air. It also provided a weak acidic microenvironment, facilitating the pH-dependent dissolution reaction of FeS to release H2S and Fe2+. Notably, the effective antibacterial performance of the FeS/GA hydrogels towards S. aureus and multi-drug resistant S. aureus (MRSA) was achieved via the degradedly released Fe2+ and H2S through combination of ferroptosis damage and energy metabolism disruption. Moreover, FeS/GA hydrogels effectively modulated the proportion of M1/M2 macrophages, reduced the secretion of inflammatory cytokines, and significantly enhanced the proliferation and migration of fibroblasts in vitro. Importantly, in an MRSA-infected diabetic wound model, the FeS/GA hydrogels efficiently eradicated bacteria and regulated the inflammatory microenvironment, thereby promoting the diabetic wound repair. Overall, our study establishes a novel strategy for developing multifunctional hydrogels that serve as an effective therapeutic platform for managing bacteria-infected diabetic wounds.

Poly(l-Ornithine)-Based Polymeric Micelles as pH-Responsive Macromolecular Anticancer Agents.

Anticancer peptides and polymers represent an emerging field of tumor treatment and can physically interact with tumor cells to address the problem of multidrug resistance. In the present study, poly(l-ornithine)-b-poly(l-phenylalanine) (PLO-b-PLF) block copolypeptides were prepared and evaluated as macromolecular anticancer agents. Amphiphilic PLO-b-PLF self-assembles into nanosized polymeric micelles in aqueous solution. Cationic PLO-b-PLF micelles interact steadily with the negatively charged surfaces of cancer cells via electrostatic interactions and kill the cancer cells via membrane lysis. To alleviate the cytotoxicity of PLO-b-PLF, 1,2-dicarboxylic-cyclohexene anhydride (DCA) was anchored to the side chains of PLO via an acid-labile β-amide bond to fabricate PLO(DCA)-b-PLF. Anionic PLO(DCA)-b-PLF showed negligible hemolysis and cytotoxicity under neutral physiological conditions but recovered cytotoxicity (anticancer activity) upon charge reversal in the weakly acidic microenvironment of the tumor. PLO-based polypeptides might have potential applications in the emerging field of drug-free tumor treatment.

Display of CCL21 on cancer cell membrane through genetic modification using a pH low insertion peptide

CCL21, a secondary lymphoid tissue chemokine, plays an important role in generating an effective anti-tumor immune response. In this study, a genetically modified CCL21 was developed by inserting a pH low insertion peptide to establish a CCL21-rich microenvironment for tumors. The fusion tag thioredoxin (Trx) was designed and fused at the N-terminal of the recombinant protein to protect it from being irrevocably misfolded in microbial host cells. The prokaryotic expression vector pET32a-CCL21-pHLIP was constructed and successfully expressed in E. coli BL21 (DE3) with a soluble expression form and a molecular weight of ~35 kDa. The induction conditions were optimized to obtain an extremely high yield of 6.7 mg target protein from 31.1 mg total protein. The 6xHis tagged Trx-CCL21-pHLIP was purified using Ni-NTA resin, and it was confirmed using SDS-PAGE and Western blot analyses. Consequently, the Trx-CCL21-pHLIP protein was successfully displayed on the cancer cell surface in a weak acidic microenvironment and showed the same ability as CCL21 in recruiting CCR7-positive cells. Additionally, the CCL21 fusion protein with or without Trx tag showed similar functions. Therefore, the study implies the feasibility of directing a modular genetic method for the development of protein-based drugs.

Weakly acidic microenvironment of the wound bed boosting the efficacy of acidic fibroblast growth factor to promote skin regeneration.

The pH value within the wound microenvironment influences indirectly and directly all biochemical reactions taking place in the process of skin wound healing. Currently, it is generally believed that a low pH value, such as it is found on normal skin, is favorable for wound regeneration, while some investigations have shown that in fact alkaline microenvironments are required for some healing processes. The role of growth factors in promoting wound healing requires a specific microenvironment. In wound microenvironments of different pH, growth factors with different isoelectric points may have different effects. To explore whether the application of FGF with different isoelectric points in wounds with different pH values interferes with the healing process to different degrees, GelMA hydrogels with different pH values were prepared to maintain the wounds microenvironment with the same pH values, in which aFGF and bFGF were loaded as well. The results show that GelMA hydrogels of different pH values maintained the same pH of the wound microenvironment sustainably on the 4th day. Moreover, aFGF and bFGF promoted skin wound healing to varying degrees in different pH wound microenvironments. In particular, aFGF significantly promoted wound re-epithelialization in a weak acidic microenvironment, while bFGF promoted collagen synthesis and deposition in the early stage of weak acid wounds. In addition, aFGF plays a superior role in inhibiting inflammation in weak acidic wounds.

Degradable iron-rich mesoporous dopamine as a dual-glutathione depletion nanoplatform for photothermal-enhanced ferroptosis and chemodynamic therapy

Glutathione (GSH) is a crucial factor in limiting the effects of chemodynamic therapy (CDT) and ferroptosis, an iron-based cell death pathway. Based on this, we constructed iron-rich mesoporous dopamine (MPDA@Fe) nanovehicles with a dual-GSH depletion function by combining MPDA and Fe. Poly (ethylene glycol) (PEG) was further modified to provide desirable stability (PM@Fe) and glucose oxidase (GOx) was grafted onto PM@Fe (GPM@Fe) to address the limitation of hydrogen peroxide (H2O2). After the nanoparticles reached the tumor site, the weakly acidic microenvironment promoted the release of Fe. Then FeII reacted with H2O2 to generate hydroxyl radical (OH) and FeIII. The generated FeIII was reduced to FeII by GSH, which circularly participated in the Fenton reaction and continuously produced tumor inhibitory free radicals. Meanwhile, GOx consumed glucose to provide H2O2 for the reaction. MPDA had also been reported to deplete GSH. Therefore, dual consumption of GSH led to the destruction of intracellular redox balance and inhibition of glutathione-dependent peroxidase 4 (GPX4) expression, resulting in an increase in lipid peroxides (LPO) and further induction of ferroptosis. Additionally, MPDA-mediated photothermal therapy (PTT) raised the temperature of tumor area and produced photothermal-enhanced cascade effects. Hence, the synergistic strategy that combined dual-GSH depletion-induced ferroptosis, enhanced CDT and photothermal cascade enhancement based on MPDA@Fe could provide more directions for designing nanomedicines for cancer treatment.

Local pH mapping in the cell adhesion nano-interfaces on a pH-responsive fluorescence-dye-immobilized substrate.

Cell-substrate adhesion nano-interfaces can, in principle, exhibit a spatial distribution of local pH values under the influence of the weakly acidic microenvironment of glycocalyx grafted on lipid bilayer cell membrane which is compressed and closely attached to culture substrate in the vicinity of integrin-adhesion complexes. However, a simple local pH distribution imaging methodology has not been developed. In this study, to visualize the local pH distribution at the cell adhesion interface, we prepared glass substrates chemically modified with a pH-responsive fluorescent dye fluorescein isothiocyanate (FITC), observed the distribution of FITC fluorescence intensity at the adhesion interface of fibroblast (NIH/3T3) and cancer cells (HeLa), and compared the FITC images with the observed distribution of focal adhesions. FITC images were converted to pH mapping based on the pH-fluorescence calibration data of surface-immobilized FITC pre-measured in different pH media, which showed significantly larger regions with lowered pH level (6.8-7.0) from outside the cell (pH 7.4) were observed at the thick inner periphery of HeLa cells while 3T3 cells exhibited smaller lowered pH regions at the thin periphery. The lowered pH regions overlapped with many focal adhesions, and image analysis showed that larger focal adhesions tend to possess more lowered pH sites inside, reflecting enhanced glycocalyx compression due to accumulated integrin-adhesion ligand binding. This tendency was stronger for HeLa than for 3T3 cells. The role of glycocalyx compression and the pH reduction at the cell adhesive interface is discussed.

Hyaluronic acid targeted and pH-responsive multifunctional nanoparticles for chemo-photothermal synergistic therapy of atherosclerosis.

Atherosclerosis is a global disease with an extremely high morbidity and fatality rate, so it is necessary to develop effective treatments to reduce its impact. In this work, we successfully prepared a multifunctional drug-loaded nano-delivery system with pH-responsive, CD44-targeted, and chemical-photothermal synergistic treatment. Dendritic mesoporous silica nanoparticles capped with copper sulfide (CuS) were synthesized via an oil-water biphase stratification reaction system; these served as the carrier material and encapsulated the anticoagulant drug heparin (Hep). The pH-sensitive Schiff base bond was used as a gatekeeper and targeting agent to modify hyaluronic acid (HA) on the surface of the nanocarrier. HA coating endowed the nanocomposite with the ability to respond to pH and target CD44-positive inflammatory macrophages. Based on this multifunctional nanocomposite, we achieved precise drug delivery, controlled drug release, and chemical-photothermal synergistic treatment of atherosclerosis. The in vitro drug release results showed that the nanocarriers exhibited excellent drug-controlled release properties, and could release drugs in the weakly acidic microenvironment of atherosclerotic inflammation. Cytotoxicity and cell uptake experiments indicated that nanocarriers had low cytotoxicity against RAW 264.7 cells. Modification of HA to nanocarriers can be effectively internalized by RAW 264.7 cells stimulated by lipopolysaccharide (LPS). Combining CuS photothermal treatment with anti-atherosclerosis chemotherapy showed better effects than single treatment in vitro and in vivo. In summary, our research proved that H-CuS@DMSN-NC-HA has broad application prospects in anti-atherosclerosis.

Highly selective separation of acteoside from Cistanche tubulosa using an ionic liquid based aqueous two–phase system

To achieve simple and efficient separation of acteoside (ACT), extraction ACT from crude extracts of Cistanche tubulosa via ionic liquid (IL) based aqueous two-phase system (ATPS) is investigated. The IL–ATPS comprising [C4mim]BF4 and (NH4)2SO4 exhibits excellent extraction performance, extracting almost all ACT in the [C4mim]BF4-rich phase. The high polarity of [C4mim]BF4 having multi-hydrogen bond receptors is conducive for extracting ACT in the IL-rich phase, and (NH4)2SO4 not only provides a weak acidic microenvironment for increasing ACT stability in the IL-rich phase but also reduces the solubility of ACT in the salt-rich phase via the salting-out effect. In addition, molecular simulation results show that ACT is extracted in the [C4mim]BF4-rich phase via multi-interactions, including hydrogen bonding, van der Waals forces, and π–π stacking. This study is expected to provide a valuable reference for the separation of bioactive constituents from natural products.

A novel weak acid activated probe for highly selective monitoring selenocysteine in living cells

Selenocysteine (Sec, pKa 5.8) is genetically encoded 21st amino acid into the active site of selenoproteins, which have broad functions relevant to various diseases, tissues or organs and subcellular organelles. However, many selenoproteins involved cellular functions still remains unclear. In addition, since biothiols such as glutathione (GSH, pKa 8.3), possessing similar chemical properties with Sec, commonly exist in living systems at high levels. Thus, it is of great importance and high challenge to identify novel probes for selectively monitoring Sec over biothiols. In this paper, we proposed a smart strategy which allowed us to develop a lysosome targetable probe for specifically sensing Sec. By restricting weak acidic microenvironment, the probe shows a specific detection for Sec with 85-fold fluorescence enhancement owing to the remaining high activity of Sec at pH 5.0. Moreover, being low cytotoxicity to the cells verified by MTS assay, the probe was then successfully applied for imaging exogenous and endogenous Sec in lysosomes, indicating its potential for the biological investigation of Sec in subcellular organelles.

A Facile Approach to Carbon Dots‐Mesoporous Silica Nanohybrids and Their Applications for Multicolor and Two‐Photon Imaging Guided Chemo‐/Photothermal Synergistic Oncotherapy

AbstractMultifunctional nanocarrier‐based theranostics have been proposed to overcome some key problems in cancer treatments. In this contribution, a facile approach is reported to synthesize carbon dots‐mesoporous silica nanohybrids (named MSNs‐CDs) via a one‐pot microwave heating reaction of amino‐functionalized mesoporous silica nanoparticles (MSNs‐NH2) and citric acid in formamide. The MSNs‐CDs nanohybrids exhibit capabilities of multicolor/two‐photon imaging, high photothermal conversion under NIR laser irradiation (671 nm), and anti‐cancer drug delivery, and thus could potentially be applied as a multifunctional nanocarrier‐based theranostic agent for cancer. Further studies revealed that CDs were in situ formed on the surface of MSNs during the reaction, which is amenable for the observed multicolor/two‐photon imaging and photothermal properties. Besides, the well‐preserved MSNs characters of MSNs‐CDs nanohybrids (e. g., mesoporous structure, large surface area and pore volume) enable them to be an ideal nanocarrier for delivering anti‐cancer drugs, such as doxorubicin (DOX). Importantly, the MSNs‐CDs@DOX exhibited pH‐ (lower pH being preferred) and thermo‐responsive DOX release behaviors, which would effectively decrease side effects and meanwhile enhance the efficacy of chemotherapy due to the weak acidic microenvironment of tumor and photothermal effect of the CDs. Finally, in vitro experiments exhibited that the highest therapeutic efficacy was obtained by MSNs‐CDs@DOX with NIR irradiation, attributing to the synergistic effect of chemotherapy and PTT. This study not only provides a facile method to prepare CDs and MSNs nanohybrids, but also demonstrates that both of the superior features and functions of CDs and MSNs could be preserved and combined, which are deemed to be beneficial for the development of multifunctional theranostic nanoplatform for cancers.

Ultrasound-responsive polymersomes capable of endosomal escape for efficient cancer therapy

Stimuli-responsive anticancer drug delivery vehicles have attracted increasing attention in nanomedicine. However, controlled drug release in vivo is still an important challenge, as traditional stimuli lack maneuverability. To solve this problem, we designed an ultrasound and pH-responsive polymersome by self-assembly of poly(ethylene oxide)-block-poly(2-(diethylamino)ethyl methacrylate)-stat-poly(methoxyethyl methacrylate) [PEO-b-P(DEA-stat-MEMA)], where PEO acts as the corona-forming block, DEA acts as the endosomal escape segment, and MEMA acts as the ultrasound-responsive segment. This strategy combines the advantages of noninvasive ultrasonic stimulus which can be applied from outside to any organ regardless of depth, and the weakly acidic microenvironment of tumor tissue. In vitro experiments confirmed excellent endosomal escape ability, on-demand drug release behavior, low cytotoxicity, and high intracellular delivery efficiency of polymersomes. In vivo antitumor tests revealed that in the presence of sonication, the anticancer drug was released at an accelerated rate from these ultrasound-responsive polymersomes, and the DOX-loaded polymersomes + sonication group significantly inhibited tumor growth (95% reduction in tumor mass) without any side effects. Overall, this ultrasound-responsive polymersome provides us with a fresh insight into designing next-generation stimuli-responsive drug carriers with better maneuverability and higher chemotherapeutic efficiency.