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Cancer cell‐triggered sol–gel transformation of mineralized hydrogel (PAA‐MnO2) is designed as a facile strategy for cancer detection by manipulating the mineralization process in the presence of cancer cells. The mineralization of polyacrylic acid (PAA) with calcium phosphate via carboxyl‐Ca2+ complex is initially inhibited by the incorporation of reactive oxygen species (ROS)‐sensitive manganese oxide (MnO2) with polymer dots (PDs). In this system, the mineralization can be induced after cleaving MnO2 into Mn2+ by high ROS levels in cancer cells, forming a PAA‐MnO2 mineralized hydrogel and resulting in a naked‐eye system for cancer monitoring. Naked‐eye monitoring of ROS‐responsive sol–gel transformation is performed using a circulator device containing circulating cells to discriminate cancer (HeLa, PC‐3, B16F10) from normal cells (CHO‐K1). With the incorporation of PDs, PAA‐MnO2 mineralized hydrogel not only provides physical transformation (stretchability, viscosity) but also fluorescence‐recovery and electroconductivity changes at different cancer‐cell concentrations (104–106 cells mL−1), including distinct strain–pressure responses that can be wirelessly monitored via smartphones. Furthermore, in vivo, experiments suggest that PAA‐MnO2 mineralized hydrogel can be formed in tumor‐bearing mice owing to its excellent ROS‐scavenging activity at the tumor site, as confirmed by SOD2 and gene‐expression analysis. Thus, this unique approach can potentially enable simple and effective cancer detection in future point‐of‐care diagnostics. [ABSTRACT FROM AUTHOR]

Small interfering RNA (siRNA) therapeutics, characterized by high specificity, potency, and durability, hold great promise in the treatment of cancer and other diseases. However, the clinic implementation of siRNA therapeutics critically depends on the safe and on–demand delivery of siRNA to the target cells. Here, we reported a family of ferrocenyl amphiphilic dendrimers (Fc-AmDs) for on–demand delivery of siRNA in response to the high ROS content in cancer cells. These dendrimers bear ROS–sensitive ferrocene moieties in the hydrophobic components and positively chargeable poly(amidoamine) dendrons as the hydrophilic entities, possessing favorable safety profiles and ROS responsive properties. One of these ferrocenyl amphiphilic dendrimers, Fc-C8-AmD 8A, outperforms in siRNA delivery, benefiting from its optimal balance of hydrophobicity and hydrophilicity. Its ROS feature facilitates specific and efficient disassembly of its complex with siRNA in ROS–rich cancer cells for effective siRNA delivery and gene silencing. Moreover, Fc-C8-AmD 8A also integrates the features and beneficial properties of both lipid and dendrimer vectors. Therefore, it represents a novel on–demand delivery system for cancer cell–specific siRNA delivery. This work opens new perspectives for designing self–assembly nanosystems for on–demand drug delivery. [ABSTRACT FROM AUTHOR]

Sorafenib is a first-line drug for liver cancer treatment, but its clinical efficacy is still limited by drawbacks such as drug tolerance, toxic effects, and low bioavailability. Therefore, it is urgent to find efficient ways to synergize sorafenib with other agents and increase its bioavailability in order to enhance its clinical efficacy. Herein, we report the successful development of a carrier-free nanoplatform of an artesunate prodrug to potentiate the efficacy of sorafenib against hepatocellular carcinoma. The artesunate prodrug was synthesized by conjugating artesunate and linoleic acid through a thioketone (TK) bond. This prodrug can self-assemble in an aqueous solution via a one-step precipitation method. Furthermore, the inclusion of sorafenib during the self-assembly process results in a carrier-free artesunate/sorafenib mixed nanomedicine (SA@NPs) with a uniform and stable particle size. In addition, SA@NPs possess ROS-responsive drug-releasing ability by breaking up thioketone bonds under high H2O2 levels in tumors. The synergistic anticancer effects of SA@NPs have been demonstrated both in vivo and in vitro. SA@NPs can achieve significantly enhanced synergetic ferroptosis of tumor cells and show potentiated sorafenib efficacy against hepatocellular carcinoma. Moreover, SA@NPs have a tumor inhibition rate of 84.2%, which is 1.63-, 4.22-, and 1.29-fold higher than that in the experimental groups treated with free sorafenib, artesunate, and the simplified combined medication of sorafenib/artesunate, respectively. Overall, this work presents a significant advancement in the clinical chemotherapy of liver cancer and may pave the way for promising developments in the compatibility and clinical combination application of traditional Chinese medicine.

Small interfering RNA (siRNA) therapeutics, characterized by high specificity, potency, and durability, hold great promise in the treatment of cancer and other diseases. However, the clinic implementation of siRNA therapeutics critically depends on the safe and on–demand delivery of siRNA to the target cells. Here, we reported a family of ferrocenyl amphiphilic dendrimers (Fc-AmDs) for on–demand delivery of siRNA in response to the high ROS content in cancer cells. These dendrimers bear ROS–sensitive ferrocene moieties in the hydrophobic components and positively chargeable poly(amidoamine) dendrons as the hydrophilic entities, possessing favorable safety profiles and ROS responsive properties. One of these ferrocenyl amphiphilic dendrimers, Fc-C8-AmD 8A, outperforms in siRNA delivery, benefiting from its optimal balance of hydrophobicity and hydrophilicity. Its ROS feature facilitates specific and efficient disassembly of its complex with siRNA in ROS–rich cancer cells for effective siRNA delivery and gene silencing. Moreover, Fc-C8-AmD 8A also integrates the features and beneficial properties of both lipid and dendrimer vectors. Therefore, it represents a novel on–demand delivery system for cancer cell–specific siRNA delivery. This work opens new perspectives for designing self–assembly nanosystems for on–demand drug delivery.

Abstract Resolvin D1 (RvD1) has been shown to provide effective protection against ischemia–reperfusion injury in multiple vital organs such as the heart, brain, kidney. However, the clinical translational potential of systemic administration of RvD1 in the treatment of ischemia–reperfusion injury is greatly limited due to biological instability and lack of targeting ability. Combining the natural inflammatory response and reactive oxygen species (ROS) overproduction after reperfusion injury, we developed a platelet-bionic, ROS-responsive RvD1 delivery platform. The resulting formulation enables targeted delivery of RvD1 to the injury site by hijacking circulating chemotactic monocytes, while achieving locally controlled release. In a mouse model of myocardial ischemia repefusuin (MI/R) injury, intravenous injection of our formula resulted in the enrichment of RvD1 in the injured area, which in turn promotes clearance of dead cells, production of specialized proresolving mediators (SPMs), and angiogenesis during injury repair, effectively improving cardiac function. This delivery system integrates drug bio-protection, targeted delivery and controlled release, which endow it with great clinical translational value.

Resolvin D1 (RvD1) has been shown to provide effective protection against ischemia–reperfusion injury in multiple vital organs such as the heart, brain, kidney. However, the clinical translational potential of systemic administration of RvD1 in the treatment of ischemia–reperfusion injury is greatly limited due to biological instability and lack of targeting ability. Combining the natural inflammatory response and reactive oxygen species (ROS) overproduction after reperfusion injury, we developed a platelet-bionic, ROS-responsive RvD1 delivery platform. The resulting formulation enables targeted delivery of RvD1 to the injury site by hijacking circulating chemotactic monocytes, while achieving locally controlled release. In a mouse model of myocardial ischemia repefusuin (MI/R) injury, intravenous injection of our formula resulted in the enrichment of RvD1 in the injured area, which in turn promotes clearance of dead cells, production of specialized proresolving mediators (SPMs), and angiogenesis during injury repair, effectively improving cardiac function. This delivery system integrates drug bio-protection, targeted delivery and controlled release, which endow it with great clinical translational value. [ABSTRACT FROM AUTHOR]

Poly-ion complex (PIC) integrating non-antibiotic theranostics holds great promise in the combat against drug-resistant bacteria. Photosensitizers with aggregation-induced emission (AIE) characteristic are particularly intriguing theranostic agents, but incorporating them into antibacterial PIC to enable both fluorescence and reactive oxygen species (ROS) generation turn-on deems a great challenge. Here we report the development of a PIC that can dually boost the fluorescence and ROS generation in the presence of pathogen bacteria. The PIC is constructed based on an anionic polydiacetylene poly(deca-4,6-diynedioic acid) (PDDA), which completely degrades in the presence of ROS. A cationic polymer quaternized poly(2-(dimethylamino)ethyl methacrylate) (PQDMA) that can disrupt bacterial membrane is co-loaded together with a highly efficient AIE photosensitizer TPCI in the PIC. PIC is nonfluorescent initially in that PDDA can quench the AIE of TPCI in PIC. When pathogenic bacteria are present, they can disturb the assembly of PIC to release TPCI, the fluorescence of which turns on sensitively to indicate the existence of bacteria. The on-demand irradiation can be subsequently applied to excite TPCI, which generates ROS to degrade PDDA and deform the PIC. As a result, TPCI and PQDMA are completely released to eliminate bacteria through a synergy of turned-on photodynamic therapy (PDT) and membrane disruption. The highly efficient detection and inhibition against both Gram-negative and Gram-positive bacteria have validated this polydiacetylene-based PIC system as an effective non-antibiotic antibacterial theranostic platform as well as a new strategy to enable "turn-on" fluorescence sensing and imaging of AIE fluorophores. [ABSTRACT FROM AUTHOR]

Heart failure (HF) represents the terminal stage of numerous cardiovascular disorders and lacks effective therapeutic strategies. The accumulation of senescent cardiomyocytes is a cardinal characteristic of HF, contributing to myocardial dysfunction and deteriorating the myocardial microenvironment through the development of senescence-associated secretory phenotypes (SASPs), ultimately culminating in pathological remodeling. Senolytics, a promising therapeutic strategy that selectively induces apoptosis in senescent cells, faces challenges due to nonspecific effects, raising concerns for clinical implementation. In this study, we developed peptide-amphiphilic nanoassemblies as responsive drug navigators for targeted delivery. The modular nanoassemblies comprise a hydrophilic domain containing a CD9-binding peptide, a hydrophobic domain incorporating a reactive oxygen species (ROS)-responsive motif, and an alkyl tail for encapsulation of the senolytic ABT263. The CD9-targeted and ROS-responsive nanoassemblies (AP@ABT263) specifically recognized senescent cardiomyocytes and modulated the release of ABT263 in the presence of elevated intracellular ROS levels. AP@ABT263 treatment significantly enhanced the targeted delivery of ABT263 to senescent cells in both in vitro and in vivo while showing minimal toxicity to normal cardiomyocytes and other tissues. Our findings provide compelling evidence that AP@ABT263 efficiently eradicated senescent cardiomyocytes, enhanced cardiac function, and attenuated the deleterious effects of SASP, thereby preventing adverse cardiac remodeling. In summary, AP@ABT263 represents a highly promising approach for responsive and controlled drug release in senescent cardiomyocytes, providing valuable insights into the development of intelligent pharmaceutical interventions for the management of HF.

The applications of amino acid-based polymers are impeded by their limited structure and functions. Herein, a small library of methionine-based polymers (Met-P) with programmed structure and reactive oxygen species (ROS)-responsive properties is developed for tumor therapy. The Met-P can self-assemble into sub-100 nm nanoparticles (NPs) and effectively load anticancer drugs (such as paclitaxel (PTX) (P@Met-P NPs)) via the nanoprecipitation method. The screened NPs with superior stability and high drug loading are further evaluated in vitro and in vivo. When encountering with ROS, the Met-P polymers will be oxidized and then switch from a hydrophobic to a hydrophilic state, triggering the rapid and self-accelerated release of PTX. The in vivo results indicated that the screened P@2Met10 NPs possessed significant anticancer performance and effectively alleviated the side effects of PTX. More interestingly, the blank 2Met10 NPs displayed an obvious self-tumor inhibiting efficacy. Furthermore, the other Met-P NPs (such as 2Met8, 4Met8, and 4Met10) are also found to exhibit varied self-anti-cancer capabilities. Overall, this ROS-responsive Met-P library is a rare anticancer platform with hydrophobic/hydrophilic switching, controlled drug release, and self-anticancer therapy capability., (© 2024 Wiley‐VCH GmbH.)

• Natural polyphenol conjugated prodrug hydrogels were designed for prevention of peritendinous adhesion. • The prodrug strategy using ROS-responsive bridging linker exhibited targeted aggregation toward the high ROS region. • The hydrogel could reduce the clinical adhesion scores of peritendinous adhesion by 3–4 grades. The bidirectional regulations of antiadhesion and regeneration are crucial for Achilles tendon injuries. However, the precise prevention and treatments of peritendinous adhesions both in time and space are still great challenges. Here, a series of time–space regulating prodrug (tannic acid (TA), epigallocatechin (EGC) and epigallocatechin gallate (EGCG)) hydrogels are designed for the prevention of peritendinous adhesion in Achilles tendon contusion and rupture injuries. In the term of space, the self-healing and deformable hydrogels prepared by crosslinking phenylboric acid (PBA) functionalized polyphosphazene (PZBA) with guar gum (GG) through ROS-responsive phenylborate ester (PBAE) can specifically aggregate to the high ROS sites via the ROS-responsive degradation and recombination of PBAE. Thus, providing support and acting as barriers to inhibit fibroblast proliferation. In the term of time, the prodrug strategy using ROS-responsive PBAE as bridging linker can achieve long-term anti-inflammatory effect over 2 weeks. Furthermore, the degradation time of hydrogels matched the course of peritendinous adhesion, thus achieved bidirectional regulations (decrease the gene expression of TGF-β1, COL-1 and COL-3 to antiadhesion in the early stage but increase them to promote regeneration in the late stage). This study presents a promising approach employing smart prodrug hydrogels with time–space regulating properties for prevention of peritendinous adhesion. [ABSTRACT FROM AUTHOR]

Membranous nephropathy (MN) is a common immune-mediated glomerular disease that requires the development of safe and highly effective therapies. Celastrol (CLT) has shown promise as a therapeutic molecule candidate, but its clinical use is currently limited due to off-target toxicity. Given that excess levels of reactive oxygen species (ROS) contributing to podocyte damage is a key driver of MN progression to end-stage renal disease, we rationally designed ROS-responsive cationic polymeric nanoparticles (PPS-CPNs) with a well-defined particle size and surface charge by employing poly(propylene sulfide)-polyethylene glycol (PPS-PEG) and poly(propylene sulfide)-polyethylenimine (PPS-PEI) to selectively deliver CLT to the damaged glomerulus for MN therapy. Experimental results show that PPS-CPNs successfully crossed the fenestrated endothelium, accumulated in the glomerular basement membrane (GBM), and were internalized by podocytes where rapid drug release was triggered by the overproduction of ROS, thereby outperforming nonresponsive CLT nanotherapy to alleviate subepithelial immune deposits, podocyte foot process effacement, and GBM expansion in a rat MN model. Moreover, the ROS-responsive CLT nanotherapy was associated with significantly lower toxicity to major organs than free CLT. These results suggest that encapsulating CLT into PPS-CPNs can improve efficacy and reduce toxicity as a promising treatment option for MN.

Although nanomedicines can passively target tumor through the enhanced permeability and retention (EPR) effect, their distribution and retention are limited by complex tumor microenvironment. Herein, a self-delivery supra -- molecular nanoplatform with shape-transforming capacity (Ce6-CD/ Fc-pep-PEG) is constructed by the host-guest interaction between chlorin e6- conjugated β-cyclodextrin (Ce6-CD) and ferrocene-modified FFVLG3C-PEG conjugates (Fc-pep-PEG). Following passive accumulation mediated by the EPR effect, hydrophobic Fc is oxidized to water-soluble Fc+ by endogenous ROS in tumor sites. The resulting Fc+-pep-PEG fragment dissociated from Ce6-CD and recombined to nanofibers through the intermolecular hydrogen bonds among FFVLG3C peptide chains, thus enhancing the retention. Meanwhile, the Ce6-CD fragment still maintained the form of spherical micelles with a relatively smaller size to penetrate into the deep tumor regions. Moreover, the cascade Fenton reaction catalyzed by Fc generated •OH and O2 to relieve hypoxia and amplify PDT efficiency. In turn, ROS generated by PDT promoted shape-transformation and continuous occurrence of Fenton reaction. In vitro and in vivo evaluations verify that through the positive feedback loop, Ce6-CD/ Fc-pep-PEG can induce a potent antitumor immune response and achieve ROS-potentiated elimination of primary tumor and bone metastasis. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is the most prevalent inflammatory joint disease worldwide, leading to irreversible disability and even mortality. Unfortunately, current treatment regimens fail to cure RA due to low therapeutic responses and off-target side effects. Herein, a neutrophil membrane-cloaked, natural anti-arthritic agent leonurine (Leo), and catalase (CAT) co-loaded nanoliposomal system (Leo@CAT@NM-Lipo) is constructed to remodel the hostile microenvironment for RA remission. Due to the inflammation tropism inherited from neutrophils, Leo@CAT@NM-Lipo can target and accumulate in the inflamed joint cavity where high-level ROS can be catalyzed into oxygen by CAT to simultaneously accelerate the drug release and alleviate hypoxia at the lesion site. Besides, the neutrophil membrane camouflaging also enhances the anti-inflammatory potentials of Leo@CAT@NM-Lipo by robustly absorbing pro-arthritogenic cytokines and chemokines. Consequently, Leo@CAT@NM-Lipo successfully alleviated paw swelling, reduced arthritis score, mitigated bone and cartilage damage, and reversed multiple organ dysfunctions in adjuvant-induced arthritis rats (AIA) rats by synergistic effects of macrophage polarization, inflammation resolution, ROS scavenging, and hypoxia relief. Furthermore, Leo@CAT@NM-Lipo manifested excellent biocompatibility both at the cellular and animal levels. Taken together, the study provided a neutrophil-mimetic and ROS responsive nanoplatform for targeted RA therapy and represented a promising paradigm for the treatment of a variety of inflammation-dominated diseases., (© 2023 Wiley‐VCH GmbH.)

Tanshinone IIA (TS-IIA) and salvianic acid A (SAA) are the main pharmacological active constituents of Danshen, which exhibit potent effects on atherosclerosis. A combination of TS-IIA and SAA might exert a synergistic antiatherosclerotic effect. However, the opposite solubility profiles of TS-IIA and SAA might lead to difficulty in achieving a synergistic combined effect of the two active components. Therefore, in this work, we fabricated a ROS-responsive prodrug micelle for the codelivery of TS-IIA and SAA (TS-IIA-PM) by self-assembling amphiphilic block copolymer PEG 5000 -SAA/PLA 10000 -APBA. The amphiphilic polymer was characterized by 1 H NMR, FTIR, and alizarin red S competition tests. The ROS responsiveness of TS-IIA-PM was evidenced by time-course monitoring of particle size and morphology changes and drug release behavior in the presence of 1 mM H 2 O 2 . We found TS-IIA-PM was stable according to its critical micelle concentration and the unchanged particle sizes in 10% FBS for 7 days. The results of in vitro and in vivo tests revealed that TS-IIA-PM was safe and biocompatible. Furthermore, it was observed that TS-IIA and prodrug micelle could produce synergistic antiatherosclerotic effect based on the results of the antioxidant study, which was further confirmed by a series of pharmocodynamics studies, such as in vitro DiI-oxLDL uptake study, oil red O staining, cholesterol efflux study, inflammatory cytokine analysis, in vivo CD68 immunostaining, and lipid disposition staining studies. Collectively, TS-IIA-PM holds great potential for the safe and efficient codelivery of TS-IIA and SAA for synergistic antiatherosclerosis.

Chitosan (CS) is a biodegradable, biocompatible cationic polysaccharide based natural polymer with antibacterial and anti-inflammatory properties. Hydrogels made from CS have found their applications in wound healing, tissue regeneration and drug delivery. Although, mucoadhesive properties are resulted from the polycationic nature of CS, in hydrogel form amines are engaged in interactions with water leading to decrease in mucoadhesive properties. In case of injury, presence of elevated level of reactive oxygen species (ROS) has inspired many drug delivery platforms to conjugate ROS responsive linkers for on demand drug delivery. In this report we have conjugated a reactive oxygen species (ROS) responsive thioketal (Tk) linker and nucleobase thymine (Thy) with CS. Cryogel from this doubly functionalized polymer CS-Thy-Tk was prepared through crosslinking with sodium alginate. Inosine was loaded on the scaffold and studied for its release under oxidative condition. We anticipated that the presence of thymine shall retain the mucoadhesive nature of the CS-Thy-Tk polymer in hydrogel form and when placed at the site of injury, due to the presence of excessive ROS at inflammatory condition, loaded drug shall release due to degradation of the linker. Porous cryogel scaffold was prepared via chemical crosslinking of amine functional group of chitosan with carboxylic acid containing polysaccharide sodium alginate. The cryogel was evaluated for porosity (FE-SEM), rheology, swelling, degradation, mucoadhesive properties and biocompatibility. Resulted scaffold was found to be porous with average pore size of 107 ± 23 μm, biocompatible, hemocompatible and possesses improved mucoadhesive property (mucin binding efficiency of 19.54 %) which was found to be 4 times better as compared to chitosan (4.53 %). The cumulative drug release found to be better in the presence of H 2 O 2 (∼90 %) when compared to that of PBS alone (∼60–70 %). Therefore, the modified CS-Thy-TK polymer may hold potential as interesting scaffold in case of conditions associated with elevated ROS level such as injury and tumor. [Display omitted] • Double functionalized chitosan • Porous cryogel for drug release and wound healing • Biocompatible and hemo-compatible • ROS responsive and on demand drug release [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic or relapsing inflammatory disease with limited therapeutic outcomes. Pterostilbene (PSB) is a polyphenol-based anti-oxidant that has received extensive interest for its intrinsic anti-inflammatory and anti-oxidative activities. This work aims to develop a reactive oxygen species (ROS)-responsive, folic acid (FA)-functionalized nanoparticle (NP) for efficient PSB delivery to treat UC. The resulting PSB@NP-FA had a nano-scaled diameter of 231 nm and a spherical shape. With ROS-responsive release and ROS-scavenging properties, PSB@NP could effectively scavenge H 2 O 2 , thereby protecting cells from H 2 O 2 -induced oxidative damage. After FA modification, the resulting PSB@NP-FA could be internalized by RAW 264.7 and Colon-26 cells efficiently and preferentially localized to the inflamed colon. In dextran sulfate sodium (DSS)-induced colitis models, PSB@NP-FA showed a prominent ROS-scavenging capacity and anti-inflammatory activity, therefore relieving murine colitis effectively. Mechanism results suggested that PSB@NP-FA ameliorated colitis by regulating dendritic cells (DCs), promoting macrophage polarization, and regulating T cell infiltration. Both innate and adaptive immunity were involved. More importantly, the combination of the PSB and dexamethasone (DEX) enhanced the therapeutic efficacy of colitis. This ROS-responsive and ROS-scavenging nanocarrier represents an alternative therapeutic approach to UC. It can also be used as an enhancer for classic anti-inflammatory drugs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Atherosclerosis, which is triggered by endothelial damage, progressive local inflammation and excessive lipid accumulation, is one of the most common cardiovascular diseases in recent years. Drug delivery systems have shown great potential for the accurate diagnosis and effective treatment of early atherosclerosis, but are accompanied by disadvantages such as poor stability, lack of active targeting and non-specific recognition capabilities, which still need to be further developed. In our work, a multifunctional nanoparticle (LFP/PCDPD) with reactive oxygen species (ROS) responsive drug release, lipid removal, and lipid-specific AIE fluorescence imaging was constructed. Cyclodextrin structure with lipid removal function and PMEMA blocks with ROS-response-mediated hydrophobic to hydrophilic conversion were simultaneously introduced into the structure of LFP/PCDPD to load the anti-inflammatory drug prednisolone (Pred) and lipid-specific AIEgen (LFP). The active targeting function of LFP/PCDPD was conferred by the high affinity of dextran to the vascular adhesion molecule-1 (VCAM-1) and CD44 receptor on the surface of broken endothelial cells. After intravenous injection into ApoE−/− mice, LFP/PCDPD actively enriched in the microenvironment of local ROS overexpression and rich lipids in atherosclerosis. Pred and LFP were released while lipids were removed, thus enabling proactive targeting of atherosclerosis and efficient "two-pronged" treatment. [ABSTRACT FROM AUTHOR]

• ROS-responsive prodrug was constructed for controllable drug release in AS. • VLA-4 overexpressed cell membrane enhanced target delivery to inflammation. • Biomimetic and smart nanomedicine was improved for safe and efficient AS management. The development of atherosclerosis (AS) is closely related to inflammation. The common feature of inflammatory sites is upregulation of vascular cell adhesion molecule-1 (VCAM-1), which has a strong affinity with very late antigen-4 (VLA-4). Endothelial cell membranes overexpressing VLA-4 (OEM) were used to camouflage rapamycin nanoparticles (RAP NPs) with reactive oxygen species (ROS) responsiveness to construct biomimetic nanodrugs OEM@RAP NPs. These nanoparticles were capable of enhancing the active target drug delivery and ROS-responsive drug release under the pathological overexpression of VCAM-1 and accumulation of ROS stimulus. In vitro and in vivo investigations confirmed that OEM@RAP NPs could enhance the active target drug delivery to atherosclerotic plaques and increase drug accumulation in the focal site, thus improving the bioavailability of drugs, reducing side effects and inhibiting the occurrence and development of atherosclerosis. [ABSTRACT FROM AUTHOR]

Oxidative stress is a key factor in the development of inflammatory diseases. Elimination of reactive oxygen species (ROS) in the inflamed colon has been confirmed as an effective strategy to alleviate inflammatory bowel disease (IBD). The conventional approaches will cause systemic absorption and potential side effects. To address these issues, we develop a nanomedicine (LS@PDA NPs) that is capable of delivering to target inflammatory lesions by electrostatic adsorption, subsequently effectively scavenging the excess ROS and alleviating inflammation to ameliorate ulcerative colitis (UC). In the DSS induced acute colitis mice model, LS@PDA NPs can significantly reduce the production of pro-inflammatory cytokines, alleviate oxidative stress, and promote the favorable recovery of the damaged colonic tissue. These results indicate that LS@PDA NPs are able to effectively alleviate intestinal inflammation and provide strong theoretical support for the treatment of other inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Combining chemotherapy with photothermal therapy (PTT) for cancer treatment could overcome the inherent limitations of both single-modality chemotherapy and PTT. However, the obstacle of accurate drug delivery to tumor sites based on chemo-photothermal remains challenging. This article describes development of a reactive oxygen species (ROS)-responsive hyaluronic acid-based nanoparticle to overcome these drawbacks. Herein, HA-TK-MTX (HTM) was synthesized by a ROS-responsive cleaved thioketal moiety linker (TK) of methotrexate (MTX) and hyaluronic acid (HA). Through hydrophobic interaction and π-π stacking interaction, a photothermal agent IR780 was integrated into the HTM, and the IR780/HTM nanoparticles (IHTM NPs) were obtained. The IHTM NPs show high photostability, excellent photothermal performance, remarkable tumor-targeting ability, and ROS sensibility. Due to the accurate drug delivery ability and superior chemo-photothermal treatment effect of IHTM NPs, the tumor inhibition rate reached 70.95% for 4T1 tumor-bearing mice. This work serves as a precedent for the chemo-photothermal therapy of cancer by rationally designing ROS-responsive nanoparticles.

The integration of hypoxia-activated chemotherapy with photodynamic therapy (PDT) has newly become a potent strategy for tumor treatment. Herein, a reactive oxygen species (ROS)-responsive drug carriers (PS@AQ4N/mPEG-b-PSe NPs) are fabricated based on the amphiphilic selenium-containing methoxy poly(ethylene glycol)-polycarbonate (mPEG-b-PSe), the hydrophobic photosensitizer (PS), and hypoxia-activated prodrug Banoxantrone (AQ4N). The obtained nanoparticles are spherical with an average diameter of 100 nm as characterized by transmission electron microscope (TEM) and dynamic laser scattering (DLS) respectively. The encapsulation efficiency of the PS and AQ4N reaches 92.83% and 51.04% at different conditions, respectively, by UV-vis spectrophotometer. It is found that the drug release is accelerated due to the good ROS responsiveness of mPEG-b-PSe and the cumulative release of AQ4N is up to 89% within 30 h. The cell test demonstrates that the nanoparticles dissociate when triggered by the ROS stimuli in the cancer cells, thus the PS is exposed to more oxygen and the ROS generation efficiency is enhanced accordingly. The consumption of oxygen during PDT leads to the increased tumor hypoxia, and subsequently activates AQ4N into cytotoxic counterpart to inhibit tumor growth. Therefore, the synergistic therapeutic efficacy demonstrates this drug delivery has great potential for antitumor therapy., (© 2021 Wiley-VCH GmbH.)