Peroxide Nanoparticles Research Articles

Bimetallic peroxide nanoparticles induce PANoptosis by disrupting ion homeostasis for enhanced immunotherapy

Bimetallic peroxide nanoparticles induce PANoptosis by disrupting ion homeostasis for enhanced immunotherapy

Engineering Robust Silver-Decorated calcium peroxide Nano-Antibacterial Platforms for chemodynamic enhanced sterilization

Calcium peroxide (CaO2) is commonly used as a hydrogen peroxide (H2O2) donor to eliminate bacterial infections. However, the rapid dissociation of CaO2 and the explosive release of H2O2 have limited the development of CaO2 in the antibacterial field. Therefore, a series of silver nanoparticles (AgNPs) functionalized bacteria-triggered smart hydrogels (CSA-H) that integrate sustained release of nanoparticles and localized chemodynamic sterilization were constructed. The pH-responsive hydrogel formed through the Schiff base reaction enables the responsive release of CaO2 nanoparticles while simultaneously regulating the concentration of H2O2 within the bacterial infection microenvironment. AgNPs are capable of reacting with H2O2 under mildly acidic conditions to produce hydroxyl radicals with enhanced antimicrobial activity. The antimicrobial results demonstrated that AgNPs functionalized silicon dioxide-coated calcium peroxide (CaO2@SiO2/AgNPs) nanoparticles exhibited enhanced bactericidal activity compared to AgNPs or CaO2 alone. Furthermore, CSA-H hydrogels exhibited significant antibacterial activity against S. aureus and E. coli under the dual effect of AgNPs and pH-driven Fenton-like reactions. This chemodynamic antibacterial platform is environmentally responsive and provides a promising strategy for creating multifunctional hydrogels loaded with nano-enzymes, thus advancing the development of AgNPs in chemodynamic-antibacterial related applications.

Bimetallic peroxide-based nanotherapeutics for immunometabolic intervention and induction of immunogenic cell death to augment cancer immunotherapy

Immunotherapy has transformed cancer treatment, but its efficacy is often limited by the immunosuppressive characteristics of the tumor microenvironment (TME), which are predominantly influenced by the metabolism of cancer cells. Among these metabolic pathways, the indoleamine 2,3-dioxygenase (IDO) pathway is particularly crucial, as it significantly contributes to TME suppression and influences immune cell activity. Additionally, inducing immunogenic cell death (ICD) in tumor cells can reverse the immunosuppressive TME, thereby enhancing the efficacy of immunotherapy. Herein, we develop CGDMRR, a novel bimetallic peroxide-based nanodrug based on copper-cerium peroxide nanoparticles. These nanotherapeutics are engineered to mitigate tumor hypoxia and deliver therapeutics such as 1-methyltryptophan (1MT), glucose oxidase (GOx), and doxorubicin (Dox) in a targeted manner. The design aims to alleviate tumor hypoxia, reduce the immunosuppressive effects of the IDO pathway, and promote ICD. CGDMRR effectively inhibits the growth of 4T1 tumors and elicits antitumor immune responses by leveraging immunometabolic interventions and therapies that induce ICD. Furthermore, when CGDMRR is combined with a clinically certified anti-PD-L1 antibody, its efficacy in inhibiting tumor growth is enhanced. This improved efficacy extends beyond unilateral tumor models, also affecting bilateral tumors and lung metastases, due to the activation of systemic antitumor immunity. This study underscores CGDMRR's potential to augment the efficacy of PD-L1 blockade in breast cancer immunotherapy.

Metal Peroxide Nanoparticles for Modulating the Tumor Microenvironment: Current Status and Recent Prospects

Metal Peroxide Nanoparticles for Modulating the Tumor Microenvironment: Current Status and Recent Prospects

Antimicrobial and antibiotic-potentiating effect of calcium peroxide nanoparticles on oral bacterial biofilms

Bacterial biofilms represent a prominent biological barrier against physical and chemical attacks. Disturbing the anaerobic microenvironment within biofilms by co-delivery of oxygen appears as a promising strategy to enhance the activity of an antibiotic. Here, we report the effect of oxygen-producing calcium peroxide nanoparticles (CaO2 NP) in combination with tobramycin sulfate (Tob). On Pseudomonas aeruginosa PAO1 biofilms in vitro, the additive effect of CaO2 NP towards Tob activity enhanced biofilm eradication by 2 log compared to Tob alone. For natural biofilms grown in the oral cavity of human volunteers in situ, treatment by CaO2 NP alone slightly increased the fraction of dead bacteria from 44% in various controls, including Tob alone, to 57%. However, the combination of CaO2 NP with Tob further increased the fraction of dead bacteria to 69%. These data confirm the intrinsic antimicrobial and antibiotic-potentiating effect of CaO2 NP also in a clinically relevant setting.

A Robust ROS Generation and Ferroptotic Lipid Modulation Nanosystem for Mutual Reinforcement of Ferroptosis and Cancer Immunotherapy.

Ferroptosis initiation is often utilized for synergistic immunotherapy. While, current immunotherapy is limited by an immunosuppressive tumor microenvironment (TME), and ferroptosis is limited by insufficient reactive oxygen species (ROS) and ferroptotic lipids in tumor cells. Here, an arachidonic acid (AA) loaded nanosystem (CTFAP) is developed to mutually reinforce ferroptosis and cancer immunotherapy by augmenting ROS generation and modulating ferroptotic lipids. CTFAP is composed of acid-responsive core calcium peroxide (CaO2) nanoparticles, ferroptotic lipids sponsor AA, tetracarboxylic porphyrin (TCPP) and Fe3+ based metal-organic framework structure, and biocompatible mPEG-DSPE for improved stability. Once endocytosed by tumor cells, CTFAP can release oxygen (O2) and hydrogen peroxide (H2O2) in the acidic TME, facilitating TCPP-based sonodynamic therapy and Fe3+-mediated Fenton-like reactions to generate substantial ROS for cell ferroptosis initiation. The immunogenic cell death (ICD) after ferroptosis promotes interferon γ (IFN-γ) secretion to up-regulate the expression of long-chain family member 4 (ACSL4), cooperating with the released AA from CTFAP to accelerate the accumulation of lipid peroxidation (LPO) and thereby promoting ferroptosis in cancer cells.CTFAP with ultrasound treatment efficiently suppresses tumor growth, has great potential to challenges in cancer immunotherapy.

Calcium Peroxide-Based Hydrogels Enable Biphasic Release of Hydrogen Peroxide for Infected Wound Healing.

Wound infection is a major factor affecting the speed and quality of wound healing. While hydrogen peroxide (H2O2) is recognized for its antibacterial capacity and facilitation of wound healing, its administration requires careful dosage differentiation. Inappropriately matched dosages can protract the healing of infected wounds. Herein, a calcium peroxide-based hydrogel (CPO-Alg hydrogel) is fabricated to enable a biphasic tapered release of H2O2, ensuring robust initial antimicrobial activity followed by sustained promotion of cellular proliferation of wound healing. The design of the hydrogel allowed for the calcium peroxide nanoparticles (CPO NPs) being in two spatial niches within the gel framework. When applied to infectious wounds, CPO NPs with weak constraints are promptly released out of the gel, penetrating into infected regions to serve as antibacterial agents that eliminate bacteria and biofilms at high concentrations. Conversely, the entrapped CPO NPs structurally integrated into the gel remain confined, thus gradually degrading and allowing a mild release of H2O2 through hydrolysis in a moist environment that contributes to the cell growth in the later stage. The CPO-Alg hydrogel represents an innovative and practical solution for the antimicrobial protection of chronic wounds, offering promising prospects for advancing wound healing.

Glucose Oxidase-Coated Calcium Peroxide Nanoparticles as an Innovative Catalyst for In Situ H2O2-Releasing Hydrogels.

In situ forming and hydrogen peroxide (H2O2)-releasing hydrogels have been considered as attractive matrices for various biomedical applications. Particularly, horseradish peroxidase (HRP)-catalyzed crosslinking reaction serves efficient method to create in situ forming hydrogels due to its advantageous features, such as mild reaction conditions, rapid gelation rate, tunable mechanical strength, and excellent biocompatibility. Herein, a novel HRP-crosslinked hydrogel system is reported that can produce H2O2 in situ for long-term applications, using glucose oxidase-coated calcium peroxide nanoparticles (CaO2@GOx NPs). In this system, CaO2 gradually produced H2O2 to support the HRP-mediated hydrogelation, while GOx further catalyzed the oxidation of glucose for in situ H2O2 generation. As the hydrogel is formed rapidly is expected and the H2O2 release behavior is prolonged up to 10 days. Interestingly, hydrogels formed by HRP/CaO2@GOx-mediated crosslinking reaction provided a favorable 3D microenvironment to support the viability and proliferation of fibroblasts, compared to that of hydrogels formed by either HRP/H2O2 or HRP/CaO2/GOx-mediated crosslinking reaction. Furthermore, HRP/CaO2@GOx-crosslinked hydrogel enhanced the angiogenic activities of endothelial cells, which is demonstrated by the in vitro tube formation test and in ovo chicken chorioallantoic membrane model. Therefore, HRP/CaO2@GOx-catalyzed hydrogels is suggested as potential in situ H2O2-releasing materials for a wide range of biomedical applications.

Design of a two functional permeable reactive barrier for synergistic enzymatic and microbial bioremediation of phenol-contaminated waters: laboratory column evaluation

The present study aimed to develop a system using a combination of enzymatic and microbial degradation techniques for removing phenol from contaminated water. In our prior research, the HRP enzyme extracted from horseradish roots was utilized within a core-shell microcapsule to reduce phenolic shock, serving as a monolayer column. To complete the phenol removal process, a second column containing degrading microorganisms was added to the last column in this research. Phenol-degrading bacteria were isolated from different microbial sources on a phenolic base medium. Additionally, encapsulated calcium peroxide nanoparticles were used to provide dissolved oxygen for the microbial population. Results showed that the both isolated strains, WC1 and CC1, were able to completely remove phenol from the contaminated influent water the range within 5 to 7 days, respectively. Molecular identification showed 99.8% similarity for WC1 isolate to Stenotrophomonas rizophila strain e-p10 and 99.9% similarity for CC1 isolate to Bacillus cereus strain IAM 12,605. The results also indicated that columns using activated sludge as a microbial source had the highest removal rate, with the microbial biofilm completely removing 100% of the 100 mg/L phenol concentration in contaminated influent water after 40 days. Finally, the concurrent use of core-shell microcapsules containing enzymes and capsules containing Stenotrophomonas sp. WC1 strain in two continuous column reactors was able to completely remove phenol from polluted water with a concentration of 500 mg/L for a period of 20 days. The results suggest that a combination of enzymatic and microbial degrading systems can be used as a new system to remove phenol from polluted streams with higher concentrations of phenol by eliminating the shock of phenol on the microbial population.

Hollow mesoporous calcium peroxide nanoparticles for drug-free tumor calcicoptosis therapy

Calcium ions (Ca2+) participate in the regulation of cellular apoptosis as a second messenger. Calcium overload, which refers to the abnormal elevation of intracellular Ca2+ concentration, is a factor that can lead to cell death. Here, based on the unique biological effects of Ca2+, hollow mesoporous calcium peroxide nanoparticles (HMCPN) were developed by a facile hydrolysis-precipitation method for drug-free tumor calcicoptosis therapy. The average pore size of the optimized HMCPN17 is 6.4 nm, and the surface area is 81.3 m2/g, which enables HMCPN17 with high drug loading capability. The Ca2+ release from HMCPN17 is much faster at pH 6.8 than that at pH 7.4, which can be ascribed to the acid-triggered conversion of HMCPN17 to Ca2+ and H2O2, indicating a pH-responsive decomposition behavior of HMCPN17. The high drug loading contents of doxorubicin (DOX) and/or sorafenib (SFN) indicate that HMCPN17 can be employed as a generic drug delivery system (DDS). The in vitro and in vivo results reinforce the high calcicoptosis therapeutic efficacy of tumors by our HMCPN17 without drug loading, which can be attributed to the efficient accumulation in tumors and the ability of H2O2 and Ca2+ production at acidic TME. Our HMCPN17 has broad application prospect for construction of multi-drug-loaded composite nanomaterials with diversified functions for the treatment of tumors. Statement of significanceThe combination of hollow mesoporous nanomaterials and calcium peroxide nanoparticles has a wide range of applications in the synergistic treatment of tumors. In this study, hollow mesoporous calcium peroxide nanoparticles (HMCPN) were developed based on a simple hydrolysis-precipitation method for tumor calcicoptosis therapy without drug loading. The high drug loading contents of DOX and/or SFN indicate that our HMCPN can serve as a generic DDS. The experimental results demonstrated the high calcicoptosis therapeutic efficacy of HMCPN on tumors even without drug loading.

Microneedle Patch Loaded with Calcium Peroxide Nanoparticles for Oxygen Healing and Biofilm Inhibition in Diabetic Wound Healing

Microneedle Patch Loaded with Calcium Peroxide Nanoparticles for Oxygen Healing and Biofilm Inhibition in Diabetic Wound Healing

Dendrimer/metal-phenolic nanocomplexes encapsulating CuO2 for targeted magnetic resonance imaging and enhanced ferroptosis/cuproptosis/chemodynamic therapy by regulating the tumor microenvironment

The combination of ferroptosis, cuproptosis, and chemodynamic therapy (CDT) would be a potential strategy for tumor diagnosis and enhanced treatment. However, the therapeutic effect was severely limited by the lack of specific delivery of catalytic ions and the low Fenton reaction efficiency in tumor microenvironment (TME) with excess glutathione, limited acidity and insufficient endogenous hydrogen peroxide. In this work, p-carboxybenzenesulfonamide (BS), a carbonic anhydrase IX (CA IX) inhibitor, was modified on the surface of generation-5 poly(amidoamine) dendrimer to load copper peroxide nanoparticles, which were complexed with iron (Fe)-tannic acid (TF) networks for targeted magnetic resonance (MR) imaging and enhanced ferroptosis/cuproptosis/CDT by regulating TME. The formed CuO2@G5-BS/TF nanocomplexes with an average size of 39.4 nm could be specifically accumulated at tumor site and effectively internalized by metastatic 4T1 cells via the specific interaction between BS and CA IX over-expressed on tumor cells. Meanwhile, the inhibition of CA IX activity could not only decrease the intracellular pH to accelerate Fe3+/Cu2+ release, H2O2 self-supply and Fenton reaction, but also suppress tumor metastasis by alleviating the extracellular acidity in TME. Moreover, the reduction of Fe3+/Cu2+ by intracellular glutathione (GSH) could further amplify ROS generation and enhance CDT efficacy, and the GSH depletion could in turn inhibit GPX-4 mediated antioxidant reaction to induce ferroptosis, resulting in effective therapeutic efficacy. In vivo experimental results demonstrated that CuO2@G5-BS/TF could provide better tumor MR imaging, effectively inhibit the growth and metastasis of 4T1 breast tumors, and be metabolized without significant systemic toxicity. Thus, CuO2@G5-BS/TF nanocomplexes provided a new approach for targeted MR imaging and enhanced ferroptosis/cuproptosis/CDT of triple-negative breast cancer. Statement of significanceTaking the advantage of dendrimer and metal-phenolic system, stable CuO2@G5-BS/TF nanocomplexes with an average size of 39.4 nm were synthesized to efficiently load Fe3+ and CuO2 nanoparticles for TNBC treatment and MR imaging. CuO2@G5-BS/TF nanocomplexes could target tumor cells overexpressing CAIX via the specific binding with BS, and the inhibition of CAIX activity could not only decrease the intracellular pH to accelerate Fe3+/Cu2+ release, H2O2 self-supply and Fenton reaction, but also suppress tumor metastasis by alleviating the extracellular acidity. The reduction of Fe3+/Cu2+ by intracellular GSH could further amplify ·OH generation, and the GSH depletion could in turn inhibit GPX-4 mediated antioxidant reaction to induce ferroptosis, resulting in effective therapeutic efficacy by enhanced ferroptosis/cuproptosis/CDT via tumor microenvironment regulation.

Infection-Free and Enhanced Wound Healing Potential of Alginate Gels Incorporating Silver and Tannylated Calcium Peroxide Nanoparticles.

The treatment of chronic wounds involves precise requirements and complex challenges, as the healing process cannot go beyond the inflammatory phase, therefore increasing the healing time and implying a higher risk of opportunistic infection. Following a better understanding of the healing process, oxygen supply has been validated as a therapeutic approach to improve and speed up wound healing. Moreover, the local implications of antimicrobial agents (such as silver-based nano-compounds) significantly support the normal healing process, by combating bacterial contamination and colonization. In this study, silver (S) and tannylated calcium peroxide (CaO2@TA) nanoparticles were obtained by adapted microfluidic and precipitation synthesis methods, respectively. After complementary physicochemical evaluation, both types of nanoparticles were loaded in (Alg) alginate-based gels that were further evaluated as possible dressings for wound healing. The obtained composites showed a porous structure and uniform distribution of nanoparticles through the polymeric matrix (evidenced by spectrophotometric analysis and electron microscopy studies), together with a good swelling capacity. The as-proposed gel dressings exhibited a constant and suitable concentration of released oxygen, as shown for up to eight hours (UV-Vis investigation). The biofilm modulation data indicated a synergistic antimicrobial effect between silver and tannylated calcium peroxide nanoparticles, with a prominent inhibitory action against the Gram-positive bacterial biofilm after 48 h. Beneficial effects in the human keratinocytes cultured in contact with the obtained materials were demonstrated by the performed tests, such as MTT, LDH, and NO.

Enhanced phenanthrene biodegradation in river sediments by harnessing calcium peroxide nanoparticles and minerals in Sphingomonas sp. DSM 7526 cultivation

ABSTRACT Coupling chemical oxidation and biodegradation to remediate polycyclic aromatic hydrocarbon (PAH)-contaminated sediment has recently gained significant attention. In this study, calcium peroxide nanoparticles (nCaO2) were utilized as an innovative oxygen-releasing compound for in-situ chemical oxidation. The study investigates the bioremediation of phenanthrene (PHE)-contaminated sediment inoculated with Sphingomonas sp. DSM 7526 bacteria and treated with either aeration or nCaO2. Using three different culture media, the biodegradation efficiencies of PHE-contaminated anoxic sediment, aerobic sediment, and sediment treated with 0.2% w/w nCaO2 ranged from 57.45% to 63.52%, 69.87% to 71.00%, and 92.80% to 94.67%, respectively. These values were significantly higher compared to those observed in non-inoculated sediments. Additionally, the type of culture medium had a prominent effect on the amount of PHE removal. The presence of minerals in the culture medium increased the percentage of PHE removal compared to distilled water by about 2–10%. On the other hand, although the application of CaO2 nanoparticles negatively impacted the abundance of sediment bacteria, resulting in a 30–42% decrease in colony-forming units after 30 days of treatment, the highest PHE removal was obtained when coupling biodegradation and chemical oxidation. These findings demonstrate the successful application of bioaugmentation and chemical oxidation processes for treating PAH-contaminated sediment.

Remodeling Microenvironment for Implant-Associated Osteomyelitis by Dual Metal Peroxide.

Implant-associated osteomyelitis (IAOM) is characterized by bone infection and destruction; current therapy of antibiotic treatment and surgical debridement often results in drug resistance and bone defect. It is challenging to develop an antibiotic-free bactericidal and osteogenic-enhanced strategy for IAOM. Herein, an IAOM-tailored antibacterial and osteoinductive composite of copper (Cu)-strontium (Sr) peroxide nanoparticles (CSp NPs), encapsulated in polyethylene glycol diacrylate (PEGDA) (CSp@PEGDA), is designed. The dual functional CSp NPs display hydrogen peroxide (H2O2) self-supplying and Fenton catalytic Cu2+ ions' release, generating plenty of hydroxyl radical (•OH) in a pH-responsive manner for bacterial killing, while the released Sr2+ promotes the in vitro osteogenicity regarding cell proliferation, alkaline phosphatase activity, extracellular matrix calcification, and osteo-associated genes expression. The integration of Cu2+ and Sr2+ in CSp NPs together with the coated PEGDA hydrogel ensures the stable and sustainable ion release during short- and long-term periods. Benefitted from the injectablity and photo-crosslink ability, CSp@PEGDA is able to thoroughly fill the infectious site and gelate in situ for bacterial elimination and bone regeneration, which is verified through in vivo evaluation using a clinical-simulating IAOM mouse model. These favorable abilities of CSp@PEGDA precisely meet the multiple therapeutic needs and pave a promising way for implant-associated osteomyelitis treatment.

Nanoengineered oxygen-releasing polymeric scaffold with sustained release of dexamethasone for bone regeneration

Maintaining the continuous oxygen supply and proper cell growth before blood vessel ingrowth at the bone defect site are considerably significant issues in bone regeneration. Oxygen-producing scaffolds can supply oxygen and avoid hypoxia leading to expedited bone regeneration. Herein, first oxygen-producing calcium peroxide nanoparticles (CPO NPs) are synthesized, and subsequently, the various amounts of synthesized CPO NPs (0.1, 0.5, and 1 wt/v%) loaded in the scaffold composite, which is developed by simple physical blending of chitosan (CS) and polycaprolactone (PCL) polymers. To deliver the synergistic therapeutic effect, dexamethasone (DEX), known for its potential anti-inflammatory and osteogenic properties, is loaded into the nanocomposite scaffolds. The extensive physicochemical characterizations of nanocomposite scaffolds confirm the successful loading of CPO NPs, adequate porous morphology, pore size, hydrophilicity, and biodegradability. In vitro, biological studies support the antibacterial, hemocompatible, and cytocompatible (MG-63 and MC3T3-E1 cells) nature of the material when tested on respective cells. Field emission scanning electron microscopy and energy-dispersive x-ray spectroscopy confirm the successful biomineralization of the scaffolds. Scaffolds also exhibit the sustained release of DEX and efficient protein adsorption. This study revealed that a nanoengineered scaffold loaded with CPO NPs (PCL/CS/DEX/CPO 3) is a suitable candidate for bone tissue regeneration.

Improved photocatalytic disinfection performance of graphitic carbon nitride through hybridization with humic acid /zinc peroxide: A synergistic generation of antimicrobial reactive oxygen species

Photocatalytic disinfection of bacteria using photosensitive nanomaterials is an efficient method for bacteria inactivation and is considered a beneficial alternative to chemical disinfectants that produce harmful by-products. However, due to the limited application scope of photocatalysts, the antibacterial efficiency remains unsatisfactory. To enhance the photocatalytic efficiency of the non-metal photosensitizer, graphitic carbon nitride (g-C3N4) nanosheets, they were composited with a metal-based photosensitizer, zinc peroxide (ZnO2) nanoparticles, with the aim of humic acid (HA). Besides the self-generating ability of H2O2 by ZnO2 in an aqueous medium, its deposition over g-C3N4 nanosheets enhances visible light harvesting and increases both surface area and active sites, thereby enhancing photocatalytic efficiency. The resulting composite, g-C3N4/ZnO2, produced more H2O2, •OH, and O2•- radicals than either component when exposed to visible light. Moreover, the photocatalyst demonstrated enhanced photocatalytic disinfection efficacy against Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) under dark conditions compared to pure g-C3N4 nanosheets. However, a notably greater antibacterial activity was observed when the nanocomposites were subjected to light irradiation. FESEM images and live-dead assays revealed the physical contact of the nanocomposite with the surface of bacterial cells and the loss of cell membrane integrity. Furthermore, it was observed that there was greater cellular uptake of nanocomposites into cells and the generation of reactive oxygen species (ROS) under light irradiation compared to similar conditions in the dark, leading to an increased photoinactivation rate of bacteria. The enhanced photocatalytic and antibacterial activities of g-C3N4/ZnO2 nanocomposites make them attractive for a range of applications, including use in nanomedicine and environmental surface disinfection.

Fenton-like Reaction Inspired "·OH Catalyzed" Osteogenic Process for the Treatment of Osteoporosis.

Inspired by the Fenton-like reaction, this work combines copper peroxide (CP) nanoparticles with black phosphorus (BP) nanosheets to form a hydroxyl radical (·OH)-centered "catalytic" osteogenic system. CP-produced ·OH interacts with BP to rapidly produce a large amount of phosphate ions, thus accelerating self-mineralization and promoting bone formation. In turn, BP not only exerts anti-inflammatory effects, thereby providing a favorable microenvironment for bone formation, but also offsets the potential toxicity of CP induced by reactive oxygen species (ROS). Together with copper ions (Cu2+), phosphate ions are also released as a byproduct of this process, which can contribute to the comprehensive promotion of osteogenesis.

Zinc Oxide and Peroxide Nanoparticles – from Chemical Synthesis to Electrochemical Analysis and Wastewater Filtration

Zinc Oxide and Peroxide Nanoparticles – from Chemical Synthesis to Electrochemical Analysis and Wastewater Filtration

Self-Disassembling and Oxygen-Generating Porphyrin-Lipoprotein Nanoparticle for Targeted Glioblastoma Resection and Enhanced Photodynamic Therapy.

The dismal prognosis for glioblastoma multiform (GBM) patients is primarily attributed to the highly invasive tumor residual that remained after surgical intervention. The development of precise intraoperative imaging and postoperative residual removal techniques will facilitate the gross total elimination of GBM. Here, a self-disassembling porphyrin lipoprotein-coated calcium peroxide nanoparticles (PLCNP) is developed to target GBM via macropinocytosis, allowing for fluorescence-guided surgery of GBM and improving photodynamic treatment (PDT) of GBM residual by alleviating hypoxia. By reducing self-quenching and enhancing lysosome escape efficiency, the incorporation of calcium peroxide (CaO2) cores in PLCNP amplifies the fluorescence intensity of porphyrin-lipid. Furthermore, the CaO2 core has diminished tumor hypoxia and improves the PDT efficacy of PLCNP, enabling low-dose PDT and reversing tumor progression induced by hypoxia aggravation following PDT. Taken together, this self-disassembling and oxygen-generating porphyrin-lipoprotein nanoparticle may serve as a promising all-in-one nanotheranostic platform for guiding precise GBM excision and empowering post-operative PDT, providing a clinically applicable strategy to combat GBM in a safe and effective manner.