Inorganic Nanozyme with Combined Self-Oxygenation/Degradable Capabilities for Sensitized Cancer Immunochemotherapy

Recently emerged cancer immunochemotherapy has provided enormous new possibilities to replace traditional chemotherapy in fighting tumor.However,the treatment efficacy is hampered by tumor hypoxiainduced immunosuppression in tumor microenvironment(TME).Herein,we fabricated a self-oxygenation/degradable inorganic nanozyme with a core-shell structure to relieve tumor hypoxia in cancer immunochemotherapy.By integrating the biocompatible CaO2 as the oxygen-storing component,this strategy is more effective than the earlier designed nanocarriers for delivering oxygen or H2O2,and thus provides remarkable oxygenation and long-term capability in relieving hypoxia throughout the tumor tissue.Consequently,in vivo tests validate that the delivery system can successfully relieve hypoxia and reverse the immunosuppressive TME to favor antitumor immune responses,leading to enhanced chemoimmunotherapy with cytotoxic T lymphocyte-associated antigen 4 blockade.Overall,a facile,robust and effective strategy is proposed to improve tumor oxygenation by using self-decomposable and biocompatible inorganic nanozyme reactor,which will not only provide an innovative pathway to relieve intratumoral hypoxia,but also present potential applications in other oxygen-favored cancer therapies or oxygen deficiency-originated diseases.

NONINVASIVE OPTICAL IMAGING OF STAPHYLOCOCCUS AUREUS INFECTION IN VIVO USING AN ANTIMICROBIAL PEPTIDE FRAGMENT BASED NEAR-INFRARED FLUORESCENT PROBES

The diagnosis of bacterial infections remains a major challenge in medicine.Optical imaging of bacterial infection in living animals is usually conducted with genetic reporters such as lightemitting encymes or fluorescent proteins.However,there are many circumstances where genetic reporters are not applicable,and there is an urgent need for exogenous synthetic probes that can selectively target bacteria.Optical imaging of bacteria in vivo is much less developed than methods such as ndioimaging and MRI.Furthermore near infrared(NIR)dyes with emision wavelengths in the region of 650-900 rm can propagate through two or more centimeters of tissue and may enable deeper tisue imaging if sensitive detection techniques are employed.Here we constructed an antimicrobial peptide fragment UBI29-41-based near infrared fuorescent imaging probe.The probe is composed of UBI2941 conjugated to a near infraured dye ICG Der-02.UBI29-41 is a cationic antimicrobial peptide that targets the anionic surfaces of bacterial cells.The probe allows detection of Staphylococcus aureus infection(5×10^(7)cells)in a mouse local infection model using whole animal nearinfrared fuorescence imaging.Furthermore,we demonstrate that the UBI29-41-based imaging probe can selectively accumulate within bacteria.The significantly higher accumulation in bacterial infection suggests that UBI29-41-based imaging probe may be a promising imaging agent to detect bacterial infections.

Macrophage as cellular vehicles for delivery of nanoparticles

Treatment of malignant brain tumors continues to challenge scientists and clinicians alike.Location of these tumors within the central nervous system(CNS),which is considered a'privileged" organ,can prevent the penetration of chemotherapeutic agents through the blood-brain barrier(BBB).To overcome this limitation,nanoparticles are taken up and transported bymacrophage and then delivered directly into the CNs.In this study,we used macrophage touptake the folate-targeted bifunctional miclles loaded with near-infrared(NIR)dye ICG-Der-01and investigate the dynamic bio-distributions of macrophage after intravenous injection intotumor-bearing mice.In vitro cellular experiments by confocal microscopy indicated that theuptake of micelles in macrophage was greatly enhanced due to the folate receptor overexpression.Dynamic bio-distributions of macrophage showed a rapid clearing rate through the liver int estine path way.In conclusion,macrophage could potentially be used as nanoparticle drug carriers andrequire further investigation.

PREPARATION AND CHARACTERIZATION OF A NEAR-INFRARED LIGHT RESPONSIVE MICROCAPSULE SYSTEM FOR CANCER THERAPY

A novel near-infrared light responsive microcapsule sy stem,gold nanorod-covered DoX-loadedhollow CaCO;microcapsule(AuNR-HM-DOX)is developed for cancer therapy.The hollowCaCOs microcapsules were prepared based on the selfassembly between chitosan and sodiumalgimate on CaCOs Particles via layer-by-layer technique,and then coveredl with gold nanorods toobtain the microcapsule systemn.Upon near-infrared(NIR)irradiation,microcapsule with goldnanorods can convert the absorbed NIR light into heat.Meanwhile,doxorubicin(DOX),a che.motherapy drug,is loaded into the microcapsule system via electrostatic adsorption for combinedphotothermal therapy and chemotherapy,Properties of AuNR-HM-DOX including grain dia-meter,optical spectra were characterized'Confocal fluorescence imaging was performed to observet he morphology of the capsules and existence of D OX in the core,confrming t he successful loading of DOX.The release of DOX from the capsules under continuous NIR rradiation was investigatedto evaluate the temperat ure responsiveness of AuNR-HMDOX.Results indicate that AuNR-HM.DOX microcapsules possess uniform particle size and high light responsiveness.The combination of chemical and physical therapy of AuNR-HMDOX features great potential as an adjuvanttherapeutic alternative material for combined cancer therapy.

DOX-CONJUGATED HIGH-QUALITY AgZnInS QDs FOR REVERSAL OF MULTIDRUG RESISTANCE

The synthesis of water-soluble quantum dots(QDs)has recently received extensive attention dueto noninvasive detection of biological information in living subjects.In this paper,high-qualitywater-soluble(cadmium-free)quaternary AgZnlnS QDs have been successfully synthesized usinga green synthetic route.The as-prepared QDs exhibit tunable photoluminescence(PL)emissionbetween 521 and 658 nm.Secondly,multidrug resistance(MDR)is a major impedinent to theeffective cancer chemot herapy,DOx,a widely used antit umor drug was modified on the surfaceof the QDs in this study.It,therefore,ignificantly enhanced the cytotoxicity of DX to MDRcancer cells as the QDs could bring the DoX to nucleus.

Tumor-targeted metabolic inhibitor prodrug labelled with cyanine dyes enhances immunoprevention of lung cancer

Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs.To address this challenge,we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug,specifically 6-diazo-5-oxo-L-norleucine(DON),using a thioketal linkage(TK).This system enables imaging,chemotherapy,photodynamic therapy,and on-demand drug release upon radiation exposure.The optimized prodrug,DON-TK-BM3,incorporating cyanine dyes as the fluorophore,displayed potent reactive oxygen species release and efficient tumor cell killing.Unlike the parent drug DON,DON-TK-BM3 exhibited no toxicity toward normal cells.Moreover,DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects,including gastrointestinal toxicity,in mice.This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.