A biomimetic spore nanoplatform for boosting chemodynamic therapy and bacteria-mediated antitumor immunity for synergistic cancer treatment

Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer.However,the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations.Furthermore,monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors.In this study,based on our discovery that spore shell(SS)of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity,we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy,chemodynamic therapy and antitumor immunity for synergistic cancer treatment.In detail,SS is separated from probiotic spores and then attached to the surface of liposome(Lipo)that was loaded with hemoglobin(Hb),glucose oxidase(GOx)and JQ1to construct SS@Lipo/Hb/GOx/JQ1.In tumor tissue,highly toxic hydroxyl radicals(·OH)are generated via sequential catalytic reactions:GOx catalyzing glucose into H_(2)O_(2)and Fe^(2+)in Hb decomposing H_(2)O_(2)into·OH.The combination of·OH and SS adjuvant can improve tumor immunogenicity and activate immune system.Meanwhile,JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response.In this manner,SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis.To summarize,the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.

Temperature-feedback two-photon-responsive metal-organic frameworks for efficient photothermal therapy

The realization of real-time thermal feedback for monitoring photothermal therapy(PTT)under near-infrared(NIR)light irradiation is of great interest and challenge for antitumor therapy.Herein,by assembling highly efficient photothermal conversion gold nanorods and a temperature-responsive probe((E)-4-(4-(diethylamino)styryl)-1-methylpyridin-1-ium,PyS)within MOF-199,an intelligent nanoplatform(AMPP)was fabricated for simultaneous chemodynamic therapy and NIR light-induced temperature-feedback PTT.The fluorescence intensity and temperature of the PyS probe are linearly related due to the restriction of the rotation of the characteristic monomethine bridge.Moreover,the copper ions resulting from the degradation of MOF-199 in an acidic microenvironment can convert H_(2)O_(2)into•OH,resulting in tumor ablation through a Fenton-like reaction,and this process can be accelerated by increasing the temperature.This study establishes a feasible platform for fabricating highly sensitive temperature sensors for efficient temperature-feedback PTT.

Targeting nanoplatform synergistic glutathione depletion-enhanced chemodynamic,microwave dynamic,and selective-microwave thermal to treat lung cancer bone metastasis

Once bone metastasis occurs in lung cancer,the efficiency of treatment can be greatly reduced.Current mainstream treatments are focused on inhibiting cancer cell growth and preventing bone destruction.Microwave ablation(MWA)has been used to treat bone tumors.However,MWA may damage the surrounding normal tissues.Therefore,it could be beneficial to develop a nanocarrier combined with microwave to treat bone metastasis.Herein,a microwave-responsive nanoplatform(MgFe_(2)O_(4)@ZOL)was constructed.MgFe_(2)O_(4)ZOL NPs release the cargos of Fe^(3+),Mg^(2+)and zoledronic acid(ZOL)in the acidic tumor microenvironment(TME).Fe^(3+)can deplete intracellular glutathione(GSH)and catalyze H_(2)O_(2)to generate•OH,resulting in chemodynamic therapy(CDT).In addition,the microwave can significantly enhance the production of reactive oxygen species(ROS),thereby enabling the effective implementation of microwave dynamic therapy(MDT).Moreover,Mg^(2+)and ZOL promote osteoblast differentiation.In addition,MgFe_(2)O_(4)ZOL NPs could target and selectively heat tumor tissue and enhance the effect of microwave thermal therapy(MTT).Both in vitro and in vivo experiments revealed that synergistic targeting,GSH depletion-enhanced CDT,MDT,and selective MTT exhibited significant antitumor efficacy and bone repair.This multimodal combination therapy provides a promising strategy for the treatment of bone metastasis in lung cancer patients.

Boosting Chemodynamic Therapy by the Synergistic Effect of Co‑Catalyze and Photothermal Effect Triggered by the Second Near‑Infrared Light

In spite of the tumor microenvironments responsive cancer therapy based on Fenton reaction(i.e.,chemodynamic therapy,CDT)has been attracted more attentions in recent years,the limited Fenton reaction efficiency is the important obstacle to further application in clinic.Herein,we synthesized novel FeO/MoS2 nanocomposites modified by bovine serum albumin(FeO/MoS2-BSA)with boosted Fenton reaction efficiency by the synergistic effect of co-catalyze and photothermal effect of MoS2 nanosheets triggered by the second near-infrared(NIR II)light.In the tumor microenvironments,the MoS2 nanosheets not only can accelerate the conversion of Fe3+ions to Fe2+ions by Mo4+ions on their surface to improve Fenton reaction efficiency,but also endow FeO/MoS2-BSA with good photothermal performances for photothermal-enhanced CDT and photothermal therapy(PTT).Consequently,benefiting from the synergetic-enhanced CDT/PTT,the tumors are eradicated completely in vivo.This work provides innovative synergistic strategy for constructing nanocomposites for highly efficient CDT.

Self-Assembly Protein Superstructures as a Powerful Chemodynamic Therapy Nanoagent for Glioblastoma Treatment

Glioblastoma(GBM) remains a formidable challenge in oncology.Chemodynamic therapy(CDT) that triggers tumor cell death by reactive oxygen species(ROS) could open up a new door for GBM treatment.Herein,we report a novel CDT nanoagent.Hemoglobin(Hb)and glucose oxidase(GOx) were employed as powerful CDT catalysts.Instead of encapsulating the proteins in drug delivery nanocarriers,we formulate multimeric superstructures as self-delivery entities by crosslinking techniques.Red blood cell(RBC) membranes are camouflaged on the protein superstructures to promote the delivery across blood-brain barrier.The as-prepared RBC@Hb@GOx nanoparticles(NPs) offer superior biocompatibility,simplified structure,and high accumulation at the tumor site.We successfully demonstrated that the NPs could efficiently produce toxic ROS to kill U87 MG cancer cells in vitro and inhibit the growth of GBM tumor in vivo,suggesting that the new CDT nanoagent holds great promise for treating GBM.

Cytochrome-c aptamer functionalized Pt nanoclusters for enhanced chemodynamic therapy

Catalysis-based chemodynamic therapy(CDT)is an emerging cancer treatment strategy which uses a Fenton-like reaction to kill tumor cells by catalyzing endogenous hydrogen peroxide(H_(2)O_(2))into a toxic hydroxyl radical(·OH).The performance of CDT is greatly dependent on PDT agent.Herein,mitochondria-targeting Pt nanoclusters were synthesized using cytochrome c aptamer(CytcApt)as template.The obtained CytcApt-PtNCs can produce.OH by H_(2)O_(2)under the acidic conditions.Moreover,CytcApt-PtNCs could kill 4T1 tumor cells in a pH-dependent manner,but had no side effect on normal 293T cells.Therefore,CytcApt-PtNCs possess excellent therapeutic effect and good biosafety,indicating their great potential for CDT.

近红外光响应性纳米颗粒h-PCuNF介导多模态疗法治疗恶性肿瘤

背景:基于多功能纳米材料的精准治疗是恶性肿瘤的新型治疗模式,多功能纳米材料可以将多种成像和治疗模式整合到一个纳米级平台中,实现可视化联合治疗。目的:制备载碱式磷酸铜纳米颗粒和荷叶碱的新型纳米颗粒h-PCuNF,探讨其介导光热/光动力/化学动力/化疗联合治疗肿瘤的能力。方法:采用双乳化法将碱式磷酸铜纳米颗粒和荷叶碱搭载到中空聚乳酸-羟基乙酸共聚物纳米载体的壳层中,制备出新型纳米颗粒h-PCuNF,表征该纳米颗粒的形态、结构、粒径、Zeta电位等。在去离子水中,检测该纳米颗粒的MRI成像、光热转换及介导光催化和类芬顿反应产生活性氧的能力。在肝脏恶性肿瘤细胞系HepG2中,采用荧光成像和MTT法检测纳米颗粒h-PCuNF介导光热/光动力/化学动力/化疗联合治疗肿瘤的能力。结果与结论:①纳米颗粒h-PCuNF呈中空球形结构,壳层中搭载有碱式磷酸铜纳米颗粒(载药率和包封率分别为26.3%和63.2%)和荷叶碱(载药率和包封率分别为11.0%和52.6%),平均粒径为(309.2±10.0)nm,Zeta电位为(-12.5±0.9)mV,在生理环境中具有良好的悬浮稳定性。②在去离子水中,纳米颗粒h-PCuNF可以显著增强T1加权MRI成像;在近红外激光照射下,纳米颗粒h-PCuNF具有良好的光热转换和光催化活性氧生成的能力;此外,纳米颗粒h-PCuNF可以消耗谷胱甘肽并介导类芬顿反应产生•OH。③纳米颗粒h-PCuNF可被肿瘤细胞HepG2摄取,并且主要分布在细胞质中;纳米颗粒h-PCuNF被近红外激光照射激活后,碱式磷酸铜纳米颗粒介导的光热/光动力/化学动力治疗可与荷叶碱介导的化疗协同治疗恶性肿瘤。

MB-SF/cRGD的合成及其化学动力学抗肿瘤研究

化学动力学治疗(CDT)具有一定的抗肿瘤效果,但由于肿瘤微环境(TME)的复杂性,导致药物无法高效积聚到肿瘤部位,从而无法达到满意的治疗效果.先通过水解与提纯得到丝素蛋白,再通过酰胺化反应在丝素蛋白表面连接cRGD,最后加入Bi(NO_(3))·5H_(2)O和MnCl_(2)·4H_(2)O,搅拌过夜获得MB-SF/cRGD.设计了一种具有主动靶向能力的CDT治疗体系,旨在通过提高癌症细胞药物摄取率,加强化学动力学治疗效果.丝素蛋白作为一种具有良好生物相容性和降解性的药物载体,可以有效改善药物递送系统引起的生物相容性差等问题;MnO_(2)利用内源性H_(2)O_(2)实现化学动力学治疗、消耗GSH以及产生O_(2),发挥抗肿瘤疗效.此外,在药物表面修饰cRGD不但可以减少对正常细胞的毒性,还可以提高化学动力学治疗的价值.实验结果表明:利用MB-SF本身的活性能达到一定的抗肿瘤疗效,在此基础上,修饰有主动靶向癌细胞的cRGD所获得的MB-SF/cRGD能达到更好的肿瘤治疗效果.

金属-有机骨架在肿瘤化学动力学治疗中的应用

目前,肿瘤常用的治疗方法有化疗(CT)、放疗(RT)、手术切除等,但治疗效果相对有限且伴有严重的副作用,迫切需要开发新型的治疗方式。化学动力学疗法(CDT)是一种基于芬顿(类芬顿)反应的新型治疗方法,与其他治疗方式相比,CDT不需要借助光源或外界能量来引发,具有全身副作用更小等优势。CDT利用Fe^(2+)、Cu^(2+)或其他金属离子(Mn^(2+)、Zn^(2+)、Co^(2+))与肿瘤微环境(TME)中过量的过氧化氢(H_(2)O_(2))反应,形成高细胞毒性的羟基自由基(·OH)来杀死癌细胞。因此,CDT这一通过原位产生·OH的非侵入性肿瘤疗法已被广泛用于肿瘤治疗。金属有机骨架(MOFs)是一类由金属离子和有机配体配位自组装而成的多空晶体结构,因其高孔隙率、大比表面积、多金属催化位点和优异的生物相容性等特点在CDT治疗研究领域备受关注。本文介绍了不同MOFs在肿瘤CDT治疗中的作用及提高CDT治疗效果常用的物理和化学手段。此外,根据目前的研究进展,提出了CDT未来的发展和挑战,希望能够为CDT的研究提供新思路。

Valence-tailored copper-based nanoparticles for enhanced chemodynamic therapy through prolonged ROS generation and potentiated GSH depletion

Chemodynamic therapy(CDT),an inventive approach to cancer treatment,exploits innate chemical processes to trigger cell death through the generation of reactive oxygen species(ROS).While offering advantages over conventional treatments,the optimization of CDT efficacy presents challenges stemming from suboptimal catalytic efficiency and the counteractive ROS scavenging effect of intracellular glutathione(GSH).In this study,we aim to address this dual challenge by delving into the role of copper valence states in CDT.Leveraging the unique attributes of copper-based nanoparticles,especially zero-valent copper nanoparticles(CuPd NPs),we aim to enhance the therapeutic potential of CDT.Our experiments reveal that zero-valent CuPd NPs outperform divalent copper nanoparticles(Ox-CuPd NPs)by displaying superior catalytic performance and sustaining ROS generation through a dual approach integrating peroxidase-like(POD-like)activity and Cu+release.Notably,zero-valent NPs exhibit enhanced GSH depletion compared to their divalent counterparts,thereby intensifying CDT and inducing ferroptosis,ultimately resulting in high-efficiency tumor growth inhibition.These findings reveal the impact of valences on CDT,providing novel insights for the optimization and design of CDT agents.

NIR-switchable local hydrogen generation by tandem bimetallic MOFs nanocomposites for enhanced chemodynamic therapy

The inadequate quantity of hydrogen peroxide(H_(2)O_(2))in cancer cells promptly results in the constrained success of chemodynamic therapy(CDT).Significant efforts made throughout the years;nevertheless,researchers are still facing the great challenge of designing a CDT agent and securing H_(2)O_(2) supply within the tumor cell.In this study,taking advantage of H_(2)O_(2) level maintenance mechanism in cancer cells,a nanozyme-based bimetallic metal-organic frameworks(MOFs)tandem reactor is fabricated to elevate intracellular H_(2)O_(2) levels,thereby enhancing CDT.In addition,under nearinfrared excitation,the upconversion nanoparticles(UCNPs)loaded into the MOFs can perform photocatalysis and generate hydrogen,which increases cellular susceptibility to radicals induced from H_(2)O_(2),inhibits cancer cell energy,causes DNA damages and induces tumor cell apoptosis,thus improving CDT therapeutic efficacy synergistically.The proposed nanozyme-based bimetallic MOFs-mediated CDT and UCNPs-mediated hydrogen therapy act as combined therapy with high efficacy and low toxicity.

用于抑制肿瘤细胞生长的叶酸修饰聚多巴胺涂层的氧化铜纳米颗粒

采用沉淀转化法制备出粒径约为10 nm的氧化铜纳米颗粒(CuO NPs),通过盐酸多巴胺(DA HCl)在其表面进行聚合,并通过叶酸(FA)修饰形成CuO@PDA-FA NPs。采用透射电子显微镜、红外光谱仪、纳米粒径电势分析仪、X射线光电子能谱对纳米颗粒的形貌和性质进行表征。结果表明,制备的CuO@PDA-FA NPs粒径约为190 nm。材料降解亚甲基蓝试验和氧化葡萄糖试验证实CuO@PDA-FA NPs具备类过氧化物酶(POD)活性和类葡萄糖氧化酶(GOD)活性。近红外光热转换试验证实CuO@PDA-FA NPs具有良好的光热效应和光热稳定性。体外细胞毒性试验、细胞摄取试验和活性氧生成试验结果表明,CuO@PDA-FA NPs能主动靶向肿瘤细胞,并通过光热治疗(PTT)/化学动力学治疗(CDT)/饥饿治疗(ST)协同效果杀伤肿瘤细胞。

肢体慢性淋巴水肿CDT治疗后低弹力绷带使用时长对远期疗效的影响

目的探讨肢体慢性淋巴水肿CDT(Complex decongestion therapy)治疗后低弹绷带使用时长对于长期疗效的影响。方法2016至今,对57例淋巴水肿患者按治疗结束后自我使用低弹绷带包扎时长(t)分为A(>1年)、B(0.5~1年)、C(<0.5年)3组。采用多频生物电阻人体成分分析仪测量组织水分,卷尺测量肢体周径。比较3组患者复诊时与治疗结束时水分和周径的变化。结果A组在维持肢体周径、水分方面明显优于B组和C组,B组则优于C组(P<0.05)。3组治疗后的丹毒发作频率均有改善,A组改善最为明显(P<0.05)。结论肢体慢性淋巴水肿患者在CDT治疗结束后应继续使用低弹绷带包扎患肢,坚持使用越久的患者长期疗效越好。

Ternary NiCoTi-layered double hydroxide nanosheets as a pH-responsive nanoagent for photodynamic/chemodynamic synergistic therapy

Combining photodynamic therapy(PDT)with chemodynamic therapy(CDT)has been proven to be a promising strategy to improve the treatment efficiency of cancer,because of the synergistic therapeutic effect arising between the two modalities.Herein,we report an inorganic nanoagent based on ternary NiCoTi-layered double hydroxide(NiCoTi-LDH)nanosheets to realize highly efficient photodynamic/chemodynamic synergistic therapy.The NiCoTi-LDH nanosheets exhibit oxygen vacancy-promoted electron-hole separation and photogenerated holeinduced O_(2)-independent reactive oxygen species(ROS)generation under acidic circumstances,realizing in situ pH-responsive PDT.Moreover,due to the effective conversion between Co^(3+)and Co^(2+)caused by photogenerated electrons,the NiCoTi-LDH nanosheets catalyze the release of hydroxyl radicals(-OH)from H_(2)O_(2)through Fenton reactions,resulting in CDT.Laser irradiation enhances the catalyzed ability of the NiCoTi-LDH nanosheets to promote the ROS generation,resulting in a better performance than TiO_(2)nanoparticles at pH 6.5.In vitro and in vivo experimental results show conclusively that NiCoTi-LDH nanosheets plus irradiation lead to efficient cell apoptosis and significant inhibition of tumor growth.This study reports a new pH-responsive inorganic nanoagent with oxygen vacancy-promoted photodynamic/chemodynamic synergistic performance,offering a potentially appealing clinical strategy for selective tumor elimination.

Nano metal-photosensitizer based on Aza-BODIPY-Cu complex for CDT-enhanced dual phototherapy

Chemodynamic therapy(CDT)combined with dual phototherapy(photothermal therapy(PTT)and photodynamic therapy(PDT))is an efficient way to synergistically improve anti-tumor efficacy.However,the combination of multiple modes often makes the composition of the system more complex,which is not conducive to clinical application.In this study,a dual phototherapy ligand carboxyl-modified Aza-BODIPY(BOD-COOH)and metal active center Cu^(2+)were used to construct multiple-modes metalphotosensitizer nanoparticles(BOD-Cu NPs)via one-step coordination self-assembly for combination therapy of CDT/PDT/PTT.In order to improve delivery efficiency,the targeted hydrophilic molecule pyridinemodified glucose derivative(G-Py)was synthesized and coated onto the BOD-Cu NPs to form a glycosylated nano metal-photosensitizer BOD-Cu@G by electrostatic interaction.The Cu^(2+)in BOD-Cu@G could not only be used as a coordination node for metal-driven self-assembly but also consume intracellular glutathione(GSH),and then catalyze Fenton-like reaction to generate hydroxyl radical(·OH)for CDT.In vitro and in vivo studies revealed that BOD-Cu@G could achieve excellent anti-tumor efficiency by CDTenhanced dual phototherapy.

A Review on Nanomaterial-based Strategies for Manipulating Tumor Microenvironment to Enhance Chemodynamic Therapy

Cancer is a leading cause of death worldwide,and a series of strategies has been reported for tumor-specific therapy.Currently,chemodynamic therapy(CDT)has become a research hotspot for antitumor treatment due to its advantages of high specificity,endogenous stimulation,and high biosafety.However,the therapeutic effects of CDT are normally limited in the complex tumor microenvironment(TME),such as insufficient acidity,tumor hypoxia,low hydrogen peroxide(H2O2),and high glutathione(GSH).Consequently,different kinds of multifunctional nanomaterials have been designed to manipulate TME conditions,which provided more opportunities to improve the efficiency of CDT.This review focuses on nanomaterial-based strategies for enhancing CDT through manipulating TME.Upon CDT enhancements,this review would provide a reference for the future development of efficient CDT nanomaterials.

CRISPR-Cas9 gene editing strengthens cuproptosis/chemodynamic/ferroptosis synergistic cancer therapy

Copper-based nanomaterials demonstrate promising potential in cancer therapy.Cu^(+) efficiently triggers a Fenton-like reaction and further consumes the high level of glutathione,initiating chemical dynamic therapy(CDT)and ferroptosis.Cuproptosis,a newly identified cell death modality that represents a great prospect in cancer therapy,is activated.However,active homeostatic systems rigorously keep copper levels within cells exceptionally low,which hinders the application of cooper nanomaterials-based therapy.Herein,a novel strategy of CRISPR-Cas9 RNP nanocarrier to deliver cuprous ions and suppress the expression of copper transporter protein ATP7A for maintaining a high level of copper in cytoplasmic fluid is developed.The Cu_(2)O and organosilica shell would degrade under the high level of glutathione and weak acidic environment,further releasing RNP and Cu^(+).The liberated Cut triggered a Fenton-like reaction for CDT and partially transformed to Cu^(2+),consuming intracellular GSH and initiating cuproptosis and ferroptosis efficiently.Meanwhile,the release of RNP effectively reduced the expression of copper transporter ATP7A,subsequently increasing the accumulation of cooper and enhancing the efficacy of CDT,cuproptosis,and ferroptosis.Such tumor microenvironment responsive multimodal nanoplatform opens an ingenious avenue for colorectal cancer therapy based on gene editing enhanced synergistic cuproptosis/CDT/ferroptosis.

Adenosine triphosphate-responsive carbon dots nanoreactors for T_(1)-weighted magnetic resonance imaging-guided tumor chemodynamic therapy

There are various strategies to conduct tumor microenvironment(TME)stimulus-responsive(e.g.,acid,H_(2)O_(2)or glutathione)nanoreactors for increasing the efficiency of chemodynamic therapy(CDT).Among these,the exploitation of adenosine triphosphate(ATP,another overexpressed biomarker in TME)-responsive nanoreactors for tumor CDT is still challenging.Herein,the ATP-responsive iron-doped CDs(FeCDs)were firstly prepared and then coassembled with glucose oxidase(GOx)to obtain FeCDs/GOx liposomes as ATP-responsive nanoreactors.Under TME conditions,the nanoreactors initially released FeCDs and GOx.Subsequently,with the existence of ATP,iron ions were rapidly released from the FeCDs to trigger Fenton/Fenton-like reactions for generating·OH.Meanwhile,the T_(1)-weighted magnetic resonance imaging(MRI)was achieved due to the released iron ions.Moreover,the GOx converted endogenous glucose in tumor to gluconic acid and H_(2)O_(2)to satisfy the requirement of·OH generation.In vitro as well as in vivo experiments illustrated that the obtained ATP-responsive CD nanoreactors could be used as a versatile nanotheranostics for simultaneously T_(1)-weighted MRI-guided tumor CDT.This work presents a new ATP-responsive nanoreactor with selfsupplied H_(2)O_(2)for multifunctional nanotheranostic applications.

pH响应铜掺杂介孔硅纳米催化剂增强肿瘤化疗–化学动力学联合治疗的研究

化学动力学疗法(CDT)利用肿瘤细胞内源性H_(2)O_(2)与芬顿催化剂反应生成高毒性的羟基自由基(•OH),从而杀死肿瘤细胞,但内源性H_(2)O_(2)不足和纳米粒子转运效率较低导致抗癌效果不理想。本研究制备了一种分散性良好、尺寸较小的铜掺杂介孔二氧化硅(Cu-MSN),负载化疗药物阿霉素(DOX)和抗坏血酸盐(AA)后,表面经叶酸(FA)和二甲基马来酸酐(DMMA)改性的壳聚糖(FA-CS-DMMA)以及羧甲基壳聚糖(CMC)包裹,得到pH响应型靶向纳米催化剂FA-CS-DMMA/CMC@Cu-MSN@DOX/AA(缩写为FCDC@Cu-MSN@DA)。扫描电镜显示纳米粒子FCDC@Cu-MSN@DA粒径约为100 nm。体外48 h内Cu^(2+)释放量可达80%,药物DOX释放达到57.3%。释放的AA经自氧化后产生H_(2)O_(2),诱导Cu^(2+)发生类芬顿反应,从而增强CDT。细胞实验证明,FCDC@Cu-MSN@DA联合化疗药物表现出优异的抗肿瘤活性,说明该多功能纳米催化剂在癌症治疗中具有潜在应用前景。

磁性介孔纳米材料的制备及性能的研究

通过水热法合成了分散性良好的Fe_(3)O_(4)纳米微球,在其外层包覆了介孔二氧化硅(MSN),并进一步修饰了壳聚糖(CS)和透明质酸(HA),形成了高分散的纳米微球Fe_(3)O_(4)@SiO_(2)@MSN@CS@HA。通过扫描电镜(SEM)、透射电镜(TEM)表征了纳米微球的结构、形貌、粒径及分散性。利用热重分析仪(TGA)和比表面分析仪(BET)测试了其外层含量、比表面积和孔径大小。通过紫外可见光谱分析仪测定了参与芬顿反应的性能,并计算其反应速率。结果表明,纳米微球具有良好的分散性和载药能力,且含有的二价铁离子(Fe^(2+))可以进一步实现肿瘤的化学动力学治疗潜力。