Biomineralization of Versatile CuS/Gd2O3 Hybrid Nanoparticles for MR Imaging and Antitumor Photothermal Chemotherapy

The versatile application of nanoparticles in integrating imaging and therapy has aroused extensive research interest in precision medicine. Of the various nanoparticles that have been studied, CuS has shown great potential in the construction of multifunctional agents, owing to its excellent photothermal heating properties. Herein, we report a facile one‐pot biomineralization approach for the preparation of versatile bovine‐serum‐albumin‐conjugated CuS/Gd₂O₃ hybrid nanoparticles (BSA?CuS/Gd₂O₃ HNPs), which simultaneously possessed strong longitudinal relaxivity, an outstanding photothermal effect, high drug‐loading capacity, and pH/temperature‐responsive drug release. The versatile nanoparticles were used for magnetic resonance imaging (MRI) and antitumor photothermal chemotherapy, both in vitro and in vivo. In vivo MRI showed that the BSA?CuS/Gd₂O₃ HNPs had a long circulation time and effective passive tumor‐uptake ability. More importantly, combined in vitro and in vivo therapy demonstrated that drug‐loaded BSA?CuS/Gd₂O₃ HNPs offered outstanding synergistic therapeutic efficacy for tumor inhibition.     

Copper Sulfide Nanoparticles with Phospholipid‐PEG Coating for In Vivo Near‐Infrared Photothermal Cancer Therapy

In this work, small sizes of hydrophobic copper sulfide nanoparticles (CuS NPs, ～3.8 nm in diameter) have been successfully prepared from the reaction of copper chloride with sodium diethyldithiocarbamate (SDEDTC) inside a heated oleylamine solution. These CuS NPs displayed strong absorption in the 700–1100 nm near‐infrared (NIR) region. By coating CuS NPs with DSPE‐PEG2000 on the surface, the as‐synthesized CuS@DSPE‐PEG NPs exhibited good water solubility, significant stability and biocompatibility, as well as excellent photothermal conversion effects upon exposure to an 808 nm laser. After intravenous administration to mice, the CuS@DSPE‐PEG NPs were found to passively target to the tumor site, and tumor tissues could be ablated efficiency under laser irradiation. In addition, CuS@DSPE‐PEG NPs do not show significant toxicity by histological and blood chemistry analysis, and can be effectively excreted via metabolism. Our results indicated that CuS@DSPE‐PEG NPs can act as an ideal photothermal agent for cancer photothermal therapy.     

A photosensitizer-loaded zinc oxide-polydopamine core-shell nanotherapeutic agent for photodynamic and photothermal synergistic therapy of cancer cells

In clinical cancer research,it is quite promising to develop multimodal synergistic therapeutic strategies.Photodynamic and photothermal synergistic therapy is a very desirable multimodal therapy strategy.Herein,we report a facile and simple method to construct a nanotherapeutic agent for photodynamic and photothermal therapy.This nanotherapeutic agent(ZnO@Ce6-PDA)is composed of a ZnO nanoparticle core,an interlayer of photosensitizer chlorin e6(Ce6)and an outer layer of polydopamine(PDA).Due to the existence of Ce6,the ZnO@Ce6-PDA can efficiently generate singlet oxygen(1O2)under 660 nm laser irradiation.Moreover,the ZnO@Ce6-PDA can serve as a photothermal agent,because of the excellent photothermal conversion efficiency of the PDA coating layer in the presence of 780 nm laser.Experiment results demonstrated that the designed nanotherapeutic agent had outstanding phototoxicity upon the combination of laser irradiation at 660 and 780 nm.Thus,our work proves that the ZnO@Ce6-PDA is a promising photodynamic/photothermal dual-modal nanotherapeutic agent for enhanced cancer therapy.     

A chelator-free multifunctional [64Cu]CuS nanoparticle platform for simultaneous micro-PET/CT imaging and photothermal ablation therapy

We synthesized and evaluated a novel class of chelator-free [(64)Cu]CuS nanoparticles (NPs) suitable both for PET imaging and as photothermal coupling agents for photothermal ablation. These [(64)Cu]CuS NPs are simple to make, possess excellent stability, and allow robust noninvasive micro-PET imaging. Furthermore, the CuS NPs display strong absorption in the near-infrared (NIR) region (peak at 930 nm); passive targeting prefers the tumor site, and mediated ablation of U87 tumor cells occurs upon exposure to NIR light both in vitro and in vivo after either intratumoral or intravenous injection. The combination of small diameter (～11 nm), strong NIR absorption, and integration of (64)Cu as a structural component makes these [(64)Cu]CuS NPs ideally suited for multifunctional molecular imaging and therapy.     

Multifunctional Nanoplatform Based on pH-responsive Micelle Coated with Discontinuous Gold Shell for Cancer Photothermo-chemotherapy and Photoacoustic Tomography

Photothermo-chemotherapy, as a new strategy for cancer treatment, incorporates the complementary advantages of photothermal therapy and chemotherapy. In this study, a pH-sensitive diblock copolymer poly(aspartic acid-butanediamine)-poly(2-(diisopropylamino)ethyl methacrylate) (PAsp(DAB)-PDPA) was synthesized and self-assembled into doxorubicin-loaded micelle, which was further used as a template to form a gold nanoshell. After further modification with poly(ethylene glycol), the resulting nanoplatform provided good biocompatibility and desirable photo-thermal conversion efficiency to facilitate photothermal therapy. Meanwhile the nanoparticle also exhibited pH sensitivity, which prevented drug loss while circulating in the blood but enabled rapid drug release after endocytosis. An improved effect was achieved with the combination of photothermal therapy and chemotherapy. In addition, systemic delivery of the nanoplatform could be monitored by photoacoustic tomography. Thereby, this multifunctional nanoplatform would be highly potential for the diagnosis and therapy of cancer.     

Polyethylene glycol phospholipids encapsulated silicon 2,3-naphthalocyanine dihydroxide nanoparticles (SiNcOH-DSPEPEG(NH2) NPs) for single NIR laser induced cancer combination therapy

Currently, the combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has emerged as a powerful technique for cancer treatment. However, most examples of combined PTT and PDT reported use multi-component nanocomposites under excitation of separate wavelength, resulting in complex treatment process. In this work, a novel theranostic nanoplatform (SiNcOH-DSPE-PEG(NH₂) NPs) has been successfully developed by coating silicon 2,3-naphthalocyanine dihydroxide (SiNcOH) with DSPE-PEG and DSPE-PEG-NH₂ for photoacoustic (PA) imaging-guided PTT and PDT tumor ablation for the first time. The as-prepared single-agent SiNcOH-DSPE-PEG(NH₂) NPs not only have good water solubility and biocompatibility, but also exhibit high photothermal conversion efficiency and singlet oxygen generation capability upon 808 nm NIR laser irradiation. In addition, owing to their high absorption at NIR region, the SiNcOH-DSPE-PEG(NH₂) NPs can also be employed as an effective diagnostic nanoagent for photoacoustic (PA) imaging. In vitro and in vivo experimental results clearly indicated that the simultaneously combined PTT and PDT under the guidance of PA imaging with single NIR laser excitation can effectively kill cancer cells or eradicate tumor tissues. Taking facile synthesis and high efficiency in cancer treatment by SiNcOH-DSPE-PEG(NH₂) NPs into consideration, our study provides a promising strategy to realize molecular imaging-guided combination therapy.     

Dual‐Targeted Selenium Nanoparticles for Synergistic Photothermal Therapy and Chemotherapy of Tumors

A combination of chemo‐ and photothermal therapy has emerged as a promising tactic for cancer therapy. However, the intricacy of accurate delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle. Hence, to assure that the chemotherapeutic drug and photothermal agent are synchronously delivered to a tumor area for their synergistic effect, dual‐target (RC‐12 and PG‐6 peptides) functionalized selenium nanoparticles loaded with both doxorubicin (DOX) and indocyanine green (ICG) were designed and successfully synthesized. The as‐synthesized nanoparticles exhibited good monodispersity, size stability, and consistent spectral characteristics compared with those of ICG or DOX alone. The nanoparticles underwent self‐immolated cleavage under irradiation from a near‐IR laser and released the loaded drug owing to sufficient hyperthermia. Moreover, the internalized nanoparticles triggered the overproduction of intracellular reactive oxygen species to induce cell apoptosis. Taken together, this study provides a sequentially triggered nanosystem to achieve precise drug delivery by chemo‐photothermal combination.     

NIR‐Induced Disintegration of CuS‐Loaded Nanogels for Improved Tumor Penetration and Enhanced Anticancer Therapy

Nanocarrier‐based cancer therapy suffers from poor tumor penetration and unsatisfied therapeutical efficacy, as its vascular extravasation efficiency is often compromised by the intrinsic physiological heterogeneity in tumor tissues. In this work, novel near infrared (NIR)‐responsive CuS‐loaded nanogels are prepared to deliver anticarcinogen into the tumor. These hybrid polymeric nanogels possess high photothermal conversion efficiency, and are able to load a large amount of antitumor drug (e.g., doxorubicin [DOX]). More importantly, the thermal heat could induce self‐destruction of the big‐size framework of hybrid nanogels into small nanoparticles, which greatly facilitates tumor penetration to release DOX deep inside the tumor, as validated by photoacoustic (PA) imaging which exhibits 26.3 times enhancement at the interior region compared to signals of groups without laser irradiation. Such structural alteration, combined with strong photothermal and chemotherapy effects, leads to remarkable inhibition of tumor growth in mice. As a result, this NIR‐induced disintegration of CuS‐loaded nanogels provides a novel drug delivery strategy and might open a new window for clinical cancer treatment.     

Catalytic immunotherapy-photothermal therapy combination for melanoma by ferroptosis-activating vaccine based on artificial nanoenzyme

Tumor cell vaccine is a promising approach for cancer therapy to activate tumor immune, which can be achieved by tumor cells immunogenic cell death (ICD), converting in situ tumors into endogenous vaccination strategy, and ferroptosis has been proved to induce ICD occurrence. Ferroptosis is triggered by artificial nanoenzyme copper telluride mimicking peroxidase and glutathione oxidase, based on which the ferroptosis-activating vaccine (termed as CM CTNPs@OVA) was designed and established for catalytic immunotherapy. Owing to photothermal effect of copper telluride, photothermal therapy (PTT) was combined for an intensive cancer therapeutic effect. CM CTNPs@OVA was composed of solid mesoporous copper telluride nanoparticles, ovalbumin (OVA) loaded in mesoporous, and melanoma cell membrane coating surface. In in vitro and in vivo investigations, CM CTNPs@OVA, with particle size of 113.7 ± 1.7 nm, was certified to release copper ions for ferroptosis initiation, and OVA directly maturated dendritic cell (DC) as exogenous antigens extracellularly. ICD was then induced by ferroptosis pathway and PTT to release damage-associated molecular patterns for DC maturation and subsequent T cells recruitment. CM CTNPs@OVA-treated melanoma with exited inhibition rate, proving that the strategy of catalytic immunotherapy-PTT combination by ferroptosis-activating vaccine possessed massive potential for melanoma therapy based on nanoenzyme copper telluride.     

Magnetic Mesoporous Silica Nanoparticles Cloaked by Red Blood Cell Membranes: Applications in Cancer Therapy

Targeted drug delivery is an emerging technological strategy that enables nanoparticle systems to be responsive for tumor therapy. Magnetic mesoporous silica nanoparticles (MMSNs) were cloaked with red blood cell membrane (RBC). This integrates long circulation, photosensitizer delivery, and magnetic targeting for cancer therapy. In vivo experiments demonstrate that RBC@MMSNs can avoid immune clearance and achieve magnetic field (MF)‐induced high accumulation in a tumor. When light irradiation is applied, singlet oxygen rapidly generates from hypocrellin B (HB)‐loaded RBC@MMSN and leads to the necrosis of tumor tissue. Such a RBC‐cloaked magnetic nanocarrier effectively integrates immunological adjuvant, photosensitizer delivery, MF‐assisted targeting photodynamic therapy, which provides an innovative strategy for cancer therapy.     

适体功能化的金纳米棒用于癌症靶向治疗的研究进展

金纳米棒(gold nanorods,GNRs)具有特殊的光学性质、较大的比表面积、出色的光热转换性能、表面易修饰等特点,在药物递送、光疗、生物成像和化学传感等领域应用十分广泛。适体是短的单链DNA或RNA片段,可特异性识别癌细胞或其表面的膜蛋白。近年来,适体功能化的GNRs在癌症靶向治疗领域显示出良好的应用前景。根据GNRs对癌症作用机制的差异,本文从光热疗法、光动力疗法、化疗和联合疗法4个方面总结了适体功能化的GNRs在癌症靶向治疗中的最新进展,并对该领域面临的主要挑战和发展趋势进行了探讨与展望。     

近红外响应硫化铜纳米粒子/液晶弹性体复合材料研究

报道了一种新型近红外响应光热转换试剂/液晶弹性体复合材料.目前绝大多数近红外吸收的无机金属纳米粒子,由于自身或其稳定剂(如长链硫醇或季铵盐)的化学性质,会致使经典的Finkelmann两步硅氢化加成反应中所使用的催化剂中毒失活,从而极大地限制了无机金属纳米粒子/液晶弹性体复合材料的拓展与应用.为了解决这一科学问题,我们采用了两步硫醇-烯点击化学快速制备单畴取向液晶弹性体薄膜的技术,将对近红外光有强吸收的油溶性硫化铜纳米粒子,成功地掺杂入聚硅氧烷液晶弹性体体系中,制备了近红外响应的硫化铜纳米粒子/液晶弹性体复合薄膜.通过使用紫外可见光谱、透射电子显微镜、扫描电子显微镜、偏光显微镜、示差扫描量热法、变温广角X射线散射对该复合材料进行了深入的研究,结果表明:该薄膜材料在980 nm近红外光源的照射下,可以实现高效的光热转换,从而实现快速、可逆的二维伸缩运动.     

Cell Membrane-Coated Halloysite Nanotubes for Target-Specific Nanocarrier for Cancer Phototherapy

Naturally-occurring halloysite nanotubes (HNTs) have many advantages for constructing target-specific delivery of phototherapeutic agents. Here, HNTs were labeled with fluorescein isothiocyanate (FITC) and loaded with the type-II photosensitizer indocyanine green (ICG) for phototherapy. HNTs-FITC-ICG was structurally stable due to presence of HNTs as the nanocarrier and protective agent. The nanocarrier was further wrapped with red blood cell membrane (RBCM) to enhance the biocompatibility. The HNTs-FITC-ICG-RBCM nanocarrier show high cytocompatibility and hemocompatibility. Due to the photothermal effect of ICG, a significant temperature rising was achieved by irradiation of the nanocarrier using 808 nm laser. The photothermal temperature rising was used to kill the cancer cells effectively. The HNTs-FITC-ICG-RBCM nanocarrier was further linked with anti-EpCAM to endow it with targeting therapy performance against breast cancer, and the anti-EpCAM-conjugated nanocarrier exhibited significantly tumor-specific accumulation. The RBCM-coated and biocompatible HNTs nanocarrier is a promising candidate for target-specific therapy of cancer.     

血红蛋白/光敏剂复合药物体系用于光动力治疗

通过等电点法实现了血红蛋白(Hb)与光敏剂药物七甲川花菁类小分子:11-氯-1,1'-二正丙基-3,3,3',3'-四甲基-10,12-三亚甲基吲哚三碳花青碘盐(IR780)的共担载,并研究了Hb供氧治疗与光动力治疗的联合治疗效果。 通过透射电子显微镜和动态光散射研究了Hb/IR780复合药物载体的形貌与稳定性,证明了药物载体在生理条件下能够稳定存在。 通过对药物在体外溶液和细胞水平的活性氧(ROS)检测,验证了Hb供氧能够有效地促进光敏剂ROS的产生,并且细胞毒性实验也证实了Hb/IR780复合药物载体拥有比单组份IR780药物更明显的肿瘤细胞杀伤效果。     

银纳米粒子修饰的二维金属-有机框架纳米片用于光热增强银离子释放抗菌

近年来,二维(2D)金属-有机框架(MOF)纳米复合材料被广泛的应用于生物医学领域,尤其是在抗菌方面。在此,我们通过光照诱导还银离子成功在二维MOF纳米片上生长银纳米粒子,得到了一种银纳米粒子(Ag NPs)修饰的二维Zr-Fc-MOF (MOF-Ag)纳米片,并将其用于光热增强Ag⁺释放抗菌治疗。通过水热法和超声处理合成MOF纳米片,然后通过原位光辐照诱导还原在MOF纳米片上生长Ag NPs。系列表征结果表明Ag NPs成功负载到MOF纳米片上。聚乙烯吡咯烷酮(PVP)的修饰不仅可以增强MOF-Ag在溶液中的稳定性,还可以增强它的生物相容性。在近红外激光(NIR)照射下,MOF纳米片可以在短时间升温,而温度的升高可以加速Ag NPs在溶液中氧化为银离子。通过细菌生长曲线、菌落相对数和细菌形态变化等实验表明PVP@MOF-Ag纳米片具有优异的广谱杀菌性能。此外,2D MOF纳米片良好的光热性能不仅可以增强Ag⁺的释放,还可以增强细胞膜的通透性,随后进入细菌中的Ag⁺可以诱导内源性活性氧的产生,从而引发细菌的氧化应激,实现高效抗菌。基于良好的体外抗菌性能,进一步将PVP@MOF-Ag纳米片用于小鼠伤口愈合,在此期间PVP@MOF-Ag纳米片表现出良好的治疗效果和生物安全性。我们的研究结果表明,PVP@MOF-Ag纳米片可以作为光热增强Ag⁺释放抗菌治疗和伤口愈合的有效平台。     

Platelet‐Facilitated Photothermal Therapy of Head and Neck Squamous Cell Carcinoma

Here, we present a platelet‐facilitated photothermal tumor therapy (PLT‐PTT) strategy, in which PLTs act as carriers for targeted delivery of photothermal agents to tumor tissues and enhance the PTT effect. Gold nanorods (AuNRs) were first loaded into PLTs by electroporation and the resulting AuNR‐loaded PLTs (PLT‐AuNRs) inherited long blood circulation and cancer targeting characteristics from PLTs and good photothermal property from AuNRs. Using a gene‐knockout mouse model, we demonstrate that the administration of PLT‐AuNRs and localizing laser irradiation could effectively inhibit the growth of head and neck squamous cell carcinoma (HNSCC). In addition, we found that the PTT treatment augmented PLT‐AuNRs targeting to the tumor sites and in turn, improved the PTT effects in a feedback manner, demonstrating the unique self‐reinforcing characteristic of PLT‐PTT in cancer therapy.     

Determination of the minimum temperature required for selective photothermal destruction of cancer cells with the use of immunotargeted gold nanoparticles

Laser photothermal therapy of cancer with the use of gold nanoparticles immunotargeted to molecular markers on the cell surface has been shown to be an effective modality to selectively kill cancer cells at much lower laser powers than those needed for healthy cells. To elucidate the minimum light dosimetry required to induce cell death, photothermal destruction of two cancerous cell lines and a noncancerous cell line treated with antiepidermal growth factor receptor (anti-EGFR) antibody-conjugated gold nanoparticles is studied, and a numerical heat transport model is used to estimate the local temperature rise within the cells as a result of the laser heating of the gold nanoparticles. It is found that cell samples with higher nanoparticle loading require a lower incident laser power to achieve a certain temperature rise. Numerically estimated temperatures of 70-80 degrees C achieved by heating the gold particles agree well with the measured threshold temperature for destruction of the cell lines by oven heating and those measured in an earlier nanoshell method. Specific binding of anti-EGFR antibody to cancerous cells overexpressing EGFR selectively increases the gold nanoparticle loading within cancerous cells, thus allowing the cancerous cells to be destroyed at lower laser power thresholds than needed for the noncancerous cells. In addition, photothermal therapy using gold nanoparticles requires lower laser power thresholds than therapies using conventional dyes due to the much higher absorption coefficient of the gold nanoparticles.     

Self-assembled all-inclusive organic-inorganic nanoparticles enable cascade reaction for the detection of glucose

Traditional colorimetric glucose biosensor generally involves complex assay procedures. Free labile enzymes and peroxidase substrates are used separately for triggering a chromogenic reaction. These limits result in inferior enzyme stability and defective enzymatic catalytic efficiency, making it hard to routinely utilize them for the direct and fast test of glucose. In this work, we provide an all-inclusive substrates/enzymes nanoparticle employed 3,3′5,5′-tetramethylbenzidine (TMB) as chromogenic substrates and glucose oxidase (GOx)/horseradish peroxidase (HRP) as signal amplifier enzymes (TMB-GH NPs) by the molecule self-assembly technique. The “all-inclusive” nanoparticles can realize the tandem colorimetric reactions, and the oxidation product of TMB (ox-TMB) exhibits a strong NIR laser-driven photothermal effect, thus allowing quantitative photothermal detection of glucose. Owing to the restriction of the molecular motion of GOx, HRP, and TMB, the distance of mass transfer between substrates was shortened largely, leading to improved catalytic activity for glucose. Overall, our strategy will simplify the analysis procedure, furthermore, these integrated nanoparticles not only display higher stability and activity than that of the free GOx/HRP system and possesses an excellent performance for colorimetric and photothermal bioassay of glucose simultaneously. We believe that this unique technique will give good inspirations to develop simple and precise methods for bioassay.     

Stimuli-responsive dual drugs-conjugated polydopamine nanoparticles for the combination photothermal-cocktail chemotherapy

We developed one-pot aqueous copolymerization of two dopamine prodrugs to prepare dual drugsconjugated polydopamine nanoparticles(PDOXCBs),which integrated near infrared(NIR)-mediated photothermal effect with cocktail chemotherapy into one copolymer nanoparticle.Upon a mild NIR irradiation(808 nm,1 W/cm²,10 min),PDOXCBs gradually heated aqueous solution over 12.8-13.9℃,which accordingly enhanced in vitro dual doxorubicin(DOX) and chlorambucil(CB) drug-release with assistance of the other stimuli of pH 5.0 and 10 mmol/L D,L-dithiothreitol(DTT).The combination photothermal-cocktail chemotherapy(PTT-CCT) treatment based on PDOXCB27 plus NIR irradiation gave a highly lowered half maximal inhibitory concentration(IC₅₀) of 2.23 μg/mL and a combination index of0.36,displaying a superior synergistic effect between PTT and CCT in vitro.     

Black Pigment Gallstone Inspired Platinum‐Chelated Bilirubin Nanoparticles for Combined Photoacoustic Imaging and Photothermal Therapy of Cancers

Bilirubin (BR), a bile pigment that exerts potent antioxidant and anti‐inflammatory effects, is also a major constituent of black pigment gallstones found in bile ducts under certain pathological conditions. Inspired by the intrinsic metal‐chelating power of BR found in gallstones, herein we report a cisplatin‐chelated BR‐based nanoparticle (cisPt@BRNP) for use as a new photonic nanomedicine for combined photoacoustic imaging and photothermal therapy of cancers. The cisPt@BRNPs were prepared by simply mixing cisplatin with BRNPs, yielding ca. 150‐nm‐size NPs. Upon near‐IR laser irradiation at 808 nm, cisPt@BRNPs generated considerable heat and induced clear death of cancer cells in vitro. Following intravenous injection into human colon cancer‐bearing mice, cisPt@BRNPs allowed effective tumor visualization by photoacoustic imaging and remarkable antitumor efficacy by photothermal therapy, suggesting their potential for use as a new photonic nanomedicine for cancer therapy.