Recent advances in functionalized ferrite nanoparticles: From fundamentals to magnetic hyperthermia cancer therapy.

Cancers are fatal diseases that lead to most death of human beings, which urgently require effective treatments methods. Hyperthermia therapy employs magnetic nanoparticles (MNPs) as heating medium under external alternating magnetic field. Among various MNPs, ferrite nanoparticles (FNPs) have gained significant attention for hyperthermia therapy due to their exceptional magnetic properties, high stability, favorable biological compatibility, and low toxicity. The utilization of FNPs holds immense potential for enhancing the effectiveness of hyperthermia therapy. The main hurdle for hyperthermia treatment includes optimizing the heat generation capacity of FNPs and controlling the local temperature of tumor region. This review aims to comprehensively evaluate the magnetic hyperthermia treatment (MHT) of FNPs, which is accomplished by elucidating the underlying mechanism of heat generation and identifying influential factors. Based upon fundamental understanding of hyperthermia of FNPs, valuable insights will be provided for developing efficient nanoplatforms with enhanced accuracy and magnetothermal properties. Additionally, we will also survey current research focuses on modulating FNPs' properties, external conditions for MHT, novel technical methods, and recent clinical findings. Finally, current challenges in MHT with FNPs will be discussed while prospecting future directions.

Retraction: A novel TMTP1-modified theranostic nanoplatform for targeted in vivo NIR-II fluorescence imaging-guided chemotherapy for cervical cancer.

Retraction of 'A novel TMTP1-modified theranostic nanoplatform for targeted in vivo NIR-II fluorescence imaging-guided chemotherapy for cervical cancer' by Nuernisha Alifu et al., J. Mater. Chem. B, 2022, 10, 506-517, https://doi.org/10.1039/D1TB02481G.

Functionalized Magnetic Nanoparticles for NIR-Induced Photothermal Therapy of Potential Application in Cervical Cancer.

Photothermal therapy (PTT) holds great promise for cancer treatment with its effective ablation of solid tumors. As the essential core point, photothermal agents (PTAs) with excellent photothermal properties and good biocompatibility could help to fulfill highly efficient PTT. Herein, a novel type of nanoplatform Fe3O4@PDA/ICG (FPI) nanoparticle (NP) was designed and synthesized, which was composed of magnetic Fe3O4 and near-infrared excitable indocyanine green via encapsulation of polydopamine. The FPI NPs showed spherical structures in shape with uniform distribution and good chemical stability. Under 793 nm laser irradiation, FPI NPs could generate hyperthermia of 54.1 °C and photothermal conversion efficiency of 35.21%. The low cytotoxicity of FPI NPs was further evaluated and confirmed on HeLa cells with a high survival rate (90%). Moreover, under laser irradiation (793 nm), FPI NPs showed effective photothermal therapeutic characteristics for HeLa cells. Therefore, FPI NPs, as one of the promising PTAs, have great potential in the field of PTT for tumor treatment.

NIR-II fluorescence microscopic bioimaging for intrahepatic angiography and the early detection of Echinococcus multilocularis microlesions.

Hepatic alveolar echinococcosis (HAE) is caused by the metacestode of Echinococcus multilocularis, which shows characteristics of malignant tumors with high mortality. However, traditional diagnostic imaging methods are still not sufficient for the recognition of HAE microlesions in the early stages. Near-infrared-II (900-1700 nm, NIR-II) fluorescence microscopic imaging (NIR-II-FMI) has shown great potential for biomedical detection. A novel type of negative target imaging method based on NIR-II-FMI with the assistance of indocyanine green (ICG) was explored. Then, NIR-II-FMI was applied to the early detection of HAE for the first time. The negative targeting NIR-II fluorescence imaging of HAE-infected mice at different stages with the assistance of ICG under 808 nm of laser irradiation was obtained. Especially, HAE microlesions at the early stage were detected clearly. Moreover, clear intrahepatic angiography was achieved under the same NIR-II-FMI system.

Opal photonic crystal-enhanced upconversion turn-off fluorescent immunoassay for salivary CEA with oral cancer.

The point-of-care test of tumor markers in saliva with high specificity and sensitivity for early diagnosis of oral cancer is of great interest and significance, but remaining a daunting challenge due to the low concentration of such biomarkers in oral fluid. Herein, a turn-off biosensor based on opal photonic crystal (OPC) enhanced upconversion fluorescence is proposed to detect the carcinoembryonic antigen (CEA) in saliva by applying fluorescence resonance energy transfer sensing strategy. Hydrophilic PEI ligands are modified on upconversion nanoparticles to enhance the sensitivity of biosensor by promoting sufficient contact between saliva and detection region. As a substrate for the biosensor, OPC can also provide a local-field effect for greatly enhanced upconversion fluorescence by coupling the stop band and excitation light, and a 66-fold amplification of the upconversion fluorescence signal was obtained. For the CEA detection in spiked saliva, such sensors showed a favorable linear relationship at 0.1-2.5 ng mL-1 and more than 2.5 ng mL-1, respectively. The limit of detection was down to 0.1 ng mL-1. Moreover, by monitoring real saliva, the effective discrepancy between patients and healthy people was confirmed, indicating remarkable practical application value in clinical early diagnosis and home-based self-monitoring of tumors.

Liposomes loaded with dual clinical photosensitizers for enhanced photodynamic therapy of cervical cancer.

Photodynamic therapy (PDT) has become a potential anti-cancer strategy owing to its negligible invasiveness, low toxicity, and high selectivity. The photosensitizer (PS) plays an indispensable role in PDT. Herein, a novel type of PS (Ce6-MB@Lips) which can be excited by a near-infrared (NIR) laser was designed and synthesized. Methylene blue (MB) and Chlorin e6 (Ce6), two organic dyes approved by the Food and Drug Administration (FDA), were used to prepare Ce6-MB@Lips by thin-film dispersion method, which improve the water solubility of Ce6 and reduce the cytotoxicity of MB. The Ce6-MB@Lips were shown to have a spherical nanostructure with an average particle size of 160.3 nm and excellent water solubility. Then the optical properties of Ce6-MB@Lips were further studied. Ce6-MB@Lips showed absorption peaks at 413 nm/670 nm and fluorescence peak at 697 nm. Compared with Ce6@Lips and MB@Lips, Ce6-MB@Lips showed better stability, stronger fluorescence intensity, and higher singlet oxygen (1O2) generation ability. Cell experimental analysis exhibited that the stable Ce6-MB@Lips showed low cytotoxicity, high phototoxicity and high reactive oxygen species (ROS) production capacity. After effective cell internalization, the prepared Ce6-MB@Lips showed excellent ability to promote tumor cell apoptosis in vitro. The Ce6-MB@Lips could be a promising candidate for PDT of cervical cancer.

PpIX/IR-820 Dual-Modal Therapeutic Agents for Enhanced PDT/PTT Synergistic Therapy in Cervical Cancer.

High treatment accuracy is the key to efficient cancer treatment. Photodynamic therapy (PDT) and photothermal therapy (PTT) are two kinds of popular, precise treatment methods. The combination of photodynamic and photothermal therapy (PDT/PTT) can greatly enhance the precise therapeutic efficacy. In this work, protoporphyrin IX (PpIX) was selected as the PDT agent (photosensitizer), and new indocyanine green (IR-820) was selected as the PTT agent. Further, the two kinds of theranostic agents were encapsulated by biological-membrane-compatible liposomes to form PpIX-IR-820@Lipo nanoparticles (NPs), a new kind of PDT/PTT agent. The PpIX-IR-820@Lipo NPs exhibited good water solubility, a spherical shape, and high fluorescence peak emission in the near-infrared spectral region (700-900 nm, NIR). The cellular toxicity of PpIX-IR-820@Lipo NPs for human cervical cancer cells (HeLa) and human cervical epithelial cells (H8) was detected by the CCK-8 method, and low cytotoxicity was observed for the PpIX-IR-820@Lipo NPs. Then, the excellent cellular uptake of PpIX-IR-820@Lipo NPs was confirmed by laser scanning confocal microscopy. Moreover, the PDT/PTT property of PpIX-IR-820@Lipo NPs was illustrated via 2',7'-dichlorofluorescin diacetate (DCFH-DA) and annexin V-fluorescein isothiocyanate (annexin V-FITC), as indicator probes. The PDT/PTT synergistic efficiency of PpIX-IR-820@Lipo NPs on HeLa cells was verified, exhibiting a high efficiency of 70.5%. Thus, the novel theranostic PpIX-IR-820@Lipo NPs can be used as a promising PDT/PTT synergistic theranostic nanoplatform in future cervical cancer treatment.

Polydopamine encapsulated new indocyanine green theranostic nanoparticles for enhanced photothermal therapy in cervical cancer HeLa cells.

Photothermal therapy (PTT) has attracted extensive attention in cancer treatment due to its non-invasiveness, high efficiency, and repeatability in recent years. Photothermal agents (PTAs) are the key factor for PTT. Recently, although an increasing number of PTAs have been developed, there is still a great demand for optimized photothermal nanoparticles (NPs) with low toxicity, bio-safety and stability. Herein, new indocyanine green (IR820) with near-infrared (NIR:700-1,700 nm) fluorescence emission was selected as a photothermal agent (PTA). To enhance the PTT property, IR820 was encapsulated with another kind of PTA, polydopamine (PDA) under alkaline conditions. Furthermore, to improve the biocompatibility of the NPs, methoxy polyethylene glycol amine (mPEG-NH2) was modified via a Michael addition to form a novel kind of IR820@PDA@PEG NPs. After detailed characterization and analysis, the obtained IR820@PDA@PEG NPs showed a spherical shape with an average diameter of ∼159.6 nm. Meanwhile, the formed IR820@PDA@PEG NPs exhibited better photostability and lower cytotoxicity than free IR820 molecules. The photothermal performance of IR820@PDA@PEG NPs was further analyzed in vitro, and the temperature of IR820@PDA@PEG NPs (100 µg/ml) reached 54.8°C under 793 nm laser irradiation. Afterwards, the cellular uptake of IR820@PDA@PEG NPs was evaluated via confocal laser scanning fluorescence microscopic imaging. Then, PTT experiments on HeLa cells demonstrated that IR820@PDA@PEG NPs can hyperthermal ablate cancer cells (∼49.1%) under 793 nm laser irradiation. Therefore, IR820@PDA@PEG NPs would be a promising PTA for the treatment of cervical cancer HeLa cells.

A highly efficient polydopamine encapsulated clinical ICG theranostic nanoplatform for enhanced photothermal therapy of cervical cancer.

Photothermal therapy (PTT) is a safe and efficient anti-tumor treatment. A photothermal agent (PTA) with good biocompatibility and strong photothermal properties is of great importance for PTT. In this study, near-infrared (NIR) excitable clinical indocyanine green (ICG) was utilized as a PTA and further encapsulated by another PTA polydopamine (PDA) to form highly stable and efficient ICG@PDA nanoparticles (NPs). Then the ICG@PDA NPs were modified with methoxy polyethylene glycol amine (mPEG2000-NH2) to form biocompatible ICG@PDA@PEG NPs. ICG@PDA@PEG NPs showed good water solubility and a spherical shape with an average size of 140 nm. Furthermore, the photothermal properties of ICG@PDA@PEG NPs were studied and excellent photothermal performance with a photothermal conversion efficiency of 43.7% under 808 nm laser irradiation was achieved. Then, the PTT properties of ICG@PDA@PEG NPs were confirmed on HeLa cells with an efficiency of 86.1%. Meanwhile, the in vivo biocompatibility and toxicity of ICG@PDA@PEG NPs were evaluated. No apparent in vivo toxicity was observed in 24 hours and 7 days. Next, in vivo PTT analysis was conducted for cervical tumor-bearing nude mice under 808 nm laser excitation. It showed a good anti-tumor effect in vivo. Thus, ICG@PDA@PEG NPs exhibited great potential for safe and efficient photothermal therapy in anti-tumor therapy.

A novel TMTP1-modified theranostic nanoplatform for targeted in vivo NIR-II fluorescence imaging-guided chemotherapy for cervical cancer.

Near-infrared II (NIR-II, 900-1700 nm) fluorescence bioimaging with advantages of good biosafety, excellent spatial resolution, high sensitivity, and contrast has attracted great attention in biomedical research fields. However, most of the nanoprobes used for NIR-II fluorescence imaging have poor tumor-targeting ability and therapeutic efficiency. To overcome these limitations, a novel NIR-II-emissive theranostic nanoplatform for fluorescence imaging and treatment of cervical cancer was designed and prepared. The NIR-II-emissive dye IR-783 and chemotherapy drug doxorubicin (DOX) were encapsulated into liposomes, and the tumor-targeting peptide TMTP1 (a polypeptide with a sequence of cyclic ASN Val Val Arg Gln Cys) was conjugated to the surface of the liposomes to form IR-783-DOX-TMTP1 nanoparticles (NPs) via self-assembly methods. The IR-783-DOX-TMTP1 NPs showed strong NIR-II emission, excellent biocompatibility and a long lifetime in vivo. Furthermore, high-definition NIR-II fluorescence microscopy images of ear blood vessels and intratumoral blood vessels were obtained from IR-783-DOX-TMTP1 NP-stained mice with high spatial resolution under 808 nm laser excitation. Moreover, IR-783-DOX-TMTP1 NPs showed strong tumor-targeting ability and highly efficient chemotherapeutic characteristics towards cervical tumors. The novel targeting and NIR-II-emissive IR-783-DOX-TMTP1 NPs have great potential in diagnosis and therapy for cervical cancer.

A Class of Biocompatible Dye-Protein Complex Optical Nanoprobes.

Molecular organic dyes are classic fluorescent nanoprobes finding tremendous uses in biological and life sciences. Yet, they suffer from low brightness, poor photostability, and lack of functional groups for bioconjugation. Here, we describe a class of biocompatible dye-protein optical nanoprobes, which show long-time photostability, superbrightness, and enriched functional groups. These nanoprobes utilize apoferritin (an intracellular protein for iron stores and release) to encase appropriate molecular organic dyes to produce on-demand fluorescence in aqueous solution. A pH-driven dissociation-reconstitution process of apoferritin subunits allows substantial incorporation of hydrophilic (aggregation caused quenching, ACQ) or hydrophobic (aggregation induced enhancement, AIE) dye molecules into the protein nanocavity (8 nm), producing monodispersed dye-apoferritin nanoparticles (apo-dye-NPs, ∼12 nm). As compared with single dye monomer, single apo-dye-NPs possess hundreds of times larger molar extinction coefficient and 2 orders of magnitude higher absolute luminescence quantum yield (up to 45-fold), multiplying fluorescence brightness up to 2778-fold. We show that varying the type of incorporated dyes entails a precise control over nanoprobe emission profile tunable in a broad spectral range of 370-1300 nm. Mechanical investigations indicate that the diversified microstructures of nanocavity inner surface are able to conform ACQ dyes at reasonable space interval while providing protein-guided-stacking for AIE dyes, thus enhancing fluorescence quantum yield through confining intermolecular quenching and intramolecular rotation. Moreover, apo-dye-NPs are able to emit stable fluorescence (over 13 min) without quenching in confocal imaging of HepG2 cancer cell under ultrahigh laser irradiance (1.3 × 106 W/cm2). These superb properties make them suitable, as demonstrated in this work, for long-term super-resolved structured illumination microscopic cell imaging (spatial resolution, 117 nm) over 48 h, near-infrared (NIR) fluorescence angiography imaging of whole-body blood vessels (spatial resolution, 380 µm), and NIR photoacoustic imaging of liver in vivo.

[Application of organic fluorescent probe-assisted near infrared fluorescence imaging in cervical cancer diagnosis].

Fluorescence imaging has been widely used in the fields of biomedicine and clinical diagnosis. Compared with traditional fluorescence imaging in the visible spectral region (400-760 nm), near-infrared (NIR, 700-1 700 nm) fluorescence imaging is more helpful to improve the signal-to-noise ratio and the sensitivity of imaging. Highly-sensitive fluorescent probes are required for high-quality fluorescence imaging, and the rapid development of nanotechnology has led to the emergence of organic dyes with excellent fluorescent properties. Among them, organic fluorescent probes with the advantages of high safety, good biocompatibility, and high optical stability, are more favorable than inorganic fluorescent probes. Therefore, NIR fluorescence imaging assisted with organic fluorescent probes can provide more structural and dynamic information of biological samples to the researchers, which becomes a hot spot in the interdisciplinary research field of optics, chemistry and biomedicine. This review summarizes the application of NIR organic fluorescent probes in cervical cancer imaging. Several typical organic fluorescent probes (such as indocyanine green, heptamethine cyanine dye, rhodamine and polymer fluorescent nanoparticles) assisted NIR fluorescence imaging and their applications in cervical cancer diagnosis were introduced, and the future development and application of these techniques were discussed.

Indocyanine Green-Based Theranostic Nanoplatform for NIR Fluorescence Image-Guided Chemo/Photothermal Therapy of Cervical Cancer.

PURPOSE: Indocyanine green (ICG) is a favorable fluorescence nanoprobe for its strong NIR-I fluorescence emission and good photothermal capabilities. However, the stability and tumor targeting ability of ICG is poor, which limits its further applications. To further improve the photothermal and therapeutic efficiency of ICG, bovine serum albumin (BSA) was utilized to encapsulate the ICG and the chemotherapeutic drug doxorubicin (DOX) was loaded to form the BSA@ICG-DOX theranostic nanoplatform. METHODS: In this study, ICG-loaded BSA nanoparticles (NPs) and the BSA@ICG-DOX NPs were fabricated using reprecipitation methods. Next, the tumour inhibition ability and biocompatibility of the NPs were evaluated. A subcutaneous xenografted nude mice model was established and imaging guided synergetic therapy was performed with the assistance of BSA@ICG-DOX NPs under 808 nm laser irradiation. RESULTS: The BSA@ICG NPs exhibited strong NIR-I fluorescence emission, excellent photothermal properties, biocompatibility, and tumor targeting ability. To further improve the therapeutic efficiency, the chemotherapeutic drug doxorubicin (DOX) was loaded into the BSA@ICG NPs to form the BSA@ICG-DOX theranostic nanoplatform. The BSA@ICG-DOX NPs were spherical with an average size of ~194.7 nm. The NPs had high encapsulation efficiency (DOX: 19.96% and ICG: 60.57%), and drug loading content (DOX: 0.95% and ICG: 3.03%). Next, excellent NIR-I fluorescence and low toxicity of the BSA@ICG-DOX NPs were verified. Targeted NIR-I fluorescence images were obtained after intravenous injection of the NPs into the subcutaneous cervical tumors of the mice. CONCLUSION: To improve the anti-tumor efficiency of the ICG@BSA NPs, the chemotherapeutic drug DOX was loaded into the BSA@ICG NPs. The NIR excitation/emission and targeted BSA@ICG-DOX NPs enables high-performance diagnosis and chemo/photothermal therapy of subcutaneous cervical tumors, providing a promising approach for further biomedical applications.

Near-infrared emissive polymer-coated IR-820 nanoparticles assisted photothermal therapy for cervical cancer cells.

Photothermal therapy (PTT) has attracted wide attention due to its noninvasiveness and its thermal ablation ability. As photothermal agents are crucial factor in PTT, those with the characteristics of biocompatibility, non-toxicity and high photothermal stability have attracted great interest. In this work, new indocyanine green (IR-820) was utilized as a photothermal agent and near-infrared (NIR) fluorescence imaging nanoprobe. To improve the biocompatibility, poly(styrene-co-maleic anhydride) (PSMA) was utilized to encapsulate the IR-820 molecules to form novel IR-820@PSMA nanoparticles (NPs). Then, the optical and thermal properties of IR-820@PSMA NPs were studied in detail. The IR-820@PSMA NPs showed excellent photothermal stability and biocompatibility. The cellular uptaking ability of the IR-820@PSMA NPs was further confirmed in HeLa cells by the NIR fluorescent confocal microscopic imaging technique. The IR-820@PSMA NPs assisted PTT of living HeLa cells was conducted under 793 nm laser excitation, and a high PTT efficiency of 73.3% was obtained.

Polymer encapsulated clinical ICG nanoparticles for enhanced photothermal therapy and NIR fluorescence imaging in cervical cancer.

Photothermal therapy (PTT) is a popular tumor therapy method, which is based on efficient photothermal nanoagents (PTNs). Clinical Indocyanine Green (ICG), as a Food and Drug Administration (FDA) approved agent, is an often-used PTN, meanwhile it is also a good near-infrared (NIR) fluorescence contrast agent. However, the further applications of ICG in biomedical fields are limited due to its poor stability. In this study, ICG was encapsulated by the amphiphilic polymer poly(styrene-co-maleic anhydride) (PSMA) to form ICG@PSMA nanoparticles. Furthermore, optical and thermal characteristics of ICG@PSMA nanoparticles were studied in detail. Strong NIR fluorescence and excellent photothermal properties of ICG@PSMA nanoparticles under 808 nm laser irradiation were measured. Besides, favorable biocompatibility of ICG@PSMA nanoparticles was demonstrated on a human cervical cancer cell line (HeLa) via cell viability studies. Hence, ICG@PSMA nanoparticles were further applied to enhanced PTT of living HeLa cells under 808 nm excitation, and a high PTT efficiency of ∼70% was obtained. The novel ICG nanoparticles as a promising PTT nanoplatform could offer an opportunity for further tumour treatments.

Synthesis of an efficient far-red/near-infrared luminogen with AIE characteristics for in vivo bioimaging applications.

A selenium-containing FR/NIR AIE luminogen with efficient solid-state emission is reported. Its AIE dots exhibit high brightness, large Stokes shift, good biocompatibility and satisfactory photostability, making them the first selenium-containing FR/NIR nanoprobes with AIE characteristics for in vivo bioimaging applications with high contrast and a high penetration depth.

Single-Molecular Near-Infrared-II Theranostic Systems: Ultrastable Aggregation-Induced Emission Nanoparticles for Long-Term Tracing and Efficient Photothermal Therapy.

Second near-infrared (NIR-II, 1000-1700 nm) fluorescence bioimaging has attracted tremendous scientific interest and already been used in many biomedical studies. However, reports on organic NIR-II fluorescent probes for in vivo photoinduced imaging and simultaneous therapy, as well as the long-term tracing of specific biological objects, are still very rare. Herein we designed a single-molecular and NIR-II-emissive theranostic system by encapsulating a kind of aggregation-induced emission luminogen (AIEgen, named BPN-BBTD) with amphiphilic polymer. The ultra-stable BPN-BBTD nanoparticles were employed for the NIR-II fluorescence imaging and photothermal therapy of bladder tumors in vivo. The 785 nm excitation triggered photothermal therapy could completely eradicate the subcutaneous tumor and inhibit the growth of orthotopic tumors. Furthermore, BPN-BBTD nanoparticles were capable of monitoring subcutaneous and orthotopic tumors for a long time (32 days). Single-molecular and NIR-II-emitted aggregation-induced emission nanoparticles hold potential for the diagnosis, precise treatment, and metastasis monitoring of tumors in the future.