High-performance PEGylated Mn–Zn ferrite nanocrystals as a passive-targeted agent for magnetically induced cancer theranostics

An effective magnetic nanocrystals (MNCs)-mediated theranostics strategy as a combination of simultaneous diagnostics and heating treatment of tumors by using magnetic resonance imaging (MRI) and alternating current magnetic field (ACMF) is successfully developed. In this strategy, we had firstly synthesized a well-established Mn–Zn ferrite MNCs coated with PEG-phospholipids (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol copolymers, DSPE-PEG2000). The monodisperse PEGylated MNCs with core–shell structure (15 nm) exhibited excellent performance, such as high magnetism of 98 emu g⁻¹ Fe, relaxivity coefficient (r2) of 338 mm⁻¹ s⁻¹, and specific absorption rate (SAR) value of 324 W g⁻¹ Fe. It was proved that the obtained MNCs with an average diameter of 48.6 nm can drastically minimize the recognition and phagocytosis of macrophages, simultaneously improve their biocompatibility in vitro. These advantages endowed them with efficient passive targeting ability in vivo for prominent tumor MRI and magnetically induced heating when exposed to ACMF, based on enhanced permeability and retention (EPR) effects. To ensure sufficient accumulation of MNCs within tumors for targeted hyperthermia, we described the use of MNCs with a well-tolerated intravenous single dose of 18 mg Fe/kg mouse body weight, achieving repeatedly injection and hyperthermia within a subcutaneous breast cell carcinoma mouse model. With an ACMF of 12 A at 390 kHz, the tumor surface sites could be heated to approximately 43 °C in 30 min based on MNCs-mediated intravenous injections. The long-lasting hyperthermia could effectively induce the apoptosis of tumor cells, inhibit the angiogenesis of tumor vessels, and finally suppress the tumor growth within a certain period of time.     

Receptor radionuclide targeting for neuroendocrine tumors (NET) diagnostic and therapy

Neuroendocrine tumors (NET) represent a heterogeneous group of tumors originating from cells of neuroendocrine origin, which express somatostatin receptors (SSTR). This property allowed the successful development of radionuclides for diagnostic and peptide radionuclide radiation therapy (PRRT). This is the paradigm for the theragnostic concept in NET personalized medicine. The only phase III study to date (NETTER-1) clearly demonstrated the ability of ¹⁷⁷Lutetium-based PRRT to improve progression-free survival in advanced intestinal NETs. In clinical practice, the indications are limited to G1-G2 well-differentiated NETs with high expression of SSTR. NETs with a low tumor burden and slow progression are probably the optimal indication. This treatment is now available in France. However, its precise position in the treatment algorithm remains to be explored. We provide an overview of receptor radionuclide utilization and mechanism in diagnostic and pretherapeutic imaging and we focus on PRRT for endocrine tumors.     

磁性纳米颗粒在癌症诊疗一体化中的应用进展

癌症是21世纪威胁人类健康的三大杀手之一,目前比较有前景的研究方向是关于癌症的早期诊断和高效低毒的治疗方案,纳米技术的兴起给此方面研究带来了新的希望.其中,磁性纳米颗粒由于可以在固定磁场中定位,且具有可在交变磁场振动发热的特性,因此在诊疗一体化方面有显著的效果.随着对磁性纳米颗粒的深入研究,磁性纳米颗粒也必然在癌症治疗方面展现出独特能力.综述了单金属、双金属以及合金纳米颗粒在癌症诊疗一体化中的主要应用及进展,并对磁性纳米技术的应用前景进行了展望.磁性纳米颗粒目前已经得到了较为广泛的应用,而且无论是理论研究还是应用研究都发展得很快,但在磁性纳米颗粒被确认为低毒有效、诊疗俱备之前,磁性纳米颗粒对细胞、组织与器官的毒性、商用及医用标准化等问题还有待继续深入研究.     

Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery

Previous attempts to review the literature on magnetic nanomaterials for hyperthermia-based therapy focused primarily on magnetic fluid hyperthermia (MFH) using mono metallic/metal oxide nanoparticles. The term “hyperthermia” in the literature was also confined only to include use of heat for therapeutic applications. Recently, there have been a number of publications demonstrating magnetic nanoparticle-based hyperthermia to generate local heat resulting in the release of drugs either bound to the magnetic nanoparticle or encapsulated within polymeric matrices. In this review article, we present a case for broadening the meaning of the term “hyperthermia” by including thermotherapy as well as magnetically modulated controlled drug delivery. We provide a classification for controlled drug delivery using hyperthermia: Hyperthermia-based controlled drug delivery through bond breaking (DBB) and hyperthermia-based controlled drug delivery through enhanced permeability (DEP). The review also covers, for the first time, core-shell type magnetic nanomaterials, especially nanoshells prepared using layer-by-layer self-assembly, for the application of hyperthermia-based therapy and controlled drug delivery. The highlight of the review article is to portray potential opportunities for the combination of hyperthermia-based therapy and controlled drug release paradigms -towards successful application in personalized medicine.     

SPECT/CT imaging of radiolabeled cubosomes and hexosomes for potential theranostic applications

We have developed a highly efficient method for the radiolabeling of phytantriol (PHYT)/oleic acid (OA)-based hexosomes based on the surface chelation of technetium-99m (^99mTc) to preformed hexosomes using the polyamine 1, 12-diamino-3, 6, 9-triazododecane (SpmTrien) as chelating agent. We also report on the unsuccessful labeling of cubosomes using the well-known chelating agent hexamethylpropyleneamine oxime (HMPAO). The ^99mTc-labeled SpmTrien-hexosomes (^99mTc-SpmTrien-hexosomes) were synthesized with good radiolabeling (84%) and high radiochemical purity (>90%). The effect of radiolabeling on the internal nanostructure and the overall size of these aqueous dispersions was investigated by using synchrotron small angle X-ray scattering (SAXS), dynamic light scattering (DLS), and transmission electron cryo microscopy (cryo-TEM). Further, we show the utility of ^99mTc-SpmTrien-hexosomes for the in vivo imaging of healthy mice using single photon emission computed tomography (SPECT) in combination with computed tomography (CT), i.e. SPECT/CT. SPECT/CT experiments of subcutaneously administered ^99mTc-SpmTrien-hexosomes to the flank of mice showed a high stability in vivo allowing imaging of the distribution of the radiolabeled hexosomes for up to 24 h. These injected ^99mTc-SpmTrien-hexosomes formed a deposit within the subcutaneous adipose tissue, displaying a high biodistribution of ∼343% injected dose/g tissue (%ID/g), with negligible uptake in other organs and tissues. The developed ^99mTc labeling method for PHYT/OA-based hexosomes could further serve as a useful tool for investigating and imaging the in vivo performance of cubosomal and hexosomal drug nanocarriers.     

Angiogenesis-Targeted 68Ga-DOTA-RGD2 PET/CT Imaging: a Potential Theranostic Application in the Case of Chondrosarcoma

Chondrosarcoma is a cartilaginous tumor of mesenchymal origin. The histology and grade of the tumor determine the chances of relapse and survival. These tumors usually respond poorly to chemo-radiotherapy in cases of non-resectable and recurrent disease. ¹⁸F-FDG PET/CT has been used in evaluation of recurrence. However, these tumors show only mild to moderate FDG avidity due to their lower mitotic activity and large acellular matrix. These tumors are known to have a high degree of angiogenesis, especially in those of higher grade. We present a case of a 53-year-old man with grade II chondrosarcoma of the left femur showing only mild avidity on ¹⁸F-FDG PET/CT but showing moderate to intense tracer avidity on ⁶⁸Ga-DOTA-RGD₂ PET/CT. This may enable the use of angiogenesis-targeted positron and beta-emitting radiopharmaceuticals as a potentially new theranostic alternative treatment in cases of refractory metastatic chondrosarcoma.     

The analytical and biomedical applications of carbon dots and their future theranostic potential: A review

In recent years, carbon dots (C-dots) have gained appreciable interest owing to their unique optical properties, including tunable fluorescence, stability against photobleaching and photoblinking, and strong fluorescence. Simple and low-cost hydrothermal and electrochemical approaches have been widely used in the preparation of biocompatible and high-quality C-dots. Various C-dots have been used for the quantitation of small analytes, mostly based on analyte induced fluorescence quenching. Depending on the nature of precursors, synthetic conditions (such as reaction temperature and time), and surface conjugation, multi-function C-dots can be prepared and used in diagnostics and therapeutics. Their strong fluorescence and photostability, enables use in cell imaging. Their biological activity from the surface residues and capability of generating reactive oxygen species, have allowed many C-dots to become candidates as antibacterial and anticancer reagents. After suitable conjugation, biocompatible and fluorescent C-dots can be used for diagnostics and therapeutics, thus, showing their great potential in the area of theranostics.     

Magnetism in drug delivery: The marvels of iron oxides and substituted ferrites nanoparticles

In modern drug delivery, seeking a drug delivery system (DDS) with a modifiable skeleton for proper targeting of loaded actives to specific sites in the body is of extreme importance for a successful therapy. Magnetically guided nanosystems, where particles such as iron oxides are guided to specific regions using an external magnetic field, can provide magnetic resonance imaging (MRI) while delivering a therapeutic payload at the same time, which represents a breakthrough in disease therapy and make MNPs excellent candidates for several biomedical applications. In this review, magnetic nanoparticles (MNPs) along with their distinguishable properties, including pharmacokinetics and toxicity, especially in cancer therapy will be discussed. The potential perspective of using other elements within the MNP system to reduce toxicity, improve pharmacokinetics, increase the magnetization ability, improve physical targeting precision and/or widen the scope of its biomedical application will be also discussed.