Herein, we report a novel therapy for prostate cancer based on systemically delivered magnetic hyperthermia. Conventional magnetic hyperthermia is a form of thermal therapy where magnetic nanoparticles delivered to cancer sites via intratumoral administration produce heat in the presence of an alternating magnetic field (AMF). To employ this therapy for prostate cancer tumors that are challenging to inject intratumorally, we designed novel nanoclusters with enhanced heating efficiency that reach prostate cancer tumors after systemic administration and generate desirable intratumoral temperatures upon exposure to an AMF. Our nanoclusters are based on hydrophobic iron oxide nanoparticles doped with zinc and manganese. To overcome the challenges associated with the poor water solubility of the synthesized nanoparticles, the solvent evaporation approach was employed to encapsulate and cluster them within the hydrophobic core of PEG-PCL (methoxy poly(ethylene glycol)-b-poly(ε-caprolactone))-based polymeric nanoparticles. Animal studies demonstrated that, following intravenous injection into mice bearing prostate cancer grafts, the nanoclusters efficiently accumulated in cancer tumors within several hours and increased the intratumoral temperature above 42 °C upon exposure to an AMF. Finally, the systemically delivered magnetic hyperthermia significantly inhibited prostate cancer growth and did not exhibit any signs of toxicity.

Endometriosis is an incurable gynecological disease characterized by the abnormal growth of endometrium‐like tissue, characteristic of the uterine lining, outside of the uterine cavity. Millions of people with endometriosis suffer from pelvic pain and infertility. This review aims to discuss whether nanomedicines that are promising therapeutic approaches for various diseases have the potential to create a paradigm shift in endometriosis management. For the first time, the available reports and achievements in the field of endometriosis nanomedicine are critically evaluated, and a summary of how nanoparticle‐based systems can improve endometriosis treatment and diagnosis is provided. Parallels between cancer and endometriosis are also drawn to understand whether some fundamental principles of the well‐established cancer nanomedicine field can be adopted for the development of novel nanoparticle‐based strategies for endometriosis. This review provides the state of the art of endometriosis nanomedicine and perspective for researchers aiming to realize and exploit the full potential of nanoparticles for treatment and imaging of the disorder.

Endometriosis is a devastating disease in which endometrial‐like tissue forms lesions outside the uterus. It causes infertility and severe pelvic pain in ≈176 million women worldwide, and there is currently no cure for this disease. Magnetic hyperthermia could potentially eliminate widespread endometriotic lesions but has not previously been considered for treatment because conventional magnetic nanoparticles have relatively low heating efficiency and can only provide ablation temperatures (>46 °C) following direct intralesional injection. This study is the first to describe nanoparticles that enable systemically delivered magnetic hyperthermia for endometriosis treatment. When subjected to an alternating magnetic field (AMF), these hexagonal iron‐oxide nanoparticles exhibit extraordinary heating efficiency that is 6.4× greater than their spherical counterparts. Modifying nanoparticles with a peptide targeted to vascular endothelial growth factor receptor 2 (VEGFR‐2) enhances their endometriosis specificity. Studies in mice bearing transplants of macaque endometriotic tissue reveal that, following intravenous injection at a low dose (3 mg per kg), these nanoparticles efficiently accumulate in endometriotic lesions, selectively elevate intralesional temperature above 50 °C upon exposure to external AMF, and completely eradicate them with a single treatment. These nanoparticles also demonstrate promising potential as magnetic resonance imaging (MRI) contrast agents for precise detection of endometriotic tissue before AMF application.

Pseudo-oligosaccharides are microbial-derived secondary metabolites whose chemical structures contain pseudosugars (glycomimetics). Due to their high resemblance to the molecules of life (carbohydrates), most pseudo-oligosaccharides show significant biological activities. Some of them have been used as drugs to treat human and plant diseases. Because of their significant economic value, efforts have been put into understanding their biosynthesis, optimizing their fermentation conditions, and engineering their metabolic pathways to obtain better production yields. A number of unusual enzymes participating in diverse biosynthetic pathways to pseudo-oligosaccharides have been reported. Various methods and conditions to improve the production yields of the target compounds and eliminate byproducts have also been developed. This review article describes recent studies on the biosynthesis, fermentation optimization, and metabolic engineering of high-value pseudo-oligosaccharides.

Due to the limited heating efficiency of available magnetic nanoparticles, it is difficult to achieve therapeutic temperatures above 44 °C in relatively inaccessible tumors during magnetic hyperthermia following systemic administration of nanoparticles at clinical dosage (≤10 mg kg−1). To address this, a method for the preparation of magnetic nanoparticles with ultrahigh heating capacity in the presence of an alternating magnetic field (AMF) is presented. The low nitrogen flow rate of 10 mL min−1 during the thermal decomposition reaction results in cobalt‐doped nanoparticles with a magnetite (Fe3O4) core and a maghemite (γ‐Fe2O3) shell that exhibit the highest intrinsic loss power reported to date of 47.5 nH m2 kg−1. The heating efficiency of these nanoparticles correlates positively with increasing shell thickness, which can be controlled by the flow rate of nitrogen. Intravenous injection of nanoparticles at a low dose of 4 mg kg−1 elevates intratumoral temperatures to 50 °C in mice‐bearing subcutaneous and metastatic cancer grafts during exposure to AMF. This approach can also be applied to the synthesis of other metal‐doped nanoparticles with core–shell structures. Consequently, this method can potentially be used for the development of novel nanoparticles with high heating performance, further advancing systemic magnetic hyperthermia for cancer treatment.

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Recently, therapeutics based on mRNA (mRNA) have attracted significant interest for vaccines, cancer immunotherapy, and gene editing. However, the lack of biocompatible vehicles capable of delivering mRNA to the target tissue and efficiently expressing the encoded proteins impedes the development of mRNA-based therapies for a variety of diseases. Herein, we report mRNA-loaded polymeric nanoparticles based on diethylenetriamine-substituted poly­(aspartic acid) that induce protein expression in the lungs and muscles following intravenous and intramuscular injections, respectively. Animal studies revealed that the amount of polyethylene glycol (PEG) on the nanoparticle surface affects the translation of the delivered mRNA into the encoded protein in the target tissue. After systemic administration, only mRNA-loaded nanoparticles modified with PEG at a molar ratio of 1:1 (PEG/polymer) induce protein expression in the lungs. In contrast, protein expression was detected only following intramuscular injection of mRNA-loaded nanoparticles with a PEG/polymer ratio of 10:1. These findings suggest that the PEG density on the surface of poly­(aspartic acid)-based nanoparticles should be optimized for different delivery routes depending on the purpose of the mRNA treatment.

Ectopic pregnancy (EP) is the leading cause of maternity‐related death in the first trimester of pregnancy. Approximately 98% of ectopic implantations occur in the fallopian tube, and expedient management is crucial for preventing hemorrhage and maternal death in the event of tubal rupture. Current ultrasound strategies misdiagnose EP in up to 40% of cases, and the failure rate of methotrexate treatment for confirmed EP exceeds 10%. Here the first theranostic strategy for potential management of EP is reported using a near‐infrared naphthalocyanine dye encapsulated within polymeric nanoparticles. These nanoparticles preferentially accumulate in the developing murine placenta within 24 h following systemic administration, and enable visualization of implantation sites at various gestational stages via fluorescence and photoacoustic imaging. These nanoparticles do not traverse the placental barrier to the fetus or impact fetal development. However, excitation of nanoparticles localized in specific placentas with focused NIR light generates heat (>43 °C) sufficient for disruption of placental function, resulting in the demise of targeted fetuses with no effect on adjacent fetuses. This novel approach would enable diagnostic confirmation of EP when current imaging strategies are unsuccessful, and elimination of EP could subsequently be achieved using the same nano‐agent to generate localized hyperthermia resulting in targeted placental impairment.