Self-propelling bacteria-based magnetic nanoparticles (BacMags) for targeted magnetic hyperthermia therapy against hypoxic tumors.

Magnetic hyperthermia-based cancer therapy (MHCT) holds great promise as a non-invasive approach utilizing heat generated by an alternating magnetic field for effective cancer treatment. For an efficacious therapeutic response, it is crucial to deliver therapeutic agents selectively at the depth of tumors. In this study, we present a new strategy using the naturally occurring tumor-colonizing bacteria Escherichia coli (E. coli) as a carrier to deliver magnetic nanoparticles to hypoxic tumor cores for effective MHCT. Self-propelling delivery agents, "nano-bacteriomagnets" (BacMags), were developed by incorporating anisotropic magnetic nanocubes into E. coli which demonstrated significantly improved hyperthermic performance, leading to an impressive 85% cell death in pancreatic cancer. The in vivo anti-cancer response was validated in a syngeneic xenograft model with a 50% tumor inhibition rate within 20 days and a complete tumor regression within 30 days. This proof-of-concept study demonstrates the potential of utilizing anaerobic bacteria for the delivery of magnetic nanocarriers as a smart therapeutic approach for enhanced MHCT.

Fundamentals of utilizing microbes in advanced cancer therapeutics: current understanding and potential applications.

One of the biggest health related issues in the twenty-first century is cancer. The current therapeutic platforms have not advanced enough to keep up with the number of rising cases. The traditional therapeutic approaches frequently fail to produce the desired outcomes. Therefore, developing new and more potent remedies is crucial. Recently, investigating microorganisms as potential anti-cancer treatments have garnered a lot of attention. Tumor-targeting microorganisms are more versatile at inhibiting cancer than the majority of standard therapies. Bacteria preferentially gather and thrive inside tumors, where they can trigger anti-cancer immune responses. They can be further trained to generate and distribute anticancer drugs based on clinical requirements using straightforward genetic engineering approaches. To improve clinical outcomes, therapeutic strategies utilizing live tumor-targeting bacteria can be used either alone or in combination with existing anticancer treatments. On the other hand, oncolytic viruses that target cancer cells, gene therapy via viral vectors, and viral immunotherapy are other popular areas of biotechnological investigation. Therefore, viruses serve as a unique candidate for anti-tumor therapy. This chapter describes the role of microbes, primarily bacteria and viruses in anti-cancer therapeutics. The various approaches to utilizing microbes in cancer therapy are discussed and examples of microorganisms that are now in use or that are undergoing experimental research are briefly discussed. We further point out the hurdles and the prospects of microbes-based remedies for cancer treatment.

Nickel Complexes Bearing ONS Chelating Ligands: A Promising Contender for In Vitro Cytotoxicity Effects on Human Pancreatic Cancer MIA-PaCa-2 Cells.

The highly chronic human pancreatic cancer cell is one of the major reasons for cancerous death. Nickel complexes are recently gaining interest in anticancer activities on different types of cancer cells. Hence, in this study, we synthesized and characterized a series of ONS donor ligands [2-HO-C6H4-CH═N-(C6H4)-SH] (L1), [2-OH-3-OMe-C6H3-CH═N-(C6H4)-SH] (L2), [2-OH-3,5-(C(Me)3)2-C6H2-CH═N-(C6H4)-SH] (L3), [2-OH-C6H4-CH═N-(C6H4)-SMe] (L4), [2-OH-3-OMe-C6H3-CH═N-(C6H4)-SMe] (L5), [2-OH-3,5-(C(Me)3)2-C6H2-CH═N-(C6H4)-SMe] (L6) and their Ni(II) metal complexes [(MeOH)Ni(L1-L1-4H)] (1), [(MeOH)Ni(L2-L2-4H)] (2), [(MeOH)Ni(L3-L3-4H)] (3), [(L4-H)2Ni] (4), [(L5-H)2Ni] (5), and [(L6-H)2Ni] (6). The single-crystal X-ray diffraction data of complexes 1 and 4 were collected to elucidate the geometry around the metal center. The anticancer activity of complexes 1-6 was investigated on human pancreatic cancer cell line MIA-PaCa-2, which revealed that complexes 4 and 6 were the most significantly effective in decreasing the cell viability of cancer cells at the lowest dose. The structure parameters obtained from single-crystal X-ray diffraction data are found to be in good agreement with the data from density functional theory and Hirshfeld surface analysis for complex 1.

Transmigration of magnetite nanoparticles across the blood-brain barrier in a rodent model: influence of external and alternating magnetic fields.

Despite advances in neurology, drug delivery to the central nervous system is considered a challenge due to the presence of the blood brain barrier (BBB). In this study, the role of magnetic hyperthermia induced by exposure of magnetic nanoparticles (MNPs) to an alternating magnetic field (AMF) in synergy with an external magnetic field (EMF) was investigated to transiently increase the permeability of the MNPs across the BBB. A dual magnetic targeting approach was employed by first dragging the MNPs by an EMF for an intended enhanced cellular association with the brain endothelial cells and then activating the MNPs by an AMF for the temporary disruption of the tight junctions of BBB. The efficacy of the BBB permeability for the MNPs under the influence of dual magnetic targeting was evaluated in vitro using transwell models developed by co-culturing murine brain endothelial cells with astrocytes, as well as in vivo in mouse models. The in vitro results revealed that the exposure to AMF transiently opened the tight junctions at the BBB, which, after 3 h of treatment, were observed to recover back to their comparable control levels. A biodistribution analysis of nanoparticles confirmed targeted accumulation of MNPs in the brain following dual targeting. This dual targeting approach was observed to open the tight junctions, thus increasing the transport of MNPs into the brain with higher specificity as compared to using EMF targeting alone, suggesting that a dual magnetic targeting-induced transport of MNPs across the BBB is an effective measure for delivery of therapeutics.

Expansion of thermometry in magnetic hyperthermia cancer therapy: antecedence and aftermath.

Magnetic hyperthermia cancer therapy (MHCT) is a promising antitumor therapy based on the generation of heat by magnetic nanoparticles under the influence of an alternating-current magnetic field. However, an often-overlooked factor hindering the translation of MHCT to clinics is the inability to accurately monitor temperature, thereby leading to erroneous thermal control. It is significant to address 'thermometry' during magnetic hyperthermia because numerous factors are affected by the magnetic fields employed, rendering traditional thermometry methods unsuitable for temperature estimation. Currently, there is a dearth of literature describing appropriate techniques for thermometry during MHCT. This review offers a general outline of the various modes of conventional thermometry as well as cutting-edge techniques operating at cellular/nanoscale levels (nanothermometry) as prospective thermometers for MHCT in the future.

Tailoring nanoparticles design for enhanced heating efficiency and improved magneto-chemo therapy for glioblastoma.

Development of multifunctional magnetic nanomaterials (MNPs) with improved heat-generating capabilities and effective combination with localized chemotherapy has emerged as a promising therapeutic regime for solid tumors like glioblastoma. In this regard, the shape-dependent hyperthermic and chemo-therapeutic potential of nanomaterials, has not been extensively explored. Here we present, development of various morphological designs of MNPs including spherical, clusters, rods and cubic; to compare the effect of shape on tuning the properties of MNPs that are relevant to many potential biomedical applications like drug delivery, cellular uptake and heat generation. The study includes extensive comparison of morpho-structural characteristics, size distributions, chemical composition, surface area measurements and magnetic properties of the variable shaped MNPs. Further the heating efficiencies in aqueous and cellular environments and heat triggered drug release profiles for successful magneto-chemotherapy were compared among all in-house synthesized MNPs. Under biosafety limit considerations given by Hergt's limit (H*f value <5 × 109 Am-1 s-1), cuboidal shaped MNPs demonstrated highest heating efficiency owing to magnetosome-like chain formation along with sustained drug release profile as compared to other synthesized MNPs. The mechanism of cancer cell death mediated via magneto-chemotherapy was elucidated to be the oxidative stress-mediated apoptotic cell death pathway. In vivo studies further demonstrated complete tumor regression only in the magneto-chemotherapy treated group. These findings suggest the potential of combinatorial therapy to overcome the clinical limitations of the independent therapies for advanced thermotherapy of glioblastoma.