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![Preparation of doxorubicin (DOX)-loaded silk films. (A) Techniques to synthesize DOXloaded films that are water-soluble or (B) water-insoluble with variable beta-sheet content. (C) Film thickness of dry and hydrated silk films. (D) Doxorubicin-loaded silk films in the dry state (scale bar, 7 mm). (E) Hydrated films following surface contours (scale bar, 7 mm). (F) Various concentration ranges of DOX loaded in silk films. Reprinted with permission from ref. [58]. Copyright 2012 Elseveir.](publication/358498929/figure/fig3/AS:1141010973372416@1649049623209/Preparation-of-doxorubicin-DOX-loaded-silk-films-A-Techniques-to-synthesize.png)
Preparation of doxorubicin (DOX)-loaded silk films. (A) Techniques to synthesize DOXloaded films that are water-soluble or (B) water-insoluble with variable beta-sheet content. (C) Film thickness of dry and hydrated silk films. (D) Doxorubicin-loaded silk films in the dry state (scale bar, 7 mm). (E) Hydrated films following surface contours (scale bar, 7 mm). (F) Various concentration ranges of DOX loaded in silk films. Reprinted with permission from ref. [58]. Copyright 2012 Elseveir.
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Breast cancer is one of the leading causes of death in the female population worldwide. Standard treatments such as chemotherapy show noticeable results. However, along with killing cancer cells, it causes systemic toxicity and apoptosis of the nearby healthy cells, therefore patients must endure side effects during the treatment process. Implantab...
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Context 1
... degradation rate and biocompatibility make silk an excellent drug carrier. Seib et al. applied DOX-loaded silk films having different crystallinity contents or beta-sheets (Figure 3) which were fabricated using water vapor annealing for breast cancer treatment [58]. The adenocarcinoma breast cancer cell line MDA-MB-231 was used for the experiment here and maintained in a humidified atmosphere of 5% CO 2 at 37 • C and was routinely subcultured every 2-3 days. ...
Citations
... Implants allow for localized drug delivery, enabling targeted and sustained release of therapeutic agents directly into the tumor microenvironment (53). This localized drug delivery minimizes systemic exposure and reduces potential side effects, enhancing the overall safety profile of the treatment (54). Moreover, implants can overcome limitations associated with poor drug penetration and distribution within solid tumors, ensuring more efficient drug delivery to cancerous cells. ...
Introduction: Computational models yield valuable insights into biological interactions not fully elucidated by experimental approaches. This study investigates an innovative spatiotemporal model for simulating the controlled release and dispersion of radiopharmaceutical therapy (RPT) using 177Lu-PSMA, a prostate-specific membrane antigen (PSMA) targeted radiopharmaceutical, within solid tumors via a dual-release implantable delivery system. Local delivery of anticancer agents presents a strategic approach to mitigate adverse effects while optimizing therapeutic outcomes.
Methods: This study evaluates various factors impacting RPT efficacy, including hypoxia region extension, binding affinity, and initial drug dosage, employing a novel 3-dimensional computational model. Analysis gauges the influence of these factors on radiopharmaceutical agent concentration within the tumor microenvironment. Furthermore, spatial and temporal radiopharmaceutical distribution within both the tumor and surrounding tissue is explored.
Results: Analysis indicates a significantly higher total concentration area under the curve within the tumor region compared to surrounding normal tissue. Moreover, drug distribution exhibits notably superior efficacy compared to the radiation source. Additionally, low microvascular density in extended hypoxia regions enhances drug availability, facilitating improved binding to PSMA receptors and enhancing therapeutic effectiveness. Reductions in the dissociation constant (KD) lead to heightened binding affinity and increased internalized drug concentration. Evaluation of initial radioactivities (7.1×107, 7.1×108, and 7.1×109 [Bq]) indicates that an activity of 7.1×108 [Bq] offers a favorable balance between tumor cell elimination and minimal impact on normal tissues.
Discussion: These findings underscore the potential of localized radiopharmaceutical delivery strategies and emphasize the crucial role of released drugs relative to the radiation source (implant) in effective tumor treatment. Decreasing the proximity of the drug to the microvascular network and enhancing its distribution within the tumor promote a more effective therapeutic outcome. The study furnishes valuable insights for future experimental investigations and clinical trials, aiming to refine medication protocols and minimize reliance on in vivo testing.
... These are efficacious because they allow for better local drug concentration with minimal systemic side effects, more so than nanoparticles, and allow for controlled temporal sustained release. The type of drug depot, either a monolithic matrix or a reservoir implant design, is chosen based on the drug kinetics [71]. Zero-order drugs are implanted with a reservoir implant, while first-order kinetics are paired with a matrix implant. ...
Simple Summary
Interventional radiology is a highly evolving field that can modulate the various barriers imposed by the immunosuppressive tumor microenvironment. This review aims to showcase the various immune biophysical barriers that limit anti-cancer therapy by the tumor microenvironment and how interventional radiology possesses the facilities to overcome these barriers. These tools involve both physical and immune therapies that can be intratumorally injected to act locally but recruit a systemic response to produce a more potentiated anti-cancer therapeutic response.
Abstract
The tumor microenvironment (TME) is a unique landscape that poses several physical, biochemical, and immune barriers to anti-cancer therapies. The rapidly evolving field of immuno-engineering provides new opportunities to dismantle the tumor immune microenvironment by efficient tumor destruction. Systemic delivery of such treatments can often have limited local effects, leading to unwanted offsite effects such as systemic toxicity and tumor resistance. Interventional radiologists use contemporary image-guided techniques to locally deliver these therapies to modulate the immunosuppressive TME, further accelerating tumor death and invoking a better anti-tumor response. These involve local therapies such as intratumoral drug delivery, nanorobots, nanoparticles, and implantable microdevices. Physical therapies such as photodynamic therapy, electroporation, hyperthermia, hypothermia, ultrasound therapy, histotripsy, and radiotherapy are also available for local tumor destruction. While the interventional radiologist can only locally manipulate the TME, there are systemic offsite recruitments of the immune response. This is known as the abscopal effect, which leads to more significant anti-tumoral downstream effects. Local delivery of modern immunoengineering methods such as locoregional CAR-T therapy combined with immune checkpoint inhibitors efficaciously modulates the immunosuppressive TME. This review highlights the various advances and technologies available now to change the TME and revolutionize oncology from a minimally invasive viewpoint.
Breast cancer is the most frequently detected malignancy in females worldwide. The early-stage and non-invasive type BC patients undergo breast-conserving surgery and radiotherapy. Whereas, advanced-stage BC patients are treated systemically via chemotherapy, immunotherapy, hormonal therapy, and nano-targeted therapy. However, local-regional recurrence and systemic side effects are common problems associated with these approaches. In the past two decades nanofibers (NF) assisted local delivery of anti-cancer drugs has shown potential for the treatment of BC over other systemically administered colloidal-based drug delivery approaches. NF have multiple advantages including localized sustained delivery at the tumor site, higher encapsulation efficiency, enhanced surface area-to-volume ratio, solubility, stability, easy scale-up, and minimal systemic side effects. In addition, the NF loaded with anti-cancer drugs can be implanted in the cavity created after mastectomy or breast-conserving surgery to kill the residual BC cells and reduce the chances of local-regional recurrence. Electrospinning is the most common method among all explored for NF fabrication due to its facile, cost-effective, versatile, and efficient functioning. In recent years different electrospun NF like blended, co-axial, composite, and stimuli-responsive have been explored for local delivery of anti-cancer drugs. Therefore, the major focus of this review is to critically analyze different electrospinning approaches used for NF fabrication along with their merits and demerits. Moreover, applications of electrospun NF (blend, co-axial, composite, hybrid and stimuli responsive) in local delivery of small molecule drugs, bioactives, gene and protein-based drugs for BC treatment have been presented in this paper.
Machine learning and digital health sensing data have led to numerous research achievements aimed at improving digital health technology. However, using machine learning in digital health poses challenges related to data availability, such as incomplete, unstructured, and fragmented data, as well as issues related to data privacy, security, and data format standardization. Furthermore, there is a risk of bias and discrimination in machine learning models. Thus, developing an accurate prediction model from scratch can be an expensive and complicated task that often requires extensive experiments and complex computations. Transfer learning methods have emerged as a feasible solution to address these issues by transferring knowledge from a previously trained task to develop high-performance prediction models for a new task. This survey paper provides a comprehensive study of the effectiveness of transfer learning for digital health applications to enhance the accuracy and efficiency of diagnoses and prognoses, as well as to improve healthcare services. The first part of this survey paper presents and discusses the most common digital health sensing technologies as valuable data resources for machine learning applications, including transfer learning. The second part discusses the meaning of transfer learning, clarifying the categories and types of knowledge transfer. It also explains transfer learning methods and strategies, and their role in addressing the challenges in developing accurate machine learning models, specifically on digital health sensing data. These methods include feature extraction, fine-tuning, domain adaptation, multitask learning, federated learning, and few-/single-/zero-shot learning. This survey paper highlights the key features of each transfer learning method and strategy, and discusses the limitations and challenges of using transfer learning for digital health applications. Overall, this paper is a comprehensive survey of transfer learning methods on digital health sensing data which aims to inspire researchers to gain knowledge of transfer learning approaches and their applications in digital health, enhance the current transfer learning approaches in digital health, develop new transfer learning strategies to overcome the current limitations, and apply them to a variety of digital health technologies.
Metastasis is a leading cause of mortality in cancer patients. The journey of a detached primary tumour cell to a secondary homing site is a multi-step process with several intercellular interactions. In this process, a metastatic cell overcomes many barriers and adapts to the changing microenvironment. Our understanding of motility, invasion and epithelial to mesenchymal transition has led to the identification of targetable signalling networks and regulatory pathways. Emerging research has also identified genetic heterogeneity and variable microenvironment in the primary tumour cell as different from its metastatic progeny, leading to differential immune response. Therapeutic regimes with both standard chemotherapy and, in some cases, targeted therapy have only marginally improved the overall survival in metastatic cancer patients. It is for this reason that the current research strives to understand metastatic cancer, its origin and the role of the tumour microenvironment in genesis and persistence of metastasis. The hypoxic tumour microenvironment is known to arise in such growing primary tumours, where the vasculature is unable to keep pace with the high rate of proliferation, forming hypoxic niche within the tumours. Hypoxia, therefore, will always precede metastasis, thus implicating that the former plays a larger role in the development of the aggressive phenotype. Some of the leading research of our times is trying to understand latency of cancer cells, immune-metastatic cell interaction and epigenetic changes that promote metastasis and chemoresistance. With exciting possibilities of immunotherapeutic and other intervention strategies, a comprehensive understanding of the role of hypoxia in promoting metastasis will be useful. In this review, we dissect how hypoxia, hypoxia-inducible factors and other associated molecules dynamically modulate various stages of metastasis.KeywordsHypoxiaMetastasisHIFInvasionTumour-microenvironmentEMTSignallingImmune evasionEpigeneticsAnti-cancer therapyChemoresistanceCTCs
