Cancer Drug Delivery Research Articles

Internet of Bio-NanoThings privacy: securing a multi compartmental targeted cancer drug delivery scheme

The Internet of Bio-Nano Things concept (IoBNT) emerged from the need to establish connections between biological nanomachines, the intra-body nanonetwork, and the cyber internet to facilitate information exchange. While extensive research has concentrated on optimizing communication efficiency among nanodevices within networks, challenges such as IoBNT security and the interface linking nanonetwork to the internet have remained unaddressed. Consequently, this study introduces a privacy scheme designed to operate atop the Physical Cyber Interface (pHCI) within the IoBNT framework. Our proposed chaotic system derives its foundation from the command signals issued by medical personnel to pHCI devices implanted within the human body. It employs a concealed version of features generated through a Modified Quadratic Map (MQM) to enhance the privacy of patient information and to ensure a precise dosage release. Additionally, our scheme incorporates Binary Phase Shifting Key (BPSK) modulation through the incorporation of a carrier wave, along with feature extraction with zero-crossing rates. This privacy scheme significantly amplifies the key space, thereby guaranteeing an accurate right dose release with the protection of patient privacy. To assess the performance of our proposed scheme, we evaluate its operation on top of the pHCI device using various performance metrics. Subsequently, we study its performance by employing multi-compartmental models in both the forward and reverse pHCI directions of the IoBNT paradigm. The results from our simulation model clearly illustrate that the IoBNT-based privacy scheme has potential to enhance the delivery of therapeutic drugs to target cells while effectively addressing privacy concerns. An evaluation of performance metrics for two binary codes (thermal and light) reveals sensitivity and specificity rates of 95.333% and 95%, 100%, and 100%, respectively. Furthermore, the performance of our proposed privacy scheme, as measured by EER, accuracy, NPV, and PPV, has proven to be highly satisfactory. Hence, our proposed scheme makes significant role in enhancing the security of the physical cyber interface device while remaining cost-effective, and ensuring the safety of patients' life and confidentiality.

Revolutionizing Cancer Treatment: The Promising Horizon of Zein Nanosystems.

Various nanomaterials have recently become fascinating tools in cancer diagnostic applications because of their multifunctional and inherent molecular characteristics that support efficient diagnosis and image-guided therapy. Zein nanoparticles are a protein derived from maize. It belongs to the class of prolamins possessing a spherical structure with conformational properties similar to those of conventional globular proteins like ribonuclease and insulin. Zein nanoparticles have gained massive interest over the past couple of years owing to their natural hydrophilicity, ease of functionalization, biodegradability, and biocompatibility, thereby improving oral bioavailability, nanoparticle targeting, and prolonged drug administration. Thus, zein nanoparticles are becoming a promising candidate for precision cancer drug delivery. This review highlights the clinical significance of applying zein nanosystems for cancer theragnostic─moreover, the role of zein nanosystems for cancer drug delivery, anticancer agents, and gene therapy. Finally, the difficulties and potential uses of these NPs in cancer treatment and detection are discussed. This review will pave the way for researchers to develop theranostic strategies for precision medicine utilizing zein nanosystems.

Noninvasive Monitoring of Tissue Temperature Changes Induced by Focused Ultrasound Exposure using Sparse Expression of Ultrasonic Radio Frequency Echo Signals.

Noninvasive therapies such as focused ultrasound were developed to be used for cancer therapies, vessel bleeding, and drug delivery. The main purpose of focused ultrasound therapy is to affect regions of interest (ROI) of tissues without any injuries to surrounding tissues. In this regard, an appropriate monitoring method is required to control the treatment. This study is aimed to develop a noninvasive monitoring technique of focused ultrasound (US) treatment using sparse representation of US radio frequency (RF) echo signals. To this end, reasonable results in temperature change estimation in the tissue under focused US radiation were obtained by utilizing algorithms related to sparse optimization as orthogonal matching pursuit (OMP) and accompanying Shannon's entropy. Consequently, ex vivo tissue experimental tests yielded two datasets, including low-intensity focused US (LIFU) and high-intensity focused US (HIFU) data. The proposed processing method analyzed the ultrasonic RF echo signal and expressed it as a sparse signal and calculated the entropy of each frame. The results indicated that the suggested approach could noninvasively estimate temperature changes between 37°C and 47°C during LIFU therapy. In addition, it represented temperature changes during HIFU ablation at various powers, ranging from 10 to 130 W. The normalized mean square error of the proposed method is 0.28, approximately 2.15 on previous related methods. These results demonstrated that this novel proposed approach, including the combination of sparsity and Shanoon's entropy, is more feasible and effective in temperature change estimation than its predecessors.

Process optimization for gold nanoparticles biosynthesis by Streptomyces albogriseolus using artificial neural network, characterization and antitumor activities

Gold nanoparticles (GNPs) are highly promising in cancer therapy, wound healing, drug delivery, biosensing, and biomedical imaging. Furthermore, GNPs have anti-inflammatory, anti-angiogenic, antioxidants, anti-proliferative and anti-diabetic effects. The present study presents an eco-friendly approach for GNPs biosynthesis using the cell-free supernatant of Streptomyces albogriseolus as a reducing and stabilizing agent. The biosynthesized GNPs have a maximum absorption peak at 540 nm. The TEM images showed that GNPs ranged in size from 5.42 to 13.34 nm and had a spherical shape. GNPs have a negatively charged surface with a Zeta potential of − 24.8 mV. FTIR analysis identified several functional groups including C–H, –OH, C–N, amines and amide groups. The crystalline structure of GNPs was verified by X-ray diffraction and the well-defined and distinct diffraction rings observed by the selected area electron diffraction analysis. To optimize the biosynthesis of GNPs using the cell-free supernatant of S. albogriseolus, 30 experimental runs were conducted using central composite design (CCD). The artificial neural network (ANN) was employed to analyze, validate, and predict GNPs biosynthesis compared to CCD. The maximum experimental yield of GNPs (778.74 μg/mL) was obtained with a cell-free supernatant concentration of 70%, a HAuCl4 concentration of 800 μg/mL, an initial pH of 7, and a 96-h incubation time. The theoretically predicted yields of GNPs by CCD and ANN were 809.89 and 777.32 μg/mL, respectively, which indicates that ANN has stronger prediction potential compared to the CCD. The anticancer activity of GNPs was compared to that of doxorubicin (Dox) in vitro against the HeP-G2 human cancer cell line. The IC50 values of Dox and GNPs-based treatments were 7.26 ± 0.4 and 22.13 ± 1.3 µg/mL, respectively. Interestingly, treatments combining Dox and GNPs together showed an IC50 value of 3.52 ± 0.1 µg/mL, indicating that they targeted cancer cells more efficiently.

Gold Nanoparticles in Biomedicine: Advancements in Cancer Therapy, Drug Delivery, Diagnostics, and Tissue Regeneration

This review article provides an overview of the applications of gold nanoparticles (AuNPs) in biomedicine, focusing on their use in cancer therapy, drug delivery, diagnostics, and tissue regeneration. The unique optical properties of AuNPs allow for photothermal therapy, while their flexible surface chemistry enables functionalization with targeting ligands and therapeutics. Extensive research has demonstrated the effectiveness of AuNP-mediated photothermal ablation in various tumor models using near-infrared laser irradiation. Active tumor targeting has been achieved through the engineering of AuNP platforms with ligands such as transferrin, folic acid, and hyaluronic acid. Combining AuNPs with chemotherapy and immunotherapy has shown synergistic therapeutic benefits. Additionally, AuNPs have been explored as carriers for drugs and genes, with the design of stimuli-responsive polymers, lipids, and mesoporous silica enabling controlled release of cargo within cells. In diagnostics, the plasmonic properties of AuNPs have been leveraged for photoacoustic imaging, and clinical translation has been achieved in sentinel lymph node mapping. AuNP constructs have also overcome the limitations of the blood-brain barrier, allowing for delivery to the central nervous system. In regenerative medicine, functionalized AuNPs have demonstrated the ability to stimulate osteogenesis, myogenesis, angiogenesis, and tissue regeneration when combined with growth factors. They have also been found to accelerate wound healing through immunomodulation and promotion of revascularization. AuNP-based hydrogels and scaffolds provide structural support in tissue engineering applications. AuNP platforms exhibit versatility in addressing challenges in oncology, drug delivery, diagnostics, and regenerative therapies. Continued optimization of these strategies holds promise for their translation from the laboratory to clinical applications.

Molecular Dynamics Simulation Combined with Near-Field Electromagnetic Analysis for Ultrashort-Pulsed Light-Induced Plasmonic Nanobubbles.

Ultrashort-pulsed light-induced nanobubbles gain great attention in research fields such as cancer therapy, optical imaging, and drug delivery. However, the mechanism governing the nucleation and growth of nanobubbles remains controversial. In this study, a molecular dynamics simulation combined with near-field electromagnetic theory is developed to investigate the influence of the localized surface plasmon resonance effect (LSPR) on nanobubble nucleation under various time-length pulsed light and to reveal the energy transfer differences during the nanobubble generation process. The results show that when silver nanoparticles (NPs) are irradiated by a 5 ps shorter-pulsed light, the temperature of the water layer adjacent to the nanoparticle surpasses that of the nanoparticle itself and reaches the spinodal temperature. This leads to nanobubbles' rapid nucleation at approximately 20 ps, which is 80 ps earlier than that irradiated by a 100 ps longer-pulsed light. Comparatively, during longer-pulsed light irradiation, a slower increase in both the temperature of the silver NPs and the water layer results in delayed nucleation of nanobubbles. Therefore, the plasmonic nanobubbles (PNBs) were observed around in 74 and 100 ps when irradiated by 50 and 100 ps longer-pulsed light, respectively. Moreover, the result indicates that the LSPR-induced enhanced electric field by shorter-pulsed light (5 ps) is 2.1 × 1010 V/m, which can accelerate the motion of water molecules surrounding silver NPs, resulting in rapid generation of nanobubbles. However, the intensities of the resonant electric field drop to 5.6 × 109 and 5.0 × 109 V/m when the duration times of pulsed light are 50 and 100 ps, respectively. These results indicate that the energy transfer mechanism of plasmonic nanobubbles (PNBs) under ultrashort-pulsed light irradiation might be very different from that of thermally mediated nanobubbles (TNBs). This work provides new insights into understanding the generation of PNBs induced by ultrashort-pulsed light.

Therapeutic Peptides Are Preferentially Solubilized in Specific Microenvironments within PEG-PLGA Polymer Nanoparticles.

Polymeric nanoparticles are a highly promising drug delivery formulation. However, a lack of understanding of the molecular mechanisms that underlie their drug solubilization and controlled release capabilities has hindered the efficient clinical translation of such technologies. Polyethylene glycol-poly(lactic-co-glycolic) acid (PEG-PLGA) nanoparticles have been widely studied as cancer drug delivery vehicles. In this letter, we use unbiased coarse-grained molecular dynamics simulations to model the self-assembly of a PEG-PLGA nanoparticle and its solubulization of the anticancer peptide, EEK, with good agreement with previously reported experimental structural data. We applied unsupervised machine learning techniques to quantify the conformations that polymers adopt at various locations within the nanoparticle. We find that the local microenvironments formed by the various polymer conformations promote preferential EEK solubilization within specific regions of the NP. This demonstrates that these microenvironments are key in controlling drug storage locations within nanoparticles, supporting the rational design of nanoparticles for therapeutic applications.

Thermally Triggered Drug Delivery by Polyhedral Oligomeric Silsesquioxane Co -Conjugated with Gold as a Nano-Drug Carrier in Cancer Therapy

Nanoparticles can be modified with polymers and bioactive molecules aiming to achieve full efficiency in therapy and specific targeting. Polyhedral oligomeric silsesquioxane (POSS) is an organic-inorganic (RSiO1.5)8 hybrid material that consists of a –Si-O- inorganic core surrounded by tunable organic moieties. POSS is a highly symmetrical, cage-like structure, possible to add functional groups, both organic and inorganic in precision. POSS has been synthesized and characterized using FT-IR, 1H NMR, EDAX, SEM, and TEM. It has been developed along with the thiol end group and paves a space for cross-linked nanostructures formationPOSS-SH. Voids and spaces in the POSS cross-linked nanocarrier give enough space for drug loading up to 50 weight percentages. Here the therapy is done with the help of drug delivery application in an acidic medium found in the cancer cell site and acts as an internal trigger for drug releasefrom POSS. T h e Presence of thiol end terminal has a greater affinity for attachment of gold which in turn provides an add-on application of photo dynamic therapy this combination is gold POSS- SH-Au. Cell viability studies proved that the POSS nanostructures are biocompatible. Thedeveloped POSS nanostructures can even be activated at acidic conditions, used for sustained release of drugs at specific targets, and provide in-vivo stability until they reache the tumor site. ThePOSS-SH-Au resulted an improvement in aqueous stability as its chains have the tendency to wraparound the siloxane cage and prevent the water from getting close to the siloxane frameworks. Keywords: POSS, Crosslinked POSS nanodrug carrier, Cancer drug delivery, Gold nanoparticles, Upconverting nanoparticles.

Fabrication of pH-Responsive Amphiphilic Poly(Vinyl Alcohol–Methyl Methacrylate) Copolymer Nanoparticles for Application in Cancer Drug Delivery Systems

Fabrication of pH-Responsive Amphiphilic Poly(Vinyl Alcohol–Methyl Methacrylate) Copolymer Nanoparticles for Application in Cancer Drug Delivery Systems

Dehydrocurvularin-loaded mPEG-PLGA nanoparticles for targeted breast cancer drug delivery: preparation, characterization, in vitro, and in vivo evaluation

Dehydrocurvularin (DCV) is a promising lead compound for anti-cancer therapy. Unfortunately, the development of DCV-based drugs has been hampered by its poor solubility and bioavailability. Herein, we prepared a DCV-loaded mPEG-PLGA nanoparticles (DCV-NPs) with improved drug properties and therapeutic efficacy. The spherical and discrete particles of DCV-NPs had a uniform diameter of 101.8 ± 0.45 nm and negative zeta potential of −22.5 ± 1.12 mV (pH = 7.4), and its entrapment efficiency (EE) and drug loading (DL) were ∼53.28 ± 1.12 and 10.23 ± 0.30%, respectively. In vitro the release of DCV-NPs lasted for more than 120 h in a sustained-release pattern, its antiproliferation efficacy towards breast cancer cell lines (MCF-7, MDA-MB-231, and 4T1) was better than that of starting drug DCV, and it could be efficiently and rapidly internalised by breast cancer cells. In vivo DCV-NPs were gradually accumulated in tumour areas of mice and significantly suppressed tumour growth. In summary, loading water-insoluble DCV onto nanoparticles has the potential to be an effective agent for breast cancer therapy with injectable property and tumour targeting capacity.

Strategic Assessment of Boron-Enriched Carbon Dots/Naproxen: Diagnostic, Toxicity, and In Vivo Therapeutic Evaluation.

Cancer is a significant global public health concern, ranking as the leading cause of mortality worldwide. This study thoroughly explores boron-doped carbon dots (B-CDs) through a simple/rapid microwave-assisted approach and their versatile applications in cancer therapy. The result was highly uniform particles with an average diameter of approximately 4 nm. B-CDs exhibited notable properties, including strong fluorescence with a quantum yield of 33%. Colloid stability tests revealed their robustness within a pH range of 6-12, NaCl concentrations up to 0.5 M, and temperatures ranging from 30 to 60 °C. The study also delved into the kinetics of naproxen release from B-CDs as a drug delivery system. The loading efficacy of naproxen exceeded 55.56%. Under varying pH conditions, the release of naproxen from B-CDs conformed to the Peppas-Sahlin model, demonstrating the potential of Naproxen-loaded CDs for cancer drug delivery. In vitro cytotoxicity assessments, conducted using the CCK-8 Assay and flow cytometry, consistently indicated low toxicity with average cell viability exceeding 80%. An in vivo toxicity test on female mice administered 20 mg/kg of B-CDs for 31 days revealed reversible histological changes in the liver and kidneys, while the pancreas remained unaffected. Importantly, B-CDs did not impact the mice's physical behavior, body weight, or survival. In vivo experiments targeting benzo(a)pyrene-induced fibrosarcoma demonstrated the efficacy of B-CDs as naproxen carriers in the treatment of cancer. This in vivo study provides a thorough comprehension of B-CDs synthesis and toxicity and their potential applications in cancer therapy and drug delivery systems.

Stimuli‐Responsive Nanocarriers for Transcytosis‐Based Cancer Drug Delivery

Significant challenges persist in enhancing the delivery efficiency of tumor nanomedicines, predominantly due to the difficulty of successfully surpassing pathophysiological barriers. Enhancing tumor penetration of nanomedicines in such conditions represents a pivotal goal in advancing anticancer nanotherapeutics. Transcytosis emerges as a promising solution in this context, addressing the limitations of passive drug delivery. By harnessing diverse stimuli to induce transcytosis, nanocarriers can achieve precise drug delivery and deep tumor penetration, resulting in high therapeutic efficacy and reduced systemic exposure to the therapeutic compound. This review briefly examines various stimuli‐responsive nanosystems and offers an overview and outlook on the development of stimuli‐responsive nanocarriers for transcytosis‐based cancer drug delivery, aiming to provide informative insights for the design of nanomedicines capable of deep tissue penetration and enhanced therapeutic efficacy.

Marine-derived κ-carrageenan-coated zinc oxide nanoparticles for targeted drug delivery and apoptosis induction in oral cancer.

Kappaphycus alvarezii, a marine red algae species, has gained significant attention in recent years due to its versatile bioactive compounds. Among these, κ-carrageenan (CR), a sulfated polysaccharide, exhibits remarkable antimicrobial properties. This study emphasizes the synergism attained by functionalizing zinc oxide nanoparticles (ZnO NPs) with CR, thereby enhancing its antimicrobial efficacy and target specificity against dental pathogens. In this study, we synthesized ZnO-CR NPs and characterized them using SEM, FTIR, and XRD techniques to authenticate their composition and structural attributes. Moreover, our investigation revealed that ZnO-CR NPs possess better free radical scavenging capabilities, as evidenced by their effective activity in the DPPH and ABTS assay. The antimicrobial properties of ZnO-CR NPs were systematically assessed using a zone of inhibition assay against dental pathogens of S. aureus, S. mutans, E. faecalis, and C. albicans, demonstrating their substantial inhibitory effects at a minimal concentration of 50μg/mL. We elucidated the interaction between CR and the receptors of dental pathogens to further understand their mechanism of action. The ZnO-CR NPs demonstrated a dose-dependent anticancer effect at concentrations of 5μg/mL, 25μg/mL, 50μg/mL, and 100μg/mL on KB cells, a type of Human Oral Epidermal Carcinoma. The mechanism by which ZnO-CA NPs induced apoptosis in KB cells was determined by observing an increase in the expression of the BCL-2, BAX, and P53 genes. Our findings unveil the promising potential of ZnO-CR NPs as a candidate with significant utility in dental applications. The demonstrated biocompatibility, potent antioxidant and antiapoptotic activity, along with impressive antimicrobial efficacy position these NPs as a valuable resource in the ongoing fight against dental pathogens and oral cancer.

Functionalization of rice husk-derived mesoporous silica nanoparticles for targeted and imaging in cancer drug delivery.

Rice, a pivotal global food staple, annually accumulates vast amounts of rice husks, resulting in substantial environmental impact. Exploiting the high silica content in rice husk, our research aimed to recycle this agricultural byproduct to synthesize mesoporous silica nanoparticles (rMSNs). These nanoparticles were further modified to evaluate their potential as effective carriers for cancer drug delivery. rMSNs showed high biocompatibility, large surface area and porous structure as MSNs, making them excellent drug carriers. Further modifications were applied to rMSNs, such as the incorporation of the lanthanides europium and gadolinium into rMSNs, making them fluorescent and magnetic for detection and tracking using confocal fluorescence microscopy and magnetic resonance imaging. Additionally, folic acid and aptamer AS1411 were conjugated with rMSNs to enhance the targeting of cancer cells. HeLa cells exhibited higher uptake of camptothecin (CPT)-loaded rMSNs compared to normal fibroblast cells (L929). The linkage of disulfide bonds to rMSNs also allowed CPT to be carried by rMSNs and released intracellularly in the presence of the abundant reducing agent glutathione. The validation of rMSNs in vitro and in vivo proved their practical feasibility. Our findings indicate that low-cost rMSNs, derived from recycled agricultural waste, can replace highly valuable MSNs. Functionalized rMSNs exhibit promising capabilities in transporting clinical drugs to specific aberrant tissues and offering dual-targeting and dual-imaging functionalities for enhanced cancer therapy. © 2023 Society of Chemical Industry.

Cutting-edge approaches for targeted drug delivery in breast cancer: beyond conventional therapies.

Breast cancer is a global health challenge with staggering statistics underscoring its pervasive impact. The burden of this disease is measured in terms of its prevalence and the challenges it poses to healthcare systems, necessitating a closer look at its epidemiology and impact. Current breast cancer treatments, including surgery, chemotherapy, radiation therapy, and targeted therapies, have made significant strides in improving patient outcomes. However, they are not without limitations, often leading to adverse effects and the development of drug resistance. This comprehensive review delves into the complex landscape of breast cancer, including its incidence, current treatment modalities, and the inherent limitations of existing therapeutic approaches. It also sheds light on the promising role of nanotechnology, encompassing both inorganic and organic nanoparticles equipped with the ability to selectively deliver therapeutic agents to tumor sites, in the battle against breast cancer. The review also addresses the emerging therapies, their associated challenges, and the future prospects of targeted drug delivery in breast cancer management.

Modelling and breaking down the biophysical barriers to drug delivery in pancreatic cancer.

The pancreatic ductal adenocarcinoma (PDAC) stroma and its inherent biophysical barriers to drug delivery are central to therapeutic resistance. This makes PDAC the most prevalent pancreatic cancer with poor prognosis. The chemotherapeutic drug gemcitabine is used against various solid tumours, including pancreatic cancer, but with only a modest effect on patient survival. The growing PDAC tumour mass with high densities of cells and extracellular matrix (ECM) proteins, i.e., collagen, results in high interstitial pressure, leading to vasculature collapse and a dense, hypoxic, mechanically stiff stroma with reduced interstitial flow, critical to drug delivery to cells. Despite this, most drug studies are performed on cellular models that neglect these biophysical barriers to drug delivery. Microfluidic technology offers a promising platform to emulate tumour biophysical characteristics with appropriate flow conditions and transport dynamics. We present a microfluidic PDAC culture model, encompassing the disease's biophysical barriers to therapeutics, to evaluate the use of the angiotensin II receptor blocker losartan, which has been found to have matrix-depleting properties, on improving gemcitabine efficacy. PDAC cells were seeded into our 5-channel microfluidic device for a 21-day culture to mimic the rigid, collagenous PDAC stroma with reduced interstitial flow, which is critical to drug delivery to the cancer cells, and for assessment with gemcitabine and losartan treatment. With losartan, our culture matrix was more porous with less collagen, resulting in increased hydraulic conductivity of the culture interstitial space and improved gemcitabine effect. We demonstrate the importance of modelling tumour biophysical barriers to successfully assess new drugs and delivery methods.

Advancing Drug Delivery in Colorectal Cancer: A Comprehensive Exploration of Nanotechnology, Experimental Models, and Production Process Simulation

Colorectal cancer (CRC) remains a major global health challenge as the third most common cancer worldwide. Survival relies heavily on early diagnosis and treatment before progression to metastasis. Employing nanotechnology for targeted drug delivery shows promise to enhance therapeutic efficacy and tolerability in CRC. Diverse nanoparticle platforms offer unique advantages as CRC drug carriers with tunable properties like improved pharmacokinetics, stability, sustained release, and tumor cell uptake through endocytosis or transcytosis. Key platforms highlighted include liposomes, polymeric micelles, solid lipid nanoparticles, nanodiscs, cubosomes, and polysaccharide particles. In vivo testing is warranted to translate multiparameter optimized carrier designs to clinical applications. Simulations help predict carrier localization, biodistribution, controlled release, and optimal formulations. Overall, nanomedicine promises more targeted therapeutic delivery to improve survival for CRC patients, especially those with advanced or metastatic disease. However, realizing this potential requires additional pharmacodynamic studies alongside mechanistic clarification and carrier optimization to progress designs to clinical evaluation. Advancing personalized, targeted nanotechnology-enabled treatment options remains imperative.

Strategies for Small Extracellular Vesicle-Based Cancer Immunotherapy.

Extracellular vesicles (EVs) are lipid bilayer-enclosed vesicles released by cells. EVs encapsulate proteins and nucleic acids of their parental cell and efficiently deliver the cargo to recipient cells. These vesicles act as mediators of intercellular communication and thus play a crucial role in various physiological and pathological processes. Moreover, EVs hold promise for clinical use. They have been explored as drug delivery vehicles, therapeutic agents, and targets for disease diagnosis. In the landscape of cancer research, while strides have been made in EV-focused cancer physiopathology, liquid biopsy, and drug delivery, the exploration of EVs as immunotherapeutic agents may not have seen substantial progress to date. Despite promising findings reported in cell and animal studies, the clinical translation of EV-based cancer immunotherapeutics encounters challenges. Here, we review the existing strategies used in EV-based cancer immunotherapy, aiming to propel the development of this emerging yet crucial field.

Advanced Technologies of Drug Delivery to the Posterior Eye Segment Targeting Angiogenesis and Ocular Cancer.

Retinoblastoma (RB), a childhood retinal cancer is caused due to RB1 gene mutation which affects the child below 5 years of age. Angiogenesis has been proven its role in RB metastasis due to the presence of vascular endothelial growth factor (VEGF) in RB cells. Therefore, exploring angiogenic pathway by inhibiting VEGF in treating RB would pave the way for future treatment. In preclinical studies, anti-VEGF molecule have shown their efficacy in treating RB. However, treatment requires recurrent intra-vitreal injections causing various side effects along with patient nonadherence. As a result, delivery of anti-VEGF agent to retina requires an ocular delivery system that can transport it in a non-invasive manner to achieve patient compliance. Moreover, development of these type of systems are challenging due to the complicated physiological barriers of eye. Adopting a non-invasive or minimally invasive approach for delivery of anti-VEGF agents would not only address the bioavailability issues but also improve patient adherence to therapy overcoming the side effects associated with invasive approach. The present review focuses on the eye cancer, angiogenesis and various novel ocular drug delivery systems that can facilitate inhibition of VEGF in the posterior eye segment by overcoming the eye barriers.

Stabilization versus competing de-metalation, trans-metalation and (cyclo)-dehydrogenation of Pd porphyrins at a copper surface.

Metal-porphyrins are studied intensively due their potential applications, deriving from the variety of electronic and chemical properties, tunable by selecting metal centers and functional groups. Metalation, de- and trans-metalation processes are fundamental in this sense to investigate both the synthesis and the stability of these molecular building blocks. More specifically, Pd coordination in tetrapyrroles revealed to be potentially interesting in the fields of cancer therapy, drug delivery and light harvesting. Thus, we focused on the stability of palladium tetraphenyl porphyrins (PdTPPs) on a copper surface by means of combined spectroscopy and microscopy approaches. We find that PdTPPs undergo coverage-dependent trans-metalation accompanied by steric rearrangements already at room temperature, and fully trans-metalate to CuTPPs upon mild annealing. Side reactions such as (cyclo)-dehydrogenation and structural reorganization affect the molecular layer, with Pd-Cu alloying and segregation occurring at higher temperature. Instead, oxygen passivation of the Cu support prevents the metal-involving reactions, thus preserving the layer and increasing the chemical and temperature stability of the Pd porphyrins.