Enhanced Cancer Therapy Research Articles

Developing a novel P-glycoprotein inhibitor and pairing it with oral paclitaxel liposomes for enhanced cancer therapy

The mucus layer and intestine epithelium pose challenges to the bioavailability of orally administered paclitaxel (PTX). A novel P-glycoprotein inhibitor, (S)-2-decanoylamino-3-(1-naphthyl)propionyl-leucyl-valine (PgpI), was synthesized in this study. Its structure was characterized using 1H NMR, 13C NMR, ESI-MS and IR spectroscopies. The efficacy and in vivo toxicity of PgpI were comprehensively evaluated by R8-PEG@PLs&PgpI, i.e., the oral combination of PgpI and octaarginine R8-PEG-DSPE modified PTX liposomes (R8-PEG@PLs), for lung cancer treatment. The joint forms between PgpI and R8-PEG@PLs were investigated and the affinity of PgpI for intestinal P-glycoprotein remained unaffected when combined externally with R8-PEG@PLs (R8-PEG@PLs&PgpI), compared to the diminished affinity for internal combination. The primary endocytic pathway for R8-PEG@PLs&PgpI in Caco-2 cells was the lipid raft, with increased percentage of macropinocytosis compared to unmodified PTX liposomes (PLs). The established physiology-based cellular kinetic models revealed that the net internalization rate of PTX was 2.3 times higher in R8-PEG@PLs&PgpI than in PLs, correlating with in vivo 2.2 times of antitumor rate. R8-PEG@PLs&PgpI may address the deficits of PLs in human lung A549 tumor-bearing mice due to the lower drug concentration than in normal mice. The external combination of R8-PEG@PLs&PgpI, offering maximal efficacy and security of PgpI, is promising for oral PTX delivery.

Disrupting Tumour Niches: Advanced Strategies for Targeting the Tumour Microenvironment in Cancer Therapy

Abstract: The review paper provides an extensive overview of strategies for targeting the tumour microenvironment (TME) to enhance cancer therapy. It begins by underscoring the importance of profiling and comprehending the TME through advanced technologies like organ chips and artificial intelligence. The paper discusses multiple approaches to modulate the pro-tumour TME, including strategies for eliminating, normalizing, and targeting tumour cells. It delves into specific aspects such as cancer-associated fibroblasts, extracellular matrix, hypoxia, acidosis, neovascularisation, tumour-infiltrating T cells, the immune system, exosomes, tumour-associated neutrophils, and tumour angiogenesis. Emphasis is placed on the necessity of a multifaceted approach to effectively target the complex and dynamic TME, which plays a crucial role in tumour progression and therapeutic resistance. The conclusion highlights the significant impact of the TME on cancer therapy and identifies promising research and clinical application avenues. The paper underscores the shift in cancer treatment paradigms, advocating for strategies that address the intricate interactions within the TME to improve therapeutic outcomes.

Theranostic Nanomaterials to Overcome the Challenges in Peptide-based Cancer Therapy

: Globally, the number of cancer cases and death rates are increasing, making it necessary to develop new and improved medications for the treatment of cancer.Owing to a broad range of physio-chemical properties, Antimicrobial Peptides (AMPs) possessing tumoricidal properties and Anticancer Peptides (ACPs) are promising alternatives for enhanced cancer therapy. Recently, biopharmaceuticals have changed the rules of radiation therapy and chemotherapy by introducing peptide therapy for cancer treatments. However, several limitations obstruct the clinical efficacy of peptide-based cancer therapies, which include limited target specificity, oral intake, and half-life payloads. The integration of theranostic nanomaterials could be facilitated as a transformative strategy to address these challenges and enhance the potential of peptide-based cancer therapy. Increasing applications of recent times of peptide-nano hybrids have addressed the crucial issues related to conventional peptide-based drug therapy by enhancing the druggability. This review aims to explore the impact of nano-formulated peptides as an anticancer agent, highlighting the involvement of nanotechnology as an enabling tool.

Folate-Functionalized Chitosan-PLGA Nanoparticles: A Novel approach for targeted osthole delivery in pancreatic cancer

Efficient drug delivery systems targeting cancer cells are crucial for enhancing cancer therapy. In this study, we developed PLGA nanoparticles coated with folate-conjugated chitosan (osthole-PLGA-NPs/CS-FA) to deliver osthole to cancer cells and investigated its inhibitory and molecular signaling mechanisms in the PANC-1 pancreatic cancer cell line. Field emission scanning electron microscopy (FESEM) revealed that osthole-PLGA-NPs/CS-FA had a spherical structure with a uniform size distribution. Dynamic light scattering (DLS) analysis showed an average size of 171.76 nm, a dispersion index 0.26, and a surface charge of + 33.08 mV, indicating stability and uniform dispersion. Fourier-transform infrared (FTIR) spectrum analysis confirmed the successful incorporation of osthole into the PLGA nanoparticles, with an encapsulation efficiency of 93.12 %. These physicochemical properties suggest efficient cellular uptake and targeted delivery. The antioxidant potential of osthole-PLGA-NPs/CS-FA was evaluated using the ABTS assay, showing concentration-dependent inhibition of free radicals with an IC50 value of 172.95 μg/mL. The anticancer properties were assessed using the MTT assay, demonstrating a significant and concentration-dependent cytotoxic effect on PANC-1 cells (IC50 = 31.2 μg/mL) with minimal impact on normal human foreskin fibroblast (HFF) cells. DAPI staining and flow cytometry analyses confirmed a concentration-dependent increase in apoptosis in PANC-1 cells. The nanoparticles induced upregulation of Bax and downregulation of Bcl2, indicating activation of the intrinsic mitochondrial apoptotic pathway. The anti-angiogenic activity of osthole-PLGA-NPs/CS-FA was evaluated using the chick chorioallantoic membrane (CAM) assay. The results showed significant inhibition of angiogenesis in a concentration-dependent manner, starting at 40 μg/mL and increasing up to 120 μg/mL. In conclusion, osthole-PLGA-NPs/CS-FA nanoparticles exhibit promising potential for targeted pancreatic cancer therapy by enhancing cellular uptake, inducing apoptosis, and inhibiting angiogenesis.

Innovative Fluorescent Polymers in Niosomal Carriers: A Novel Approach to Enhancing Cancer Therapy and Imaging.

Cancer is anticipated to become the pioneer reason of disease-related deaths worldwide in the next two decades, underscoring the urgent need for personalized and adaptive treatment strategies. These strategies are crucial due to the high variability in drug efficacy and the tendency of cancer cells to develop resistance. This study investigates the potential of theranostic nanotechnology using three innovative fluorescent polymers (FP-1, FP-2, and FP-3) encapsulated in niosomal carriers, combining therapy (chemotherapy and radiotherapy) with fluorescence imaging. These cargoes are assessed for their cytotoxic effects across three cancer cell lines (A549, MCF-7, and HOb), with further analysis to determine their capacity to augment the effects of radiotherapy using a Linear Accelerator (LINAC) at specific doses. Fluorescence microscopy is utilized to verify their uptake and localization in cancerous versus healthy cell lines. The results confirmed that these niosomal cargoes not only improved the antiproliferative effects of radiotherapy but also demonstrate the practical application of fluorescent polymers in in vitro imaging. This dual function underscores the importance of dose optimization to maximize therapeutic benefits while minimizing adverse effects, thereby enhancing the overall efficacy of cancer treatments.

Multi-factor optimization and interaction analysis for enhanced nanobubble formulation and performance of Dasatinib

The objective of this study was to develop and optimize PLGA nanobubbles as a delivery system for dasatinib. In this study, we developed nanobubbles with a perfluoropentane core and a PLGA outer shell, optimizing their properties using a three-level Box-Behnken design. We thoroughly examined the physical and chemical attributes of dasatinib-loaded nanobubbles, including size, surface charge, and structure, and assessed drug encapsulation and release, as well as investigating cell uptake and antitumor effectiveness. The encapsulation efficiency, particle size, and zeta potential of the nanobubbles varied from 15.12 % to 69.23 %, 96.78 nm–767.72 nm, and −38.56 mV to −12.34 mV, respectively, in 29 trials using a Box-Behnken design. Employing Response Surface Methodology, we optimized the formulation, resulting in an ideal combination: 160.35 mg dasatinib, 500 mg PLGA, 2.0 % w/v PVA, and stirring at 6000 rpm, achieving a high global desirability value of 0.971. These nanobubbles demonstrated an encapsulation efficiency of 80.12 % and a loading capacity of 24.34 %, with a low viscosity of 6.1 cP. Nanobubbles showed notable differences in drug release with and without ultrasound. Under sonication, 59.42 % of dasatinib was released in 6 h compared to 35.34 % without sonication, and after 24 h, 76.89 % was released without ultrasound, while nearly 99.58 % was released with ultrasound. Stability tests at different temperatures showed consistent encapsulation efficiency and particle size, especially at lower temperatures. Safety evaluations indicated no hemolysis, and cellular uptake studies revealed around a 2.5-fold increase in fluorescence intensity in cells exposed to Dasatinib Nanobubbles with ultrasound. Cytotoxicity tests demonstrated enhanced sensitivity, with IC50 values of 86.82 μM for free dasatinib, 63.58 μM for nanobubbles without ultrasound, and 44.58 μM for nanobubbles with ultrasound. The PLGA nanobubbles efficiently encapsulated dasatinib, boosting cellular uptake and cytotoxicity, underscoring their potential for enhanced cancer therapy, particularly with ultrasound.

Advanced Analytical Techniques for Characterizing Nanoparticle-Drug Conjugates: Enhancing Cancer Therapy through Precision and Innovation

Advanced Analytical Techniques for Characterizing Nanoparticle-Drug Conjugates: Enhancing Cancer Therapy through Precision and Innovation

Design of a Membrane-Anchored DNAzyme-Based Molecular Machine for Enhanced Cancer Therapy by Customized Cascade Regulation.

Synthetic DNAzyme-based structures enable dynamic cell regulation. However, engineering an effective and targeted DNAzyme-based structure to perform customizable multistep regulation remains largely unexplored. Herein, we designed a membrane-anchored DNAzyme-based molecular machine to implement dynamic inter- and intracellular cascade regulation, which realizes efficient T-cell/cancer cell interactions and subsequent receptor mediated cancer cell uptake. Using CD8+ T-cells and HeLa cancer cells as a proof of concept, we demonstrate that the designed DNAzyme-based molecular machine enables customized cascade regulation including (1) specific recognition between T-cells and cancer cells, (2) specific response and fluorescence sensing upon extracellular stimuli, and (3) cascade regulation including intercellular distance shortening, cell-cell communication, and intracellular delivery of anticancer drugs. Together, this work provides a promising pathway for customized cascade cell regulation based on a DNAzyme-based molecular machine, which enables enhanced cancer therapy by combining T-cell immunotherapy and chemotherapy.

A region-confined PROTAC nanoplatform for spatiotemporally tunable protein degradation and enhanced cancer therapy

The antitumor performance of PROteolysis-TArgeting Chimeras (PROTACs) is limited by its insufficient tumor specificity and poor pharmacokinetics. These disadvantages are further compounded by tumor heterogeneity, especially the presence of cancer stem-like cells, which drive tumor growth and relapse. Herein, we design a region-confined PROTAC nanoplatform that integrates both reactive oxygen species (ROS)-activatable and hypoxia-responsive PROTAC prodrugs for the precise manipulation of bromodomain and extraterminal protein 4 expression and tumor eradication. These PROTAC nanoparticles selectively accumulate within and penetrate deep into tumors via response to matrix metalloproteinase-2. Photoactivity is then reactivated in response to the acidic intracellular milieu and the PROTAC is discharged due to the ROS generated via photodynamic therapy specifically within the normoxic microenvironment. Moreover, the latent hypoxia-responsive PROTAC prodrug is restored in hypoxic cancer stem-like cells overexpressing nitroreductase. Here, we show the ability of region-confined PROTAC nanoplatform to effectively degrade BRD4 in both normoxic and hypoxic environments, markedly hindering tumor progression in breast and head-neck tumor models.

Self-Assembled Chemo/Photothermal Nanoplatform for Enhanced Cancer Therapy: Sensitizing Photothermal Ablation and Reprogramming Inflammatory Microenvironment

Self-Assembled Chemo/Photothermal Nanoplatform for Enhanced Cancer Therapy: Sensitizing Photothermal Ablation and Reprogramming Inflammatory Microenvironment

A Mitochondria-Targeted Photosensitizer for Combined Pyroptosis and Apoptosis with NIR-II Imaging/Photoacoustic Imaging-Guided Phototherapy.

Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, a lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential in cancer treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation of photosensitizers (PSs), many PSs lack specific subcellular targets and are limited to the first near-infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep-penetrating, organelle-targeted pyroptosis-mediated phototherapy is essential for cancer treatment strategies. Here, we synthesized four molecules with varying benzene ring numbers in thiopyrylium structures to preliminarily explore their photodynamic properties. The near-infrared-II (NIR-II) PS Z1, with a higher benzene ring count, exhibited superior ROS generation and mitochondria-targeting abilities, and a large Stokes shift. Through nano-precipitation method, Z1 nanoparticles (NPs) also demonstrated high ROS generation (especially type-I ROS) upon 808 nm laser irradiation, leading to efficient mitochondria dysfunction and combined pyroptosis and apoptosis. Moreover, they exhibited exceptional tumor-targeting ability via NIR-II fluorescence imaging (NIR-II FI) and photoacoustic imaging (PAI). Furthermore, Z1 NPs-mediated phototherapy effectively inhibited tumor growth with minimal adverse effects. Our findings offer a promising strategy for cancer therapy, warranting further preclinical investigations in PDT.

A Mitochondria‐Targeted Photosensitizer for Combined Pyroptosis and Apoptosis with NIR‐II Fluorescence/Photoacoustic Imaging‐Guided Phototherapy

Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, a lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential in cancer treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation of photosensitizers (PSs), many PSs lack specific subcellular targets and are limited to the first near‐infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep‐penetrating, organelle‐targeted pyroptosis‐mediated phototherapy is essential for cancer treatment strategies. Here, we synthesized four molecules with varying benzene ring numbers in thiopyrylium structures to preliminarily explore their photodynamic properties. The near‐infrared‐II (NIR‐II) PS Z1, with a higher benzene ring count, exhibited superior ROS generation and mitochondria‐targeting abilities, and a large Stokes shift. Through nano‐precipitation method, Z1 nanoparticles (NPs) also demonstrated high ROS generation (especially type‐I ROS) upon 808 nm laser irradiation, leading to efficient mitochondria dysfunction and combined pyroptosis and apoptosis. Moreover, they exhibited exceptional tumor‐targeting ability via NIR‐II fluorescence imaging (NIR‐II FI) and photoacoustic imaging (PAI). Furthermore, Z1 NPs‐mediated phototherapy effectively inhibited tumor growth with minimal adverse effects. Our findings offer a promising strategy for cancer therapy, warranting further preclinical investigations in PDT.

Carrier‐Free Disulfiram Based Nanomedicine for Enhanced Cancer Therapy

AbstractNumerous nanomedicines have been developed to improve the efficiency and safety of conventional anticancer drugs. However, the carrier materials and intricate nature of multifunctional design always hindered the clinical transformation of nanomedicines. Herein, a novel carrier‐free anticancer nanomedicine (CFDC) with tailored morphologies including nanodots, nanorod and nanosheet were prepared using the clinically approved anti‐alcoholism drug disulfiram (DSF) via supramolecular assembly process. Our study reveals that CFDC induces the production of reactive oxygen species and activates the downstream apoptosis‐related c‐Jun N‐terminal kinase (JNK) and p‐38 pathway. In addition, the CFDC effectively counteract the inhibitory effect of NF‐κB expression on ROS‐induced cellular cytotoxicity, ultimately resulting in enhanced cell apoptosis, which is not achievable by pure DSF and the simply mixing of DSF and Cu2+ (DSF+Cu). Notably, the CFDC exhibits 3.1‐, 3.0‐folds increased on cancer cell DNA damage compared with the DSF, and DSF+Cu groups. In vivo experiments conducted on breast‐ or prostate‐bearing mice modals demonstrated that the CFDC exhibits a higher efficacy in suppressing the tumor growth. The remarkable drug delivery efficiency and better anticancer effect of CFDC nanodrug provide promising prospects for the clinical transformation of DSF based nanodrug in cancer therapy.

NIR-II light-powered core-shell prodrug nanomotors enhance cancer therapy through synergistic oxidative stress-photothermo modulation

Near-infrared-II (NIR-II) photothermal therapy is emerging as a cutting-edge modality for tumor ablation due to its good biosafety, high penetration ability and spatiotemporal controllability. Despite efforts, establishing a link between cellular metabolic regulation and photothermal performance is still promising in synergistic cancer therapy. Herein, we developed a core-shell semiconducting polymer@metal-phenolic network (SP@GFP) nanomotor by assembling diphenol-terminated cisplatin prodrug ligand (cPt-DA) and iron (III) (Fe3+) through metal coordination on SP particles in the presence of GOx and DSPE-PEG-cRGD, for NIR-II-propelled self-propulsion and synergistic cancer therapy. Remotely driving the SP@GFP nanomotor with an NIR-II laser through a thermophoresis mechanism would allow for in-depth penetration and accumulation. The synergistic photothermal effect and continuous Fe2+-mediated ROS generation of SP@GFP nanomotor could activate photothermal, chemotherapeutic effects and ferroptosis pathway for cancer cells through reshaping cellular metabolic pathways (HSP and GPX4). By combining the concepts of chemotherapeutic prodrugs, catalytic ROS generation, photothermal response and cellular metabolic regulation, the NIR-II laser-controlled core-shell SP@GFP nanomotor displayed improved outcomes for enhanced cancer therapy through synergistic oxidative stress-photothermo modulation. Statement of significance•A NIR-II-powered core-shell SP@GFP prodrug nanomotor was constructed through metal coordination assembly for enhanced cancer therapy;•NIR-II laser propelled the propulsion of SP@GFP nanomotor through thermophoresis mechanism for in depth penetration and accumulation.•Therapeutic outcomes were improved through synergistic modulating oxidative stress and photothermal performance.

Bioactive poly(amino acid)s for multi-modal cancer therapy.

The interplay between the tumor cells and their microenvironments is as inseparable as the relationship between "seeds" and "soil." The tumor microenvironments (TMEs) exacerbate malignancy by enriching malignant cell subclones, generating extracellular matrices, and recruiting immunosuppressive cells, thereby diminishing the efficacy of clinical therapies. Modulating TMEs has emerged as a promising strategy to enhance cancer therapy. However, the existing drugs used in clinical settings do not target the TMEs specifically, underscoring the urgent need for advanced strategies. Bioactive materials present unique opportunities for modulating TMEs. Poly(amino acid)s with precisely controllable structures and properties offer exceptional characteristics, such as diverse structural units, excellent biosafety, ease of modification, sensitive biological responsiveness, and unique secondary structures. These attributes hold significant potential for the modulation of TMEs and clinical applications further. Consequently, developing bioactive poly(amino acid)s capable of modulating the TMEs by elucidating structure-activity relationships and mechanisms is a promising approach for innovative clinical oncology therapy. This review summarizes the recent progress of our research team in developing bioactive poly(amino acid)s for multi-modal tumor therapy. First, a brief overview of poly(amino acid) synthesis and their advantages as nanocarriers is provided. Subsequently, the pioneering research of our research group on synthesizing the biologically responsive, dynamically allosteric, and immunologically effective poly(amino acid)s are highlighted. These poly(amino acid)s are designed to enhance tumor therapy by modulating the intracellular, extracellular matrix, and stromal cell microenvironments. Finally, the future development of poly(amino acid)s is discussed. This review will guide and inspire the construction of bioactive poly(amino acid)s with promising clinical applications in cancer therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Biology-Inspired Nanomaterials > Peptide-Based Structures.

Exploring Disulfiram's Anticancer Potential: PLGA Nano-Carriers for Prolonged Drug Delivery and Potential Improved Therapeutic Efficacy.

Disulfiram (DS) has been shown to have potent anti-cancer activity; however, it is also characterised by its low water solubility and rapid metabolism in vivo. Biodegradable polylactic-co-glycolic acid (PLGA) polymers have been frequently employed in the manufacturing of PLGA nano-carrier drug delivery systems. Thus, to develop DS-loaded PLGA nanoparticles (NPs) capable of overcoming DS's limitations, two methodologies were used to formulate the NPs: direct nanoprecipitation (DNP) and single emulsion/solvent evaporation (SE), followed by particle size reduction. The DNP method was demonstrated to produce NPs of superior characteristics in terms of size (151.3 nm), PDI (0.083), charge (-37.9 mV), and loading efficiency (65.3%). Consequently, NPs consisting of PLGA and encapsulated DS coated with mPEG2k-PLGA at adjustable ratios were prepared using the DNP method. Formulations were then characterised, and their stability in horse serum was assessed. Results revealed the PEGylated DS-loaded PLGA nano-carriers to be more efficient; hence, in-vitro studies testing these formulations were subsequently performed using two distinct breast cancer cell lines, showing great potential to significantly enhance cancer therapy.

Design of Polymeric Nanoparticles for Theranostic Delivery of Capsaicin as Anti-Cancer Drug and Fluorescent Nitrogen-Doped Graphene Quantum Dots.

In recent years, multifunctional nanocarriers that provide simultaneous drug delivery and imaging have attracted enormous attention, especially in cancer treatment. In this research, we designed a biocompatible fluorescent multifunctional nanocarrier for the co-delivery of capsaicin (CPS) and nitrogen-doped graphene quantum dots (N-GQDs) using the pH sensitive amphiphilic block copolymer (poly(2-ethyl-2-oxazoline)-b-poly(ε-caprolactone), PEtOx-b-PCL). The effects of the critical formulation parameters (the amount of copolymer, the concentration of poly(vinyl alcohol) (PVA) as a stabilizing agent in the inner aqueous phase, and volume of the inner phase) were evaluated to achieve optimal nanoparticle properties using Central Composite Design (CCD). The optimized nanoparticles demonstrated a desirable size distribution (167.8±1.4nm) with a negative surface charge (-19.9±0.4) and a suitable loading capacity for capsaicin (70.80±0.05%). The CPS & N-GQD NPs were found to have remarkable toxicity on human breast adenocarcinoma cell line (MCF-7). The solid fluorescent signal was acquired from cells containing multifunctional nanoparticles, according to the confocal microscope imaging results, confirming the significant cellular uptake. This research illustrates the enormous potential for cellular imaging and enhanced cancer therapy offered by multifunctional nanocarriers that combine drug substances with the novel fluorescent agents. This article is protected by copyright. All rights reserved.

PEG-lipid-modified agonistic antibody against tumor necrosis factor receptor family elicits superior apoptosis-inducing activity against human carcinoma

We have recently developed a novel PEG-lipid-modified antibody to enhance the induction of apoptosis by the agonistic antibody. The chemically modified TRA-8 antibody [anti-death receptor 5 (DR5) antibody] with PEG-lipid (DSPE-PEG) demonstrated significant cytotoxic activity in vitro without the need for crosslinking with a secondary antibody, which is typically required. We investigated the correlation between the PEG-lipid structure and the cytotoxic activity of the modified antibodies by varying the PEG length or lipid structure. However, when the DSPE-PEG-modified TRA-8 antibody was incubated with plasma, it lost its cytotoxic activity, likely due to degradation in the DSPE-PEG component. Nevertheless, by designing new PEG-lipids that are intended to be resistant to enzymatic degradation, we were able to prevent this degradation and restore the cytotoxic activity of the modified antibody. These findings provide valuable insights for the design of PEG-lipid-modified antibodies and suggest their potential effectiveness in enhancing cancer therapy.

Evodiamine and its nano-based approaches for enhanced cancer therapy: recent advances and challenges.

Evodiamine is a bioactive alkaloid extracted from the Evodia rutaecarpa plant. It has various pharmacological effects including anti-cancer, anti-bacterial, anti-obesity, anti-neurodegenerative, anti-depressant, and cardiac protective properties. Evodiamine demonstrates potent anti-cancer activity by inhibiting the proliferation of cancer cells in vitro and in vivo. Despite the health-promoting properties of evodiamine, its clinical use is hindered by low water solubility, poor bioavailability, and toxicity. Thus, there is a need to develop alternative drug delivery systems for evodiamine to enhance its solubility, permeability, and stability, as well as to facilitate targeted, prolonged, and controlled drug release. Nanocarriers can increase the therapeutic potential of evodiamine in cancer therapy while reducing adverse side effects. To date, numerous attempts have been made through the development of smart nanocarriers to overcome the drawbacks of evodiamine. This review focuses on the pharmacological applications, anti-cancer mechanisms, and limitations of evodiamine. Various nanocarriers, including lipid-based nanoparticles, polymeric nanoparticles, cyclodextrins, and so forth, have been discussed extensively for evodiamine delivery. Nano-drug delivery systems could increase the solubility, bioavailability, stability, and therapeutic efficacy of evodiamine. This review aims to present a comprehensive and critical evaluation of several nano-formulations of evodiamine for cancer therapy. © 2024 Society of Chemical Industry.

Noninvasive therapy of brain cancer using a unique systemic delivery methodology with a cancer terminator virus.

Primary, glioblastoma, and secondary brain tumors, from metastases outside the brain, are among the most aggressive and therapeutically resistant cancers. A physiological barrier protecting the brain, the blood-brain barrier (BBB), functions as a deterrent to effective therapies. To enhance cancer therapy, we developed a cancer terminator virus (CTV), a unique tropism-modified adenovirus consisting of serotype 3 fiber knob on an otherwise Ad5 capsid that replicates in a cancer-selective manner and simultaneously produces a potent therapeutic cytokine, melanoma differentiation-associated gene-7/interleukin-24(MDA-7/IL-24). A limitation of the CTV and most other viruses, including adenoviruses, is an inability to deliver systemically to treat brain tumors because of the BBB, nonspecific virus trapping, and immune clearance. These obstacles to effective viral therapy of brain cancer have now been overcome using focused ultrasound with a dual microbubble treatment, the focused ultrasound-double microbubble(FUS-DMB) approach. Proof-of-principle is now provided indicating that the BBB can be safely and transiently opened, and the CTV can then be administered in a second set of complement-treated microbubbles and released in the brain using focused ultrasound. Moreover, the FUS-DMB can be used to deliver the CTV multiple times in animals with glioblastoma growing in their brain thereby resulting in a further enhancement in survival. This strategy permits efficient therapy of primary and secondary brain tumors enhancing animal survival without promoting harmful toxic or behavioral side effects. Additionally, when combined with a standard of care therapy, Temozolomide, a further increase in survival is achieved. The FUS-DMB approach with the CTV highlights a noninvasive strategy to treat brain cancers without surgery. This innovative delivery scheme combined with the therapeutic efficacy of the CTV provides a novel potential translational therapeutic approach for brain cancers.