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Current Pharmaceutical Biotechnology 2024Colorectal cancer (CRC) is a complex and multifactorial disorder in middle-aged people. Several modern medicines are available for treating and preventing it. However,... (Review)
Review
Colorectal cancer (CRC) is a complex and multifactorial disorder in middle-aged people. Several modern medicines are available for treating and preventing it. However, their therapeutic uses are limited due to drawbacks, such as gastric perforation, diarrhea, intestinal bleeding, abdominal cramps, hair loss, nausea, vomiting, weight loss, and adverse reactions. Hence, there is a continuous quest for safe and effective medicines to manage human health problems, like CRC. In this context, herbal medicines are considered an alternative disease control system. It has become popular in countries, like American, European, and Asian, due to its safety and effectiveness, which has been practiced for 1000 years. During the last few decades, herbal medicines have been widely explored through multidisciplinary fields for getting active compounds against human diseases. Several herbal bioactives, like curcumin, glycyrrhizin, paclitaxel, chlorogenic acid, gallic acid, catechin, berberine, ursolic acid, betulinic acid, chrysin, resveratrol, quercetin, etc., have been found to be effective against CRC. However, their pharmacological applications are limited due to low bioavailability and therapeutic efficacy apart from their several health benefits. An effective delivery system is required to increase their bioavailability and efficacy. Therefore, targeted novel drug delivery approaches are promising for improving these substances' solubility, bioavailability, and therapeutic effects. Novel carrier systems, such as liposomes, nanoparticles, micelles, microspheres, dendrimers, microbeads, and hydrogels, are promising for delivering poorly soluble drugs to the target site, i.e., the colon. Thus, the present review is focused on the pathophysiology, molecular pathways, and diagnostic and treatment approaches for CRC. Moreover, an emphasis has been laid especially on herbal bioactive-based novel delivery systems and their clinical updates.
Topics: Humans; Colorectal Neoplasms; Drug Carriers; Animals; Nanoparticles; Drug Delivery Systems; Phytochemicals; Antineoplastic Agents, Phytogenic
PubMed: 38807329
DOI: 10.2174/0113892010242028231002075512 -
Acta Biomaterialia May 2024The combination of ferroptosis, cuproptosis, and chemodynamic therapy (CDT) would be a potential strategy for tumor diagnosis and enhanced treatment. However, the...
Dendrimer/metal-phenolic nanocomplexes encapsulating CuO for targeted magnetic resonance imaging and enhanced ferroptosis/cuproptosis/chemodynamic therapy by regulating the tumor microenvironment.
The combination of ferroptosis, cuproptosis, and chemodynamic therapy (CDT) would be a potential strategy for tumor diagnosis and enhanced treatment. However, the therapeutic effect was severely limited by the lack of specific delivery of catalytic ions and the low Fenton reaction efficiency in tumor microenvironment (TME) with excess glutathione, limited acidity and insufficient endogenous hydrogen peroxide. In this work, p-carboxybenzenesulfonamide (BS), a carbonic anhydrase IX (CA IX) inhibitor, was modified on the surface of generation-5 poly(amidoamine) dendrimer to load copper peroxide nanoparticles, which were complexed with iron (Fe)-tannic acid (TF) networks for targeted magnetic resonance (MR) imaging and enhanced ferroptosis/cuproptosis/CDT by regulating TME. The formed CuO@G5-BS/TF nanocomplexes with an average size of 39.4 nm could be specifically accumulated at tumor site and effectively internalized by metastatic 4T1 cells via the specific interaction between BS and CA IX over-expressed on tumor cells. Meanwhile, the inhibition of CA IX activity could not only decrease the intracellular pH to accelerate Fe/Cu release, HO self-supply and Fenton reaction, but also suppress tumor metastasis by alleviating the extracellular acidity in TME. Moreover, the reduction of Fe/Cu by intracellular glutathione (GSH) could further amplify ROS generation and enhance CDT efficacy, and the GSH depletion could in turn inhibit GPX-4 mediated antioxidant reaction to induce ferroptosis, resulting in effective therapeutic efficacy. In vivo experimental results demonstrated that CuO@G5-BS/TF could provide better tumor MR imaging, effectively inhibit the growth and metastasis of 4T1 breast tumors, and be metabolized without significant systemic toxicity. Thus, CuO@G5-BS/TF nanocomplexes provided a new approach for targeted MR imaging and enhanced ferroptosis/cuproptosis/CDT of triple-negative breast cancer. STATEMENT OF SIGNIFICANCE: Taking the advantage of dendrimer and metal-phenolic system, stable CuO@G5-BS/TF nanocomplexes with an average size of 39.4 nm were synthesized to efficiently load Fe and CuO nanoparticles for TNBC treatment and MR imaging. CuO@G5-BS/TF nanocomplexes could target tumor cells overexpressing CAIX via the specific binding with BS, and the inhibition of CAIX activity could not only decrease the intracellular pH to accelerate Fe/Cu release, HO self-supply and Fenton reaction, but also suppress tumor metastasis by alleviating the extracellular acidity. The reduction of Fe/Cu by intracellular GSH could further amplify ·OH generation, and the GSH depletion could in turn inhibit GPX-4 mediated antioxidant reaction to induce ferroptosis, resulting in effective therapeutic efficacy by enhanced ferroptosis/cuproptosis/CDT via tumor microenvironment regulation.
PubMed: 38801869
DOI: 10.1016/j.actbio.2024.05.035 -
ChemPlusChem May 2024Self-assembly of designed molecules has enabled the construction of a variety of functional nanostructures. Specifically, adaptable self-assembly has demonstrated...
Self-assembly of designed molecules has enabled the construction of a variety of functional nanostructures. Specifically, adaptable self-assembly has demonstrated several advantageous features for smart materials. Here, we demonstrate that an α-helical coiled coil conjugated with a dendrimer can adapt to spatial restriction due to the strong steric repulsion between dendrimer chains. The adaptable transformation of a tetrameric coiled coil to a trimeric coiled coil can be confirmed using analytical ultracentrifugation upon conjugation of the dendrimer to the coiled coil-forming building block. Interestingly, circular dichroism spectroscopy analysis of the dendrimer conjugate revealed an unconventional trend: the multimerization of the coiled coil is inversely dependent on concentration. This result implies that the spatial crowding between the bulky dendritic chains is significantly stronger than that between linear chains, thereby affecting the overall assembly process. We further illustrated the application potential by decorating the surface of gold nanorods (AuNRs) with the adaptable coiled coil. The dendrimer-coiled coil peptide conjugate can be utilized to fabricate organic-inorganic nanohybrids with enhanced colloidal and thermal stabilities. This study demonstrates that the coiled coil can engage in the adaptable mode of self-assembly with the potential to form dynamic peptide-based materials.
PubMed: 38797707
DOI: 10.1002/cplu.202400114 -
Polymers May 2024Cardiovascular diseases (CVDs), the world's most prominent cause of mortality, continue to be challenging conditions for patients, physicians, and researchers alike.... (Review)
Review
Cardiovascular diseases (CVDs), the world's most prominent cause of mortality, continue to be challenging conditions for patients, physicians, and researchers alike. CVDs comprise a wide range of illnesses affecting the heart, blood vessels, and the blood that flows through and between them. Advances in nanomedicine, a discipline focused on improving patient outcomes through revolutionary treatments, imaging agents, and ex vivo diagnostics, have created enthusiasm for overcoming limitations in CVDs' therapeutic and diagnostic landscapes. Nanomedicine can be involved in clinical purposes for CVD through the augmentation of cardiac or heart-related biomaterials, which can be functionally, mechanically, immunologically, and electrically improved by incorporating nanomaterials; vasculature applications, which involve systemically injected nanotherapeutics and imaging nanodiagnostics, nano-enabled biomaterials, or tissue-nanoengineered solutions; and enhancement of sensitivity and/or specificity of ex vivo diagnostic devices for patient samples. Therefore, this review discusses the latest studies based on applying organic nanoparticles in cardiovascular illness, including drug-conjugated polymers, lipid nanoparticles, and micelles. Following the revised information, it can be concluded that organic nanoparticles may be the most appropriate type of treatment for cardiovascular diseases due to their biocompatibility and capacity to integrate various drugs.
PubMed: 38794614
DOI: 10.3390/polym16101421 -
Pharmaceutics May 2024Worldwide cancer statistics have indicated about 20 million new cancer cases and over 10 million deaths in 2022 (according to data from the International Agency for... (Review)
Review
Worldwide cancer statistics have indicated about 20 million new cancer cases and over 10 million deaths in 2022 (according to data from the International Agency for Research on Cancer). One of the leading cancer treatment strategies is chemotherapy, using innovative drug delivery systems (DDSs). Self-immolative domino dendrimers (SIDendr) for triggered anti-cancer drugs appear to be a promising type of DDSs. The present review provides an up-to-date survey on the contemporary advancements in the field of SIDendr-based anti-cancer drug delivery systems (SIDendr-ac-DDSs) through an exhaustive analysis of the discovery and application of these materials in improving the pharmacological effectiveness of both novel and old drugs. In addition, this article discusses the designing, chemical structure, and targeting techniques, as well as the properties, of several SIDendr-based DDSs. Approaches for this type of targeted DDSs for anti-cancer drug release under a range of stimuli are also explored.
PubMed: 38794329
DOI: 10.3390/pharmaceutics16050668 -
Biological Response Following the Systemic Injection of PEG-PAMAM-Rhodamine Conjugates in Zebrafish.Pharmaceutics Apr 2024Numerous therapeutic and diagnostic approaches used within a clinical setting depend on the administration of compounds via systemic delivery. Biomaterials at the...
Numerous therapeutic and diagnostic approaches used within a clinical setting depend on the administration of compounds via systemic delivery. Biomaterials at the nanometer scale, as dendrimers, act as delivery systems by improving cargo bioavailability, circulation time, and the targeting of specific tissues. Although evaluating the efficacy of pharmacological agents based on nanobiomaterials is crucial, conducting toxicological assessments of biomaterials is essential for advancing clinical translation. Here, a zebrafish larvae model was explored to assess the biocompatibility of poly(amido amine) (PAMAM), one of the most exploited dendrimers for drug delivery. We report the impact of a systemic injection of polyethylene glycol (PEG)-modified G4 PAMAM conjugated with rhodamine (Rho) as a mimetic drug (PEG-PAMAM-Rho) on survival, animal development, inflammation, and neurotoxicity. A concentration- and time-dependent effect was observed on mortality, developmental morphology, and innate immune system activation (macrophages). Significant effects in toxicological indicators were reported in the highest tested concentration (50 mg/mL PEG-PAMAM-Rho) as early as 48 h post-injection. Additionally, a lower concentration of PEG-PAMAM-Rho (5 mg/mL) was found to be safe and subsequently tested for neurotoxicity through behavioral assays. In accordance, no significative signs of toxicity were detected. In conclusion, the dose response of the animal was assessed, and the safe dosage for future use in theragnostics was defined. Additionally, new methodologies were established that can be adapted to further studies in toxicology using other nanosystems for systemic delivery.
PubMed: 38794270
DOI: 10.3390/pharmaceutics16050608 -
Microorganisms May 2024Conjugation of carbohydrates to nanomaterials has been extensively studied and recognized as an alternative in the biomedical field. Dendrimers synthesized with mannose...
Conjugation of carbohydrates to nanomaterials has been extensively studied and recognized as an alternative in the biomedical field. Dendrimers synthesized with mannose at the end group and with entrapped zero-valent copper/silver could be a potential candidate against bacterial proliferation. This study is aimed at investigating the bactericidal activity of metal-glycodendrimers. The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction was used to synthesize a new mannosylated dendrimer containing 12 mannopyranoside residues in the periphery. The enterotoxigenic fimbriae 4 (ETEC:F4) viability, measured at 600 nm, showed the half-inhibitory concentration (IC) of metal-free glycodendrimers (D), copper-loaded glycodendrimers (D:Cu) and silver-loaded glycodendrimers (D:Ag) closed to 4.5 × 10, 3.5 × 10 and to 1.0 × 10 µg/mL, respectively, and minimum inhibitory concentration (MIC) of D, D:Cu and D:Ag of 2.0, 1.5 and 1.0 × 10 µg/mL, respectively. The release of bacteria contents onto broth and the inhibition of ETEC:F4 biofilm formation increased with the number of metallo-glycodendrimer materials, with a special interest in silver-containing nanomaterial, which had the highest activity, suggesting that glycodendrimer-based materials interfered with bacteria-bacteria or bacteria-polystyrene interactions, with bacteria metabolism and can disrupt bacteria cell walls. Our findings identify metal-mannose-dendrimers as potent bactericidal agents and emphasize the effect of entrapped zero-valent metal against ETEC:F4.
PubMed: 38792795
DOI: 10.3390/microorganisms12050966 -
Molecules (Basel, Switzerland) May 2024The eye's complex anatomical structures present formidable barriers to effective drug delivery across a range of ocular diseases, from anterior to posterior segment... (Review)
Review
The eye's complex anatomical structures present formidable barriers to effective drug delivery across a range of ocular diseases, from anterior to posterior segment pathologies. Emerging as a promising solution to these challenges, nanotechnology-based platforms-including but not limited to liposomes, dendrimers, and micelles-have shown the potential to revolutionize ophthalmic therapeutics. These nanocarriers enhance drug bioavailability, increase residence time in targeted ocular tissues, and offer precise, localized delivery, minimizing systemic side effects. Focusing on pediatric ophthalmology, particularly on retinoblastoma, this review delves into the recent advancements in functionalized nanosystems for drug delivery. Covering the literature from 2017 to 2023, it comprehensively examines these nanocarriers' potential impact on transforming the treatment landscape for retinoblastoma. The review highlights the critical role of these platforms in overcoming the unique pediatric eye barriers, thus enhancing treatment efficacy. It underscores the necessity for ongoing research to realize the full clinical potential of these innovative drug delivery systems in pediatric ophthalmology.
Topics: Retinoblastoma; Humans; Drug Delivery Systems; Drug Carriers; Child; Nanoparticles; Micelles; Liposomes; Dendrimers; Retinal Neoplasms; Administration, Ophthalmic; Nanotechnology
PubMed: 38792122
DOI: 10.3390/molecules29102263 -
Gels (Basel, Switzerland) Apr 2024This work reports on a novel family of silver metallogels based on discrete coordination complexes. Structurally, they consist of dendrimers containing a trinuclear...
This work reports on a novel family of silver metallogels based on discrete coordination complexes. Structurally, they consist of dendrimers containing a trinuclear silver metallacycle at the core, with the general formula [M(μ-pz)], and poly(benzyl)ether branched structures with different numbers or terminal alkoxy chains at the periphery. These silver metallodendrimers are able to gel low-polarity solvents such as dodecane or cyclohexane, giving rise to luminescent organogels at room temperature with the property of aggregation-induced emission (AIE). This property means that in solution or the sol state, they are weak emitters, but in the gel state, luminescence is considerably increased. In this particular case, they exhibit blue luminescence. Two different dendritic scaffolds have been studied, finding significant differences in solubility, gel formation and dependence of luminescence on temperature. The results show that properly tailored silver gelators can show luminescence in the gel state.
PubMed: 38786209
DOI: 10.3390/gels10050291 -
International Journal of Pharmaceutics Jun 2024Blindness in the elderly is often caused by age-related macular degeneration (AMD). The advanced type of AMD known as neovascular AMD (nAMD) has been linked to being the... (Review)
Review
Blindness in the elderly is often caused by age-related macular degeneration (AMD). The advanced type of AMD known as neovascular AMD (nAMD) has been linked to being the predominant cause of visual impairment in these people. Multiple neovascular structures including choroidal neovascular (CNV) membranes, fluid exudation, hemorrhages, and subretinal fibrosis, are diagnostic of nAMD. These pathological alterations ultimately lead to anatomical and visual loss. It is known that vascular endothelial growth factor (VEGF), a type of proangiogenic factor, mediates the pathological process underlying nAMD. Therefore, various therapies have evolved to directly target the disease. In this review article, an attempt has been made to discuss general explanations about this disease, all common treatment methods based on anti-VEGF drugs, and the use of drug delivery systems in the treatment of AMD. Initially, the pathophysiology, angiogenesis, and different types of AMD were described. Then we described current treatments and future treatment prospects for AMD and outlined the advantages and disadvantages of each. In this context, we first examined the types of therapeutic biomolecules and anti-VEGF drugs that are used in the treatment of AMD. These biomolecules include aptamers, monoclonal antibodies, small interfering RNAs, microRNAs, peptides, fusion proteins, nanobodies, and other therapeutic biomolecules. Finally, we described drug delivery systems based on liposomes, nanomicelles, nanoemulsions, nanoparticles, cyclodextrin, dendrimers, and composite vehicles that are used in AMD therapy.
Topics: Humans; Drug Delivery Systems; Macular Degeneration; Angiogenesis Inhibitors; Animals; Vascular Endothelial Growth Factor A; Choroidal Neovascularization
PubMed: 38782152
DOI: 10.1016/j.ijpharm.2024.124258