Explore the vast range of titles available.

In the original publication [...]

Dendrimers constitute a distinctive category of synthetic materials that bear resemblance to proteins in various aspects, such as discrete structural organization, globular morphology, and nanoscale dimensions. Remarkably, these attributes coexist with the capacity for facile large-scale production. Due to these advantages, the realm of dendrimers has undergone substantial advancement since their inception in the 1980s. Numerous reviews have been dedicated to elucidating this subject comprehensively, delving into the properties and applications of quintessential dendrimer varieties like PAMAM, PPI, and others. Nevertheless, the contemporary landscape of dendrimers transcends these early paradigms, witnessing the emergence of a diverse array of novel dendritic architectures in recent years. In this review, we aim to present a comprehensive panorama of the expansive domain of dendrimers. As such, our focus lies in discussing the key attributes and applications of the predominant types of dendrimers existing today. We will commence with the conventional variants and progressively delve into the more pioneering ones, including Janus, supramolecular, shape-persistent, and rotaxane dendrimers.

Biomedicine represents one of the main study areas for dendrimers, which have proven to be valuable both in diagnostics and therapy, due to their capacity for improving solubility, absorption, bioavailability and targeted distribution. Molecular cytotoxicity constitutes a limiting characteristic, especially for cationic and higher-generation dendrimers. Antineoplastic research of dendrimers has been widely developed, and several types of poly(amidoamine) and poly(propylene imine) dendrimer complexes with doxorubicin, paclitaxel, imatinib, sunitinib, cisplatin, melphalan and methotrexate have shown an improvement in comparison with the drug molecule alone. The anti-inflammatory therapy focused on dendrimer complexes of ibuprofen, indomethacin, piroxicam, ketoprofen and diflunisal. In the context of the development of antibiotic-resistant bacterial strains, dendrimer complexes of fluoroquinolones, macrolides, beta-lactamines and aminoglycosides have shown promising effects. Regarding antiviral therapy, studies have been performed to develop dendrimer conjugates with tenofovir, maraviroc, zidovudine, oseltamivir and acyclovir, among others. Furthermore, cardiovascular therapy has strongly addressed dendrimers. Employed in imaging diagnostics, dendrimers reduce the dosage required to obtain images, thus improving the efficiency of radioisotopes. Dendrimers are macromolecular structures with multiple advantages that can suffer modifications depending on the chemical nature of the drug that has to be transported. The results obtained so far encourage the pursuit of new studies.

Dendrimers are nanoscopic compounds, which are monodispersed, and they are generally considered as homogeneous. PAMAM (polyamidoamine) was introduced in 1985, by Donald A. Tomalia, as a new class of polymers, named ‘starburst polymers’. This important contribution of Professor Tomalia opened a new research field involving nanotechnological approaches. From then on, many groups have been using PAMAM for diverse applications in many areas, including biomedical applications. The possibility of either linking drugs and bioactive compounds, or entrapping them into the dendrimer frame can improve many relevant biological properties, such as bioavailability, solubility, and selectivity. Directing groups to reach selective delivery in a specific organ is one of the advanced applications of PAMAM. In this review, structural and safety aspects of PAMAM and its derivatives are discussed, and some relevant applications are briefly presented. Emphasis has been given to gene delivery and targeting drugs, as advanced delivery systems using PAMAM and an incentive for its use on neglected diseases are briefly mentioned.

Dendrimers are highly branched polymers with easily modifiable surfaces. This makes them promising structures for functionalization and also for conjugation with drugs and DNA/RNA. Their architecture, which can be controlled by different synthesis processes, allows the control of characteristics such as shape, size, charge, and solubility. Dendrimers have the ability to increase the solubility and bioavailability of hydrophobic drugs. The drugs can be entrapped in the intramolecular cavity of the dendrimers or conjugated to their functional groups at their surface. Nucleic acids usually form complexes with the positively charged surface of most cationic dendrimers and this approach has been extensively employed. The presence of functional groups in the dendrimer’s exterior also permits the addition of other moieties that can actively target certain diseases and improve delivery, for instance, with folate and antibodies, now widely used as tumor targeting strategies. Dendrimers have been investigated extensively in the medical field, and cancer treatment is one of the greatest areas where they have been most used. This review will consider the main types of dendrimer currently being explored and how they can be utilized as drug and gene carriers and functionalized to improve the delivery of cancer therapy.

Antioxidants play a crucial role in preventing oxidative damage and are therefore integral to various sectors, including healthcare, food preservation, cosmetics, and industrial applications. Their capacity to enhance overall health and improve the quality and shelf life of products in these domains underscores their significance. Two powerful antioxidant dendrimers were synthesized using D-mannitol as the core and syringaldehyde as the antioxidant-producing phenolic unit. The generation 1 (G1) dendrimer features 12 syringic units on its surface, while the generation 2 (G2) dendrimer has 24. Antioxidant capacities were assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the β-carotene bleaching assays. Based on IC50 values, the G2 (0.7 μM) and G1 (1.36 μM) dendrimers show 371- and 191-fold higher antioxidant activity, respectively, compared to the starting compound, syringaldehyde (260 μM). They are also 1251- and 647-times more effective than butylated hydroxytoluene (BHT) (880 μM). Overall, G2 is twice as potent as G1. The dendrimers also provide strong protection against β-carotene bleaching. At concentrations between 3.75 and 60 μM, G2 preserves 75% to 88% of β-carotene after 16 h at 45 °C, while G1 maintains 51% to 84%. In comparison, syringaldehyde and BHT provide significantly less protection, with ranges of 21% to 47% and 22% to 36%, respectively. Their greatly enhanced antioxidant capabilities are due to the numerous free-radical-scavenging sites created by phenolic hydroxyl groups, which have electron-donating groups at the ortho and para positions. In cell viability assays using macrophages, G1 caused a decrease in cell viability at ≥31 µM. Conversely, G2 exhibited a gradual reduction in cell viability across the concentration range of 0.1 µM to 111 µM, with viability declining from 11.1% to 96.3%, indicating that the larger G2 is more cytotoxic than the smaller G1.

The application of dendrimeric constructs in medical diagnostics and therapeutics is increasing. Dendrimers have attracted attention due to their compact, spherical three-dimensional structures with surfaces that can be modified by the attachment of various drugs, hydrophilic or hydrophobic groups, or reporter molecules. In the literature, many modified dendrimer systems with various applications have been reported, including drug and gene delivery systems, biosensors, bioimaging contrast agents, tissue engineering, and therapeutic agents. Dendrimers are used for the delivery of macromolecules, miRNAs, siRNAs, and many other various biomedical applications, and they are ideal carriers for bioactive molecules. In addition, the conjugation of dendrimers with antibodies, proteins, and peptides allows for the design of vaccines with highly specific and predictable properties, and the role of dendrimers as carrier systems for vaccine antigens is increasing. In this work, we will focus on a review of the use of dendrimers in cancer diagnostics and therapy. Dendrimer-based nanosystems for drug delivery are commonly based on polyamidoamine dendrimers (PAMAM) that can be modified with drugs and contrast agents. Moreover, dendrimers can be successfully used as conjugates that deliver several substances simultaneously. The potential to develop dendrimers with multifunctional abilities has served as an impetus for the design of new molecular platforms for medical diagnostics and therapeutics.

Photodynamic therapy (PDT) is a promising cancer treatment. However, the efficacy of photosensitizers such as rose bengal (RB) is often limited by poor delivery. Dendrimer-based nanocarriers can enhance PDT efficacy in vitro, but their in vivo safety profile remains largely uncharacterized. This study aimed to assess the systemic safety of three different dendrimer-based RB delivery systems in a healthy mouse model. BALB/c mice were randomly divided into eight groups and received weekly intraperitoneal injections of either PBS (control), free RB, or one of three carriers (phosphorus dendrimer 1cat, dendrimersome DG2, PPI G3 dendrimer) with or without RB. Body weight was monitored weekly. Blood and urine samples were collected over four weeks for comprehensive biochemical and microscopic analysis, assessing markers for liver, kidney, and muscle function. No significant changes in body weight were observed across any of the groups. Analysis of blood biochemical parameters (including ALT, AST, urea, creatinine, and LDH) and urine profiles revealed no statistically significant differences between any treatment group and the PBS control group over the four-week study period. The observed minor fluctuations in some parameters were not dose- or time-dependent and remained within normal physiological ranges. The three tested nanocarrier systems - phosphorus dendrimer 1cat, dendrimersome DG2, and PPI G3 dendrimer - and their respective rose bengal formulations are well tolerated and do not induce systemic toxicity in BALB/c mice at the tested concentrations. These findings support their safety for in vivo applications and provide a basis for future efficacy studies in tumor-bearing animal models.

Glioblastoma (GB) is a grade IV astrocytoma that maintains a poor prognosis with respect to current treatment options. Despite major advancements in the fields of surgery and chemoradiotherapy over the last few decades, the life expectancy for someone with glioblastoma remains virtually unchanged and warrants a new approach for treatment. Poly(amidoamine) (PAMAM) dendrimers are a type of nanomolecule that ranges in size (between 1 and 100 nm) and shape and can offer a new viable solution for the treatment of intracranial tumors, including glioblastoma. Their ability to deliver a variety of therapeutic cargo and penetrate the blood-brain barrier (BBB), while preserving low cytotoxicity, make them a favorable candidate for further investigation into the treatment of glioblastoma. Here, we present a systematic review of the current advancements in PAMAM dendrimer technology, including the wide spectrum of dendrimer generations formulated, surface modifications, core modifications, and conjugations developed thus far to enhance tumor specificity and tumor penetration for treatment of glioblastoma. Furthermore, we highlight the extensive variety of therapeutics capable of delivery by PAMAM dendrimers for the treatment of glioblastoma, including cytokines, peptides, drugs, siRNAs, miRNAs, and organic polyphenols. While there have been prolific results stemming from aggressive research into the field of dendrimer technology, there remains a nearly inexhaustible amount of questions that remain unanswered. Nevertheless, this technology is rapidly developing and is nearing the cusp of use for aggressive tumor treatment. To that end, we further highlight future prospects in focus as researchers continue developing more optimal vehicles for the delivery of therapeutic cargo.