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- Recent therapeutic applications of the theranostic principle with dendrimers in oncologyPublication . Mignani, Serge; Rodrigues, João; Tomás, Helena; Caminade, Anne-marie; Laurent, Régis; Shi, Xiangyang; Majoral, Jean-PierreAt the intersection between treatment and diagnosis,nanoparticlestechnologiesarestronglyimpactingthe development of both therapeutic and diagnostic agents. Consequently, the development of novel modalities for concomitant noninvasive therapy and diagnostics known as theranostics as a single platform has gained significant interests. These multifunctional theranostic platforms include carbon-based nanomaterials (e.g., carbon nanotubes), drug conjugates, aliphatic polymers, micelles, vesicles, core-shell nanoparticles,microbubblesanddendrimersbearingdifferent contrastagentsanddrugs,suchascytotoxiccompoundsinthe oncology domain. Dendrimers emerged as a new class of highly tunable hyperbranched polymers, and have been developed as useful theranostic platforms. Magnetic resonance imaging, gamma scintigraphy, computed tomography and optical imaging are the main techniques developed with dendrimers in the theranostic domain in oncology. Different imaging agents have been used such as Gd(III), 19F, Fe2O3 (MRI), 76Br (PET), 111In, 88Y, 153Gd, 188Re, 131I (SPECT), 177Lu, gold (CT) and boronated groups, siliconnaphthalocyanines, dialkylcarbocyanines and QDs (optical imaging dyes).
- Engineered non-invasive functionalized dendrimer/dendron-entrapped/complexed gold nanoparticles as a novel class of theranostic (radio)pharmaceuticals in cancer therapyPublication . Mignani, Serge; Shi, Xiangyang; Ceña, Valentin; Rodrigues, João; Tomás, Helena; Majoral, Jean-PierreNanomedicine represents a very significant contribution in current cancer treatment; in addition to surgical intervention, radiation and chemotherapeutic agents that unfortunately also kill healthy cells, inducing highly deleterious and often life-threatening side effects in the patient. Of the numerous nanoparticles used against cancer, gold nanoparticles had been developed for therapeutic applications. Inter alia, a large variety of den drimers, i.e. soft artificial macromolecules, have turned up as non-viral functional nanocarriers for entrapping drugs, imaging agents, and targeting molecules. This review will provide insights into the design, synthesis, functionalization, and development in biomedicine of engineered functionalized hybrid dendrimer-tangled gold nanoparticles in the domain of cancer theranostic. Several aspects are highlighted and discussed such as 1) dendrimer-entrapped gold(0) hybrid nanoparticles for the targeted imaging and treatment of cancer cells, 2) dendrimer encapsulating gold(0) nanoparticles (Au DENPs) for the delivery of genes, 3) Au DENPs for drug delivery applications, 4) dendrimer encapsulating gold radioactive nanoparticles for radiotherapy, and 5) dendrimer/dendron-complexed gold(III) nanoparticles as technologies to take down cancer cells.
- Morpholino-functionalized phosphorus dendrimers for precision regenerative medicine: osteogenic differentiation of mesenchymal stem cellsPublication . Li, Aijun; Fan, Yu; Cao, Xueyan; Chen, Liang; Wang, Le; Alves, Carla S.; Mignani, Serge; Majoral, Jean Pierre; Tomás, Helena; Shi, XiangyangA novel bioactive macromolecule based on morpholino-functiona lized phosphorus dendrimers (generation 2, G2-Mor+ ) was devel oped for osteogenic differentiation of mesenchymal stem cells (MSCs). Interestingly, through in vitro tests, it was shown that G2- Mor+ dendrimer can strongly promote the transformation of MSCs into osteoblasts, which implies the potential application of phos phorus de medicine.
- Present drug-likeness filters in medicinal chemistry during the hit and lead optimization process: how far can they be simplified?Publication . Mignani, Serge; Rodrigues, João; Tomás, Helena; Jalal, Rachid; Singh, Parvinder Pal; Majoral, Jean-Pierre; Vishwakarma, Ram A.During the past decade, decreasing the attrition rate of drug development candidates reaching the market has become one of the major challenges in pharmaceutical research and drug development (R&D). To facilitate the decision-making process, and to increase the probability of rapidly finding and developing high-quality compounds, a variety of multiparametric guidelines, also known as rules and ligand efficiency (LE) metrics, have been developed. However, what are the 'best' descriptors and how far can we simplify these drug-likeness prediction tools in terms of the numerous, complex properties that they relate to?
- Compound high-quality criteria: a new vision to guide the development of drugs, current situationPublication . Mignani, Serge; Huber, Scot; Tomás, Helena; Rodrigues, João; Majoral, Jean-PierreFor several decades, the pharmaceutical industry has suffered due to major issues such as reductions of the number of FDA approved drugs and biologics. Several analyses have been highlighted that the 'druglikeness' is one of the strategies to improve succeed rates of screening such as, for instance, high-throughput screening (HTS), and then hits (as starting point), leads and clinical candidates. It is clear that the improvement of compound quality accelerates the drug discovery projects. The monitoring of several indices to avoid 'molecular obesity' (ADMET problems) of final drugs from good-quality 'low-fat' starting points represents today a powerful strategy of optimization process. The development of the new guides to find drugs highlighting attempts at improving the attrition rate from hits to final medicines by focusing on how to improve the druggability of hits, leads and drugs during the drug discovery process represents a key approach to design next better generation of medicines.
- Dendrimers in combination with natural products and analogues as anti-cancer agentsPublication . Mignani, Serge; Rodrigues, João; Tomás, Helena; Zablocka, Maria; Shi, Xiangyang; Caminade, Anne-marie; Majoral, Jean-PierreFor the first time, an overview of dendrimers in combination with natural products and analogues as anti-cancer agents is presented. This reflects the development of drug delivery systems, such as dendrimers, to tackle cancers. The most significant advantages of using dendrimers in nanomedicine are their high biocompatibility, good water solubility, and their entry - with or without encapsulated, complexed or conjugated drugs - through an endocytosis process. This strategy has accelerated over the years in order to develop nanosystems as nanocarriers, to decrease the intrinsic toxicity of anti-cancer agents, to decrease the drug side effects, to increase the efficacy of the treatment, and consequently to improve patient compliance.
- A glance over doxorubicin based-nanotherapeutics: from proof-of-concept studies to solutions in the marketPublication . Gonçalves, Mara; Mignani, Serge; Rodrigues, João; Tomás, HelenaCancer is one of the leading causes of death worldwide and, as such, efforts are being done to find new che motherapeutic drugs or, alternatively, novel approaches for the delivery of old ones. In this scope, when used as vehicles for drugs, nanomaterials may potentially maximize the efficacy of the treatment and reduce its side effects, for example by a change in drug's pharmacokinetics, cell targeting and/or specific stimuli-responsive ness. This is the case of doxorubicin (DOX) that presents a broad spectrum of activity and is one of the most widely used chemotherapeutic drugs as first-line treatment. Indeed, DOX is a very interesting example of a drug for which several nanosized delivery systems have been developed over the years. While it is true that some of these systems are already in the market, it is also true that research on this subject remains very active and that there is a continuing search for new solutions. In this sense, this review takes the example of doxorubicin, not so much with the focus on the drug itself, but rather as a case study around which very diverse and imaginative nanotechnology approaches have emerged.
- Bench-to-bedside translation of dendrimers: reality or utopia? A concise analysisPublication . Mignani, Serge; Rodrigues, João; Tomás, Helena; Roy, René; Shi, Xiangyang; Majoral, Jean-PierreNanomedicine, which is an application of nanotechnologies in healthcare is developed to improve the treatments and lives of patients suffering from a range of disorders and to increase the successes of drug candidates. Within the nanotechnology universe, the remarkable unique and tunable properties of dendrimers have made them promising tools for diverse biomedical applications such as drug delivery, gene therapy and diagnostic. Up-to-date, very few dendrimers has yet gained regulatory approval for systemic administration, why? In this critical review, we briefly focus on the list of desired basic dendrimer requirements for decision-making purpose by the scientists (go/no-go decision), in early development stages, to become clinical candidates, and to move towards Investigational New Drugs (IND) application submission. In addition, the successful translation between research and clinic should be performed by the implementation of a simple roadmap to jump the 'valley of death' successfully.