Insights into Targeted and Stimulus-Responsive Nanocarriers for Brain Cancer Treatment.

Brain cancers, especially glioblastoma multiforme, are associated with poor prognosis due to the limited efficacy of current therapies. Nanomedicine has emerged as a versatile technology to treat various diseases, including cancers, and has played an indispensable role in combatting the COVID-19 pandemic as evidenced by the role that lipid nanocarrier-based vaccines have played. The tunability of nanocarrier physicochemical properties -including size, shape, surface chemistry, and drug release kinetics- has resulted in the development of a wide range of nanocarriers for brain cancer treatment. These nanocarriers can improve the pharmacokinetics of drugs, increase blood-brain barrier transfer efficiency, and specifically target brain cancer cells. These unique features would potentially allow for more efficient treatment of brain cancer with fewer side effects and better therapeutic outcomes. This review provides an overview of brain cancers, current therapeutic options, and challenges to efficient brain cancer treatment. The latest advances in nanomedicine strategies are investigated with an emphasis on targeted and stimulus-responsive nanocarriers and their potential for clinical translation.

Recent Advances in Formulations for Long-Acting Delivery of Therapeutic Peptides.

Recent preclinical and clinical studies have focused on the active area of therapeutic peptides due to their high potency, selectivity, and specificity in treating a broad range of diseases. However, therapeutic peptides suffer from multiple disadvantages, such as limited oral bioavailability, short half-life, rapid clearance from the body, and susceptibility to physiological conditions (e.g., acidic pH and enzymolysis). Therefore, high peptide dosages and dose frequencies are required for effective patient treatment. Recent innovations in pharmaceutical formulations have substantially improved therapeutic peptide administration by providing the following advantages: long-acting delivery, precise dose administration, retention of biological activity, and improvement of patient compliance. This review discusses therapeutic peptides and challenges in their delivery and explores recent peptide delivery formulations, including micro/nanoparticles (based on lipids, polymers, porous silicon, silica, and stimuli-responsive materials), (stimuli-responsive) hydrogels, particle/hydrogel composites, and (natural or synthetic) scaffolds. This review further covers the applications of these formulations for prolonged delivery and sustained release of therapeutic peptides and their impact on peptide bioactivity, loading efficiency, and (in vitro/in vivo) release parameters.

Polymer-functionalization of carbon nanotube by in situ conventional and controlled radical polymerizations.

Functionalization of carbon nanotube (CNT) with polymers has drawn much attention due to its wide range of applications. Polymer-functionalized CNT could exhibit variety of properties, such as responsivity to environmental stimuli, ability of complexation with metal ions, increased dispersibility in different solvents, higher compatibility with polymer matrix, etc. Chemical and physical methods have been developed for the preparation of polymer-functionalized CNT. Polymer chains are chemically bonded to the CNT edge or surface in the chemical methods, which results in highly stable CNT/polymer composites. "Grafting to", "grafting from", and "grafting through" methods are the most common chemical methods for polymer-functionalization of CNT. In "grafting to" method, pre-fabricated polymer chains are coupled with the either functionalized or non-functionalized CNT. In "grafting from" and "grafting through" methods, CNT is functionalized by polymers simultaneously synthesized by in situ polymerization methods. Conventional free radical polymerization (FRP) and also controlled radical polymerization (CRP) are the most promising methods for in situ tethering of polymer brushes onto the surface of CNT due to their control over the grafting density, thickness, and functionality of the polymer brushes. The main focus of this review is on the synthesis of polymer-functionalized CNT via both the "grafting from" and "grafting through" methods on the basis of FRP and CRP routs, which is commonly known as in situ polymerizations. Finally, the most important challenges and applications of the in situ polymer grafting methods are discussed, which could be interesting for the future works.

Functionalization of carbon nanotubes by combination of controlled radical polymerization and "grafting to" method.

This paper reviews the recent advances in non-covalent and covalent tethering of small molecules and polymer chains onto carbon nanotube (CNT) and its derivatives. The functionalized CNT has recently attracted great attention because of an increasing number of its potential applications. In non-covalent functionalization of CNT, the sp2-hybridized network plays a crucial role. The non-covalent grafting of small molecules and polymers can mainly be carried out through hydrogen bonding and π-stacking interactions. In covalent functionalization of CNT, condensation, cycloaddition, and addition reactions play a key role. Polymer modification has been reported by using three main methods of "grafting from", "grafting through", and also "grafting to". The "grafting from" and "grafting through" rely on propagation of polymer chains in the presence of CNT modified with initiator and double bond moieties, respectively. In "grafting to" method, which is the main aim of this review, the pre-fabricated polymer chains are mainly grafted onto the surface using coupling reactions. The coupling reactions are used for grafting pre-fabricated polymer chains and also small molecules onto CNT. Recent studies on grafting polymer chains onto CNT via "grafting to" method have focused on the pre-fabricated polymer chains by conventional and controlled radical polymerization (CRP) methods. CRP includes reversible activation, atom transfer, degenerative (exchange) chain transfer, and reversible chain transfer mechanisms, and could result in polymer-grafted CNT with narrow polydispersity index of the grafted polymer chains. Based on the mentioned mechanisms, nitroxide-mediated polymerization, atom transfer radical polymerization, and reversible addition-fragmentation chain transfer are known as the three commonly used CRP methods. Such polymer-modified CNT has lots of applications in batteries, biomedical fields, sensors, filtration, solar cells, etc.

Synthesis of coumarin-containing multi-responsive CNC-grafted and free copolymers with application in nitrate ion removal from aqueous solutions.

Cellulose nanocrystals (CNC)-grafted and free copolymers were synthesized in three different ratios of DMAEMA and coumarin monomers (30:5, 40:7, and 50:10) through reversible addition-fragmentation chain transfer polymerization. These multi-responsive polymers to carbon dioxide (CO2), temperature, and light triggers can be used in nitrate ions removal from aqueous solutions. These amphiphilic copolymers were self-assembled to vesicular structures in water. Adsorption of nitrate ions was carried out by protonation of the CO2-responsive block with inserting of CO2. Proton nuclear magnetic resonance and thermogravimetric analysis were used to confirm the synthesis process. Responsivity to temperature, CO2, and light in addition to the adsorption of nitrate ions from aqueous solutions was studied by UV-vis spectroscopy and dynamic light scattering. By increasing the PDMAEMA content, the adsorption capacity has also increased. The CNC-grafted copolymers showed lower adsorption in comparison with the free copolymers. The CNC-grafted copolymers can be regenerated by light and filtration processes.

Polymer grafting on graphene layers by controlled radical polymerization.

In situ controlled radical polymerization (CRP) is considered as an important approach to graft polymer brushes with controlled grafting density, functionality, and thickness on graphene layers. Polymers are tethered with chain end or through its backbone to the surface or edge of graphene layers with two in situ polymerization methods of "grafting from" and "grafting through" and also a method based on coupling reactions known as "grafting to". The "grafting from" method relies on the propagation of polymer chains from the surface- or edge-attached initiators. The "grafting through" method is based on incorporation of double bond-modified graphene layers into polymer chains through the propagation reaction. The "grafting to" technique involves attachment of pre-fabricated polymer chains to the graphene substrate. Here, physical and chemical attachment approaches are also considered in polymer-modification of graphene layers. Combination of CRP mechanisms of reversible activation, degenerative (exchange) chain transfer, atom transfer, and reversible chain transfer with various kinds of grafting reactions makes it possible to selectively functionalize graphene layers. The main aim of this review is assessment of the recent advances in the field of preparation of polymer-grafted graphene substrates with well-defined polymers of controlled molecular weight, thickness, and polydispersity index. Study of the opportunities and challenges for the future works in controlling of grafting density, site-selectivity in grafting, and various topologies of the brushes with potential applications in stimuli-responsive surfaces, polymer composites, Pickering emulsions, coating technologies, and sensors is also considered.