Silicasomes in Oncology: From Conventional Chemotherapy to Combined Immunotherapy.

The use of nanoparticles as drug carriers in oncology has evolved from their traditional role as chemotherapy carriers to their application in immunotherapy, exploiting not only their passive accumulation in solid tumors but also their ability to interact with immune cells. Silicasomes are highly versatile nanoplatforms composed of a mesoporous silica core whose external surface is coated with a lipid bilayer that allows the co-delivery of therapeutic agents having different chemical natures (small molecules, proteins, enzymes, or oligonucleotides, among others). Herein, cutting-edge advances carried out in the development and application of silicasomes are presented, providing a general description of the performance of these nanotransporters.

Liposomal-Based Nanoarchitectonics as Bispecific T Cell Engagers in Neuroblastoma Therapy.

Neuroblastoma (NB) is an aggressive pediatric solid tumor that lacks efficient treatment. In the past few years, the use of engineered lymphocytes endowed with chimeric antigen receptors (CAR T), which improve their natural skills against tumoral cells, has provided a highly valuable strategy to eradicate tumors in a specific and safe manner. Unfortunately, despite the excellent results achieved by these cell-based therapies in liquid tumors, their efficacy in the treatment of solid malignancies is usually modest due to the existence of several biological barriers which compromise their efficacy.

Recent Advances on the Catalytic Asymmetric Allylic α-Alkylation of Carbonyl Derivatives Using Free Allylic Alcohols.

During the last years, the development of more sustainable and straightforward methodologies to minimize the generation of waste organic substances has acquired high importance within synthetic organic chemistry. Therefore, it is not surprising that many efforts are devoted to ameliorating already well-known successful methodologies, that is, the case of the asymmetric allylic allylation reaction of carbonyl compounds. The use of free alcohols as alkylating agents in this transformation represents a step forward in this sense since it minimizes waste production and the substrate manipulation.

Boron-Catalyzed, Diastereo- and Enantioselective Allylation of Ketones with Allenes.

The diastereo- and enantioselective allylation of ketones remains a synthetic challenge, with transition metal catalysis offering the most applied methods. Here, a boron-catalyzed allylation of ketones with allenes is presented. Excellent yield, regioselectivity, and diastereoselectivity were found across functionalized substrates.

Diastereoselective, Catalytic Access to Cross-Aldol Products Directly from Esters and Lactones.

High oxidation-state carbonyl coupling partners including esters and lactones were reacted with enones to give aldol-type products directly using two-fold organoborane catalysis. This new retrosynthetic disconnection to aldol-type products is compatible with enolisable coupling partners, without self-condensation, and couples the high reactivity of secondary dialkylboranes with the stability of pinacolboronic esters. Excellent chemoselectivity, substrate scope (including those containing reducible functionalities and free alcohols) and diastereocontrol were achieved to access both the syn- and anti-aldol-type products.

Nanomaterials and Nanostructures Hand-In-Hand with Biology.

The nanoparticle's synthesis had its tipping point at the beginning of the 21st century, opening up the possibility of manufacturing nanoparticles with almost every imaginable shape and size [...

Strategies for the Biofunctionalization of Straining Flow Spinning Regenerated Fibers.

High-performance regenerated silkworm () silk fibers can be produced efficiently through the straining flow spinning (SFS) technique. In addition to an enhanced biocompatibility that results from the removal of contaminants during the processing of the material, regenerated silk fibers may be functionalized conveniently by using a range of different strategies. In this work, the possibility of implementing various functionalization techniques is explored, including the production of fluorescent fibers that may be tracked when implanted, the combination of the fibers with enzymes to yield fibers with catalytic properties, and the functionalization of the fibers with cell-adhesion motifs to modulate the adherence of different cell lineages to the material.

Bacteria as Nanoparticle Carriers for Immunotherapy in Oncology.

The use of nanocarriers to deliver antitumor agents to solid tumors must overcome biological barriers in order to provide effective clinical responses. Once within the tumor, a nanocarrier should navigate into a dense extracellular matrix, overcoming intratumoral pressure to push it out of the diseased tissue. In recent years, a paradigm change has been proposed, shifting the target of nanomedicine from the tumoral cells to the immune system, in order to exploit the natural ability of this system to capture and interact with nanometric moieties.

Janus-Type Mesoporous Silica Nanoparticles for Sequential Tumoral Cell and Mitochondria Targeting.

The development of nanoparticles has provided a powerful weapon in the fight against cancer due to the discovery of their selective accumulation in tumoral tissues, known as enhanced permeation and retention (EPR) effect (Peer et al, Nat Nanotechnol 2:751-760, 2007). Tumoral tissues require afastformation of blood vessels to sustain this rapid growth.

UVA-Degradable Collagenase Nanocapsules as a Potential Treatment for Fibrotic Diseases.

Peyronie and Dupuytren are pathologies characterized by the appearance of localized fibrotic lesions in an organ. These disorders originate from an excessive production of collagen in the tissue provoking dysfunction and functional limitations to the patients. Local administration of collagenase is the most used treatment for these fibrotic-type diseases, but a high lability of the enzyme limits its therapeutic efficacy.

Evaluation of the penetration process of fluorescent collagenase nanocapsules in a 3D collagen gel.

One of the major limitations of nanomedicine is the scarce penetration of nanoparticles in tumoral tissues. These constrains have been tried to be solved by different strategies, such as the employ of polyethyleneglycol (PEG) to avoid the opsonization or reducing the extracellular matrix (ECM) density. Our research group has developed some strategies to overcome these limitations such as the employ of pH-sensitive collagenase nanocapsules for the digestion of the collagen-rich extracellular matrix present in most of tumoral tissues.

Bacteria as Nanoparticles Carrier for Enhancing Penetration in a Tumoral Matrix Model.

One of the major concerns in the application of nanocarriers in oncology is their scarce penetration capacity in tumoral tissues, which drastically compromises the effctivity. Living organisms as cells and bacteria present the capacity to navigate autonomously following chemical gradients being able to penetrate deeply into dense tissues. In the recent years, the possibility to employ these organisms for the transportation of therapeutic agents and nanocarriers attached on their membrane or engulfed in their inner space have received huge attention.

Mesoporous Silica Nanoparticles as Theranostic Antitumoral Nanomedicines.

Nanoparticles have become a powerful tool in oncology not only as carrier of the highly toxic chemotherapeutic drugs but also as imaging contrast agents that provide valuable information about the state of the disease and its progression. The enhanced permeation and retention effect for loaded nanocarriers in tumors allow substantial improvement of selectivity and safety of anticancer nanomedicines. Additionally, the possibility to design stimuli-responsive nanocarriers able to release their payload in response to specific stimuli provide an excellent control on the administered dosage.

Direct Synthesis of -Disubstituted Formamides by Oxidation of Imines Using an HFIP/UHP System.

The straightforward synthesis of -disubstituted formamides using a combination of 1,1,1,3,3,3-hexafluoroispropanol (HFIP) and HO is described. The unique features of HFIP allowed the utilization of a green oxidant such as HO, and the products, arising from an oxidation-rearrangement sequence, were obtained in good to high yields under smooth reaction conditions.

HFIP-Promoted Synthesis of Substituted Tetrahydrofurans by Reaction of Epoxides with Electron-Rich Alkenes.

In the present work, the employment of fluorinated alcohols, specifically 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), as solvent and promoter of the catalyst-free synthesis of substituted tetrahydrofuranes through the addition of electron-rich alkenes to epoxydes is described. The unique properties of this fluorinated alcohol, which is very different from their non-fluorinated analogs, allows carrying out this new straightforward protocol under smooth reaction conditions affording the corresponding adducts in moderate yields in the majority of cases. Remarkably, this methodology has allowed the synthesis of new tetrahydrofuran-based spiro compounds as well as tetrahydrofurobenzofuran derivatives.

Inorganic Porous Nanoparticles for Drug Delivery in Antitumoral Therapy.

The use of nanoparticles in oncology to deliver chemotherapeutic agents has received considerable attention in the last decades due to their tendency to be passively accumulated in solid tumors. Besides this remarkable property, the surface of these nanocarriers can be decorated with targeting moieties capable to recognize malignant cells which lead to selective nanoparticle uptake mainly in the diseased cells, without affecting the healthy ones. Among the different nanocarriers which have been developed with this purpose, inorganic porous nanomaterials constitute some of the most interesting due to their unique properties such as excellent cargo capacity, high biocompatibility and chemical, thermal and mechanical robustness, among others.

Oxidation of Electron-Rich Arenes Using HFIP-UHP System.

The straightforward oxidation of electron-rich arenes, namely, phenols, naphthols, and anisole derivatives, under mild reaction conditions, is described by means of the use of an environmentally benign HFIP-UHP system. The corresponding quinones or hydroxylated arenes were obtained in moderate to good yields.

Tumor Targeted Nanocarriers for Immunotherapy.

The paramount discovery of passive accumulation of nanoparticles in tumoral tissues triggered the development of a wide number of different nanoparticles capable of transporting therapeutic agents to tumoral tissues in a controlled and selective way. These nanocarriers have been endowed with important capacities such as stimuli-responsive properties, targeting abilities, or the capacity to be monitored by imaging techniques. However, after decades of intense research efforts, only a few nanomedicines have reached the market.

Overcoming the stability, toxicity, and biodegradation challenges of tumor stimuli-responsive inorganic nanoparticles for delivery of cancer therapeutics.

: Stimuli-responsive nanomaterials for cancer therapy have attracted much interest recently due to their potential for improving the current standard of care. Different types of inorganic nanoparticles are widely employed for the development of these strategies, but in some cases safety concerns hinder their clinical translation. This review aims to provide an overview of the challenges that inorganic nanoparticles face regarding their stability, toxicity, and biodegradability, as well as the strategies that have been proposed to overcome them.

Targeting strategies for improving the efficacy of nanomedicine in oncology.

The use of nanoparticles as drug carriers has provided a powerful weapon in the fight against cancer. These nanocarriers are able to transport drugs that exhibit very different nature such as lipophilic or hydrophilic drugs and big macromolecules as proteins or RNA. Moreover, the external surface of these carriers can be decorated with different moieties with high affinity for specific membrane receptors of the tumoral cells to direct their action specifically to the malignant cells.

Molecular Scaffolds as Double-Targeting Agents For the Diagnosis and Treatment of Neuroblastoma.

The selective delivery of therapeutic and imaging agents to tumoral cells has been postulated as one of the most important challenges in the nanomedicine field. Meta-iodobenzilguanidine (MIBG) is widely used for the diagnosis of neuroblastoma (NB) due to its strong affinity for the norepinephrine transporter (NET), usually overexpressed on the membrane of malignant cells. Herein, a family of novel Y-shaped scaffolds has been synthesized, which have structural analogues of MIBG covalently attached at each end of the Y-structure.

Stereogenic Centers.

The demand for chiral organic entities for different industrial purposes has grown exponentially in the last decades. [..

Controlled Release With Emphasis on Ultrasound-Induced Release.

Mesoporous silica nanoparticles (MSNs) represent a promising approach to be used as nanocarriers because they fulfill some basic criteria: biocompatibility, high loading capacity and possibility of easy surface modifications. As a consequence, MSNs have been employed to design sophisticated stimuli-responsive nanocarriers able to release the entrapped cargo on demand. Among those stimuli ultrasound (US) is considered as one of the most promising triggers for drug delivery systems due to the high tissue-penetrating capability and non-invasiveness.

Chiral 2-Aminobenzimidazole as Bifunctional Catalyst in the Asymmetric Electrophilic Amination of Unprotected 3-Substituted Oxindoles.

The use of readily available chiral -cyclohexanediamine-benzimidazole derivatives as bifunctional organocatalysts in the asymmetric electrophilic amination of unprotected 3-substituted oxindoles is presented. Different organocatalysts were evaluated; the most successful one contained a dimethylamino moiety (). With this catalyst under optimized conditions, different oxindoles containing a wide variety of substituents at the 3-position were aminated in good yields and with good to excellent enantioselectivities using di--butylazodicarboxylate as the aminating agent.