Carolina Salvador-Morales

Immunocompatibility properties of lipid-polymer hybrid nanoparticles with heterogeneous surface functional groups

Here we report the immunological characterization of lipid-polymer hybrid nanoparticles (NPs) and propose a method to control the levels of complement activation induced by these NPs. This method consists of the highly specific modification of the NP surface with methoxyl, carboxyl, and amine groups. Hybrid NPs with methoxyl surface groups induced the lowest complement activation, whereas the NPs with amine surface groups induced the highest activation. All possible combinations among carboxyl, amine, and methoxyl groups also activated the complement system to a certain extent. All types of NPs activated the complement system primarily via the alternative pathway rather than the lectin pathway. The classical pathway was activated to a very small extent by the NPs with carboxyl and amine surface groups. Human serum and plasma protein binding studies showed that these NPs had different protein binding patterns. Studies of both complement activation and coagulation activation suggested that NPs with methoxyl surface groups might be an ideal candidate for drug delivery applications, since they are not likely to cause any immunological adverse reaction in the human body.

Emerging nanotechnology approaches for HIV/AIDS treatment and prevention

Currently, there is no cure and no preventive vaccine for HIV/AIDS. Combination antiretroviral therapy has dramatically improved treatment, but it has to be taken for a lifetime, has major side effects and is ineffective in patients in whom the virus develops resistance. Nanotechnology is an emerging multidisciplinary field that is revolutionizing medicine in the 21st century. It has a vast potential to radically advance the treatment and prevention of HIV/AIDS. In this review, we discuss the challenges with the current treatment of the disease and shed light on the remarkable potential of nanotechnology to provide more effective treatment and prevention for HIV/AIDS by advancing antiretroviral therapy, gene therapy, immunotherapy, vaccinology and microbicides.

‘Green’ derivatization of carbon nanotubes with Nylon 6 and L-alanine

Amide derivatives of L-alanine and e-caprolactam were readily obtained on diamine-functionalized oxidized single-walled and pristine multi-walled carbon nanotubes through a one-step direct amidation reaction, which employs thermal activation at 160–200 °C instead of chemical activation, avoids the use of organic solvents, and requires a few hours only for completion. In the case of e-caprolactam, amino groups attached to the nanotubes initiated polymerization into Nylon 6. The functionalized nanotubes were characterized by infrared and Raman spectroscopy, scanning and transmission electron microscopy, atomic force microscopy, thermal gravimetric analysis and differential scanning calorimetry.

Multifunctional nanoparticles for prostate cancer therapy

Multifunctional nanoparticles promise significantly better treatment for prostate cancer. This review begins with a molecular and physiological overview of prostate cancer, including current treatments in various stages of disease development. Emerging nanoparticle technology in chemotherapy, hyperthermia therapy and gene therapy will be discussed. We highlight novel advances in nanoparticle technology for prostate cancer and indicate future challenges in the rational design of multifunctional nanoparticles, such as understanding tumor characteristics and the activation of the complement system.

Recent developments in multifunctional hybrid nanoparticles: opportunities and challenges in cancer therapy

Multifunctional hybrid nanoparticles combine some of the unique physical and chemical characteristics of two or more classes of materials, such as polymers, liposomes, metals, quantum dots and mesoporous silica among others, to create a versatile and robust new class of nanoparticles. Here we discuss the most recent synthetic strategies to create these hybrid systems and analyze four key design aspects: stability, encapsulation of therapeutic and imaging agents, controlled release of encapsulated agents, and biocompatibility. Through the combination of multiple nanomaterials, hybrid nanoparticles aim to expand the functionality of single-component systems, using the strengths of one material to improve on weaknesses of another. We then examine how hybrid nanoparticle platforms provide unique opportunities in cancer therapy, specifically in the treatment of multidrug resistant cancer. Finally, we discuss some of the challenges hybrid nanoparticles systems might face in their large scale synthesis and commercialization in the biopharmaceutical industry.

Closing the gap: accelerating the translational process in nanomedicine by proposing standardized characterization techniques

On the cusp of widespread permeation of nanomedicine, academia, industry, and government have invested substantial financial resources in developing new ways to better treat diseases. Materials have unique physical and chemical properties at the nanoscale compared with their bulk or small-molecule analogs. These unique properties have been greatly advantageous in providing innovative solutions for medical treatments at the bench level. However, nanomedicine research has not yet fully permeated the clinical setting because of several limitations. Among these limitations are the lack of universal standards for characterizing nanomaterials and the limited knowledge that we possess regarding the interactions between nanomaterials and biological entities such as proteins. In this review, we report on recent developments in the characterization of nanomaterials as well as the newest information about the interactions between nanomaterials and proteins in the human body. We propose a standard set of techniques for universal characterization of nanomaterials. We also address relevant regulatory issues involved in the translational process for the development of drug molecules and drug delivery systems. Adherence and refinement of a universal standard in nanomaterial characterization as well as the acquisition of a deeper understanding of nanomaterials and proteins will likely accelerate the use of nanomedicine in common practice to a great extent.

Spontaneous Formation of Heterogeneous Patches on Polymer–Lipid Core–Shell Particle Surfaces during Self‐Assembly

Spontaneous formation of heterogeneous patches on the surface of lipid-based nanoparticles (NPs) and microparticles (MPs) due to the segregation of two different functional groups. Patch formation is observed when tracing the functional groups with quantum dots, gold nanoparticles, and fluorescent dyes. This discovery could have important implications for the future design of self-assembled NPs and MPs for different biomedical applications.

Recognition of Carbon Nanotubes by the Human Innate Immune System

A major function of the human innate immune system is to recognize non-self: i.e., invading microorganisms or altered, damaged self macromolecules and cells. Various components of the human immune system recognize foreign synthetic materials, including carbon nanotubes (CNTs). The complement system proteins in blood, and the collectins, SP-A and SP-D in the lungs bind to carbon nanotubes, in competition with other plasma proteins, and may influence their subsequent adhesion to and uptake by cells and their localization in the body. Modification of the surface chemistry of carbon nanotubes alters their binding to complement proteins and collectins, and provides information on the mechanism by which binding of these proteins occurs.

Altered mitochondrial dynamics as a consequence of Venezuelan Equine encephalitis virus infection

ABSTRACT Mitochondria are sentinel organelles that are impacted by various forms of cellular stress, including viral infections. While signaling events associated with mitochondria, including those activated by pathogen associated molecular patterns (PAMPs), are widely studied, alterations in mitochondrial distribution and changes in mitochondrial dynamics are also beginning to be associated with cellular insult. Cells of neuronal origin have been demonstrated to display remarkable alterations in several instances, including neurodegenerative disorders. Venezuelan Equine Encephalitis Virus (VEEV) is a New World alphavirus that infects neuronal cells and contributes to an encephalitic phenotype. We demonstrate that upon infection by the vaccine strain of VEEV (TC-83), astrocytoma cells experience a robust drop in mitochondrial activity, which corresponds with an increased accumulation of reactive oxygen species (ROS) in an infection-dependent manner. Infection status also corresponds with a prominent perinuclear accumulation of mitochondria. Cellular enzymatic machinery, including PINK1 and Parkin, appears to be enriched in mitochondrial fractions as compared with uninfected cells, which is indicative of mitochondrial damage. Dynamin related protein 1 (Drp1), a protein that is associated with mitochondrial fission, demonstrated a modest enrichment in mitochondrial fractions of infected cells. Treatment with an inhibitor of mitochondrial fission, Mdivi-1, led to a decrease in caspase cleavage, suggesting that mitochondrial fission was likely to contribute to apoptosis of infected cells. Finally, our data demonstrate that mitophagy ensues in infected cells. In combination, our data suggest that VEEV infection results in significant changes in the mitochondrial landscape that may influence pathological outcomes in the infected cell.

Antiplatelet effect of differentially charged PEGylated lipid-polymer nanoparticles

PEGylated nanoparticles have been extensively investigated in different platforms for drug delivery. However, the physiological effects related to platelet activation, and the potential procoagulant activity which could lead to thrombosis and further cardiovascular diseases have not been widely examined. In this work, we studied the effect of differentially charged PEGylated lipid-polymer nanoparticles in the human platelet aggregation and activation by light transmission aggregometry and flow cytometry. PEGylated nanoparticles inhibited the platelet aggregation with a dose dependency (350, 700, and 1400μg/mL) in both ADP- and collagen-induced platelet aggregation, and P-selectin expression. Charged nanoparticles (anionic and cationic) presented higher inhibitions of the platelet aggregation compared to neutral nanoparticles, and particularly the cationic particles generated a slightly higher effect. The obtained results demonstrated the safety of the differentially charged PEGylated lipid-polymer nanoparticles, and their ability to inhibit the aggregation and activation of human platelets stimulated by two classic platelet activators.