Polymeric-based neoantigen nanovaccine synergizes with PD-1/PD-L1 modulators, reprogramming the melanoma microenvironment.

Programmed cell death protein 1 (PD-1) and its ligand PD-L1 are targets of immune checkpoint blockade (ICB) therapies that have shown promise in cancer treatment. However, their effectiveness is often hindered by resistance mechanisms such as poor tumor immunogenicity, T-cell exhaustion, insufficient T-cell infiltration, and an immunosuppressive tumor microenvironment (TME). Overcoming these barriers requires strategies to enhance tumor immunogenicity and modulate the TME.

Off-The-Shelf Multivalent Nanoconjugate Cancer Vaccine Rescues Host Immune Response against Melanoma.

Tumor-associated antigen-based cancer vaccines suffer from limited clinical success compared to alternative immunotherapies in melanoma, an aggressive skin cancer with an immunosuppressive tumor microenvironment. The anti-tumor potential of a multivalent nanoconjugate cancer vaccine platform - a cross-linked star-shaped polyglutamate carrier (StCl) with marked lymphotropic character conjugated with melanoma-associated peptide antigens is evaluated through redox-responsive linkers. The co-delivery of melanoma-associated peptide antigens by the nanoconjugate platform induced significant effector immune responses in a mouse melanoma model.

Better, Faster, Stronger: Accelerating mRNA-Based Immunotherapies With Nanocarriers.

Messenger ribonucleic acid (mRNA) therapeutics are attracting attention as promising tools in cancer immunotherapy due to their ability to leverage the in vivo expression of all known protein sequences. Even small amounts of mRNA can have a powerful effect on cancer vaccines by promoting the synthesis of tumor-specific antigens (TSA) or tumor-associated antigens (TAA) by antigen-presenting cells (APC). These antigens are then presented to T cells, eliciting strong antitumor immune stimulation.

Selenium Nanoparticles Synergize with a KRAS Nanovaccine against Breast Cancer.

Selenium (Se) is an element crucial for human health, known for its anticancer properties. Although selenium nanoparticles (SeNPs) have shown lower toxicity and higher biocompatibility than other Se compounds, bare SeNPs are unstable in aqueous solutions. In this study, several materials, including bovine serum albumin (BSA), chitosan, polymethyl vinyl ether-alt-maleic anhydride, and tocopherol polyethylene glycol succinate, are explored to develop stable SeNPs and further evaluate their potential as candidates for cancer treatment.

Polyoxazoline-Based Nanovaccine Synergizes with Tumor-Associated Macrophage Targeting and Anti-PD-1 Immunotherapy against Solid Tumors.

Immune checkpoint blockade reaches remarkable clinical responses. However, even in the most favorable cases, half of these patients do not benefit from these therapies in the long term. It is hypothesized that the activation of host immunity by co-delivering peptide antigens, adjuvants, and regulators of the transforming growth factor (TGF)-β expression using a polyoxazoline (POx)-poly(lactic-co-glycolic) acid (PLGA) nanovaccine, while modulating the tumor-associated macrophages (TAM) function within the tumor microenvironment (TME) and blocking the anti-programmed cell death protein 1 (PD-1) can constitute an alternative approach for cancer immunotherapy.

Development of Chitosan Particles Loaded with siRNA for Cystatin C to Control Intracellular Drug-Resistant .

The golden age of antibiotics for tuberculosis (TB) is marked by its success in the 1950s of the last century. However, TB is not under control, and the rise in antibiotic resistance worldwide is a major threat to global health care. Understanding the complex interactions between TB bacilli and their host can inform the rational design of better TB therapeutics, including vaccines, new antibiotics, and host-directed therapies.

Preclinical models and technologies to advance nanovaccine development.

The remarkable success of targeted immunotherapies is revolutionizing cancer treatment. However, tumor heterogeneity and low immunogenicity, in addition to several tumor-associated immunosuppression mechanisms are among the major factors that have precluded the success of cancer vaccines as targeted cancer immunotherapies. The exciting outcomes obtained in patients upon the injection of tumor-specific antigens and adjuvants intratumorally, reinvigorated interest in the use of nanotechnology to foster the delivery of vaccines to address cancer unmet needs.

Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators.

A low response rate, acquired resistance and severe side effects have limited the clinical outcomes of immune checkpoint therapy. Here, we show that combining cancer nanovaccines with an anti-PD-1 antibody (αPD-1) for immunosuppression blockade and an anti-OX40 antibody (αOX40) for effector T-cell stimulation, expansion and survival can potentiate the efficacy of melanoma therapy. Prophylactic and therapeutic combination regimens of dendritic cell-targeted mannosylated nanovaccines with αPD-1/αOX40 demonstrate a synergism that stimulates T-cell infiltration into tumours at early treatment stages.

Nanotechnology is an important strategy for combinational innovative chemo-immunotherapies against colorectal cancer.

Colorectal cancer (CRC) is among the five most commonly diagnosed cancers worldwide, constituting 6% of all cancers and the third leading cause of cancer death. CRC is the third and second most frequent cancer in men and women worldwide, accounting for 14% and 13% of all cancer incidence rates, respectively. CRC incidence is decreasing in older populations, but it has been significantly rising worldwide in adolescents and adults younger than 50 years old.

α-Galactosylceramide and peptide-based nano-vaccine synergistically induced a strong tumor suppressive effect in melanoma.

Unlabelled: α-Galactosylceramide (GalCer) is a glycolipid widely known as an activator of Natural killer T (NKT) cells, constituting a promising adjuvant against cancer, including melanoma. However, limited clinical outcomes have been obtained so far. This study evaluated the synergy between GalCer and major histocompatibility complex (MHC) class I and MHC class II melanoma-associated peptide antigens and the Toll-Like Receptor (TLR) ligands CpG and monophosphoryl lipid A (MPLA), which we intended to maximize following their co-delivery by a nanoparticle (NP).

Nanoparticle impact on innate immune cell pattern-recognition receptors and inflammasomes activation.

Nanotechnology-based strategies can dramatically impact the treatment, prevention and diagnosis of a wide range of diseases. Despite the unprecedented success achieved with the use of nanomaterials to address unmet biomedical needs and their particular suitability for the effective application of a personalized medicine, the clinical translation of those nanoparticulate systems has still been impaired by the limited understanding on their interaction with complex biological systems. As a result, unexpected effects due to unpredicted interactions at biomaterial and biological interfaces have been underlying the biosafety concerns raised by the use of nanomaterials.

Modular Assembly of Reversible Multivalent Cancer-Cell-Targeting Drug Conjugates.

Herein is described a new modular platform for the construction of cancer-cell-targeting drug conjugates. Tripodal boronate complexes featuring reversible covalent bonds were designed to accommodate a cytotoxic drug (bortezomib), poly(ethylene glycol) (Peg) chains, and folate targeting units. The B-complex core was assembled in one step, proved stable under biocompatible conditions, namely, in human plasma (half-life up to 60 h), and underwent disassembly in the presence of glutathione (GSH).

Poly(lactic acid)-based particulate systems are promising tools for immune modulation.

Unlabelled: Poly(lactic acid) (PLA) is one of the most successful and versatile polymers explored for controlled delivery of bioactive molecules. Its attractive properties of biodegradability and biocompatibility in vivo have contributed in a meaningful way to the approval of different products by the FDA and EMA for a wide range of biomedical and pharmaceutical applications, in the past two decades. This polymer has been widely used for the preparation of particles as delivery systems of several therapeutic molecules, including vaccines.

A Three-Component Assembly Promoted by Boronic Acids Delivers a Modular Fluorophore Platform (BASHY Dyes).

The modular assembly of boronic acids with Schiff-base ligands enabled the construction of innovative fluorescent dyes [boronic acid salicylidenehydrazone (BASHY)] with suitable structural and photophysical properties for live cell bioimaging applications. This reaction enabled the straightforward synthesis (yields up to 99%) of structurally diverse and photostable dyes that exhibit a polarity-sensitive green-to-yellow emission with high quantum yields of up to 0.6 in nonpolar environments.

Regulatory aspects on nanomedicines.

Nanomedicines have been in the forefront of pharmaceutical research in the last decades, creating new challenges for research community, industry, and regulators. There is a strong demand for the fast development of scientific and technological tools to address unmet medical needs, thus improving human health care and life quality. Tremendous advances in the biomaterials and nanotechnology fields have prompted their use as promising tools to overcome important drawbacks, mostly associated to the non-specific effects of conventional therapeutic approaches.

Translational Peptide-associated Nanosystems: Promising Role as Cancer Vaccines.

Cancer is a heterogeneous disease that results from a multi-step process, being characterized by uncontrolled proliferation, invasion and metastasis. The understanding that tumor cells can be recognized by host immune cells has highlighted the potential advantages of using vaccination purposes to eliminate cancer cells, while avoiding severe side effects associated to conventional cancer treatments. Interesting outcomes have been obtained with the new identified tumor associated antigens (TAAs), including recombinant proteins and peptides.

Antibody oriented immobilization on gold using the reaction between carbon disulfide and amine groups and its application in immunosensing.

Carbon disulfide (CS(2)) can spontaneously react with amine groups to form dithiocarbamates on gold surface, providing the possibility to immobilize some compounds with primary or secondary amine groups in one step. Using this principle, an immunosensor interface prepared for immunoglobulin G (IgG) sensing surface toward anti-IgG has been fabricated for the first time by simply immersing gold slides into a mixed aqueous solution of CS(2) and protein A, followed by incubation in immunoglobulin G solution. The reaction between CS(2) and protein A has been followed by UV-vis spectroscopy, whereas cyclic voltammetry has been employed in the characterization of the modified gold surface with CS(2) and protein A, both methods indicating that protein A immobilization is implemented by CS(2).