Despite all the advances seen in recent years, the severe adverse effects and low specificity of conventional chemotherapy are still challenging problems regarding cancer treatment. Nanotechnology has helped to address these questions, making important contributions in the oncological field. The use of nanoparticles has allowed the improvement of the therapeutic index of several conventional drugs and facilitates the tumoral accumulation and intracellular delivery of complex biomolecules, such as genetic material. Among the wide range of nanotechnology-based drug delivery systems (nanoDDS), solid lipid nanoparticles (SLNs) have emerged as promising systems for delivering different types of cargo. Their solid lipid core, at room and body temperature, provides SLNs with higher stability than other formulations. Moreover, SLNs offer other important features, namely the possibility to perform active targeting, sustained and controlled release, and multifunctional therapy. Furthermore, with the possibility to use biocompatible and physiologic materials and easy scale-up and low-cost production methods, SLNs meet the principal requirements of an ideal nanoDDS. The present work aims to summarize the main aspects related to SLNs, including composition, production methods, and administration routes, as well as to show the most recent studies about the use of SLNs for cancer treatment.

Structural maintenance of chromosomes protein 2 (SMC2) is a central component of the condensin complex involved in DNA supercoiling, an essential process for embryonic stem cell survival. SMC2 over-expression has been related with tumorigenesis and cancer malignancy and its inhibition is regarded as a potential therapeutic strategy even though no drugs are currently available. Here, we propose to inhibit SMC2 by intracellular delivery of specific antibodies against the SMC2 protein. This strategy aims to reduce cancer malignancy by targeting cancer stem cells (CSC), the tumoral subpopulation responsible of tumor recurrence and metastasis. In order to prevent degradation and improve cellular internalization, anti-SMC2 antibodies (Ab-SMC2) were delivered by polymeric micelles (PM) based on Pluronic^® F127 amphiphilic polymers. Importantly, scaffolding the Ab-SMC2 onto nanoparticles allowed its cellular internalization and highly increased its efficacy in terms of cytotoxicity and inhibition of tumorsphere formation in MDA-MB-231 and HCT116 breast and colon cancer cell lines, respectively. Moreover, in the case of the HCT116 cell line G1, cell-cycle arrest was also observed. In contrast, no effects from free Ab-SMC2 were detected in any case. Further, combination therapy of anti-SMC2 micelles with paclitaxel (PTX) and 5-Fluorouracil (5-FU) was also explored. For this, PTX and 5-FU were respectively loaded into an anti-SMC2 decorated PM. The efficacy of both encapsulated drugs was higher than their free forms in both the HCT116 and MDA-MB-231 cell lines. Remarkably, micelles loaded with Ab-SMC2 and PTX showed the highest efficacy in terms of inhibition of tumorsphere formation in HCT116 cells. Accordingly, our data clearly suggest an effective intracellular release of antibodies targeting SMC2 in these cell models and, further, strong cytotoxicity against CSC, alone and in combined treatments with Standard-of-Care drugs.

(1) Background: gold nanoparticles (AuNPs) are of particular interest in biomedical research because they possess unique optical properties. In particular, its localized surface plasmon resonance is widely used for photothermal therapy and for detecting molecular interactions at nanoparticle surfaces. To enhance circulation time and biocompatibility, nanoparticles are often coated to shield their hydrophobic character. (2) Methods: we explored the seed-growth method to coat AuNPs with phospholipids to improve colloidal stability. (3) Results: various charged phospholipids were tested, and particle size and zeta potential were characterized. The monodispersity of the coated nanoparticles strongly depends on the narrow size distribution of both gold nanoparticles seeds and lipid vesicles. Achieving stable coated AuNPs with zwitterionic lipids such as phosphatidylcholine was challenging, whereas coatings containing phosphatidylglycerol did not compromise nanoparticle stability. (4) Conclusions: coating AuNPs with phospholipids via the seed-growth method has potential but requires further optimization to improve reproducibility and achieve stable nanoparticles with near-neutral surface charge.

Silica particles are promising multifunctional drug delivery platforms; however, when in contact with blood or other biological fluids, proteins rapidly adsorb to their surface, forming the protein corona that modulates their biological interactions. In this study, silica microparticles were coated with lipid bilayers using two approaches: the lipid film hydration method and the on-particle solvent-assisted lipid coating (OPSALC) technique. We investigated how phospholipids with varying charges (zwitterionic, anionic, and cationic) and membrane phase influence coating formation and protein corona adsorption. The coating coverage and aggregation were characterized by fluorescence microscopy. The lipid film hydration method enabled coating with a broad range of lipids, but was highly dependent on the membrane phase and electrostatic interactions between lipid head group and particle surface. Pure anionic coatings were not achievable with this method; however, when combining the OPSALC method with a pre-silanization step, fully anionic coatings of silica microparticles were successfully obtained. Assessment by SDS-PAGE revealed differences in protein corona profiles modulated by the lipid compositions on the particles’ coatings. Overall, this study highlights the dependence of coating formation and protein corona composition on the phospholipid coatings’ properties.

Activation of the STING pathway is crucial for antitumor immunity, but targeting the STING receptor therapeutically remains a challenge due to inefficient intracellular delivery of its agonists. Here, we explore the potential of FDA-approved lipid nanoparticles (LNPs), used in Spikevax COVID-19 vaccine, to increase the uptake of a cGAMP analog (cG^sA^sMP) to dendritic cells (DCs) and induce cell activation. These LNPs are highly reproducible, effectively encapsulate cG^sA^sMP, and are easily scalable. We show that cG^sA^sMP LNPs are efficiently internalized by DCs in vitro, and the cargo is released into the cytoplasm, which strongly enhances STING activation and DC maturation. Furthermore, we introduce an in vitro model of tumor-associated human DCs that mimics the DC phenotype observed in cancer patients. When applied to this model, cG^sA^sMP LNPs successfully reprogram tumor-associated DCs toward an active state, thus emphasizing their potential for cancer immunotherapy. Overall, this work presents a novel and scalable approach utilizing LNPs to deliver cyclic dinucleotide-based STING agonists to counteract immune suppression in cancer.