On‐Chip Self‐Assembly of a Smart Hybrid Nanocomposite for Antitumoral Applications

Abstract

A hybrid nanocomposite comprised by porous silicon nanoparticles and a stimuli responsive polymeric material, polyethylene glycol‐block‐poly(L‐histidine), is spontaneously formed by nanoprecipitation in a flow‐focusing microfluidic chip. The nanocomposite presents a novel hybrid compound micelle structure with a great robustness for therapeutic applications. Therefore, the nanocomposite is developed and tested as a “smart” multistage drug delivery system (MDDS) in response to some of the current problems that cancer treatment presents. Based on the stimuli‐responsive behavior of the nanocomposite, a chemotherapeutic agent is successfully loaded into the nanosystem and released upon changes in the pH‐values. The nanocomposite demonstrates enhanced stability in plasma, narrow size distribution, improved surface smoothness, and high cytocompatibility. Furthermore, the nanocomposite presents reduced nanoparticle internalization by phagocytic macrophage cells and pH‐dependent cell growth inhibition capacity. Overall, the developed hybrid nanocomposite shows very promising features for its further development as a “smart” pH‐responsive MDDS.

Tailoring Porous Silicon for Biomedical Applications: From Drug Delivery to Cancer Immunotherapy

“…The PSi for constructing drug delivery systems are mostly (quasi) spherical shaped micro‐ and nanoparticles due to their wide applicability and easiness of fabrication. For example, (quasi) spherical PSi micro‐ and nanoparticles were either applied directly or formulated into micro‐ or nanocomposites to enhance the intestinal absorption of oral delivered small molecules (indomethacin and 5‐flurorouracil), peptides (glucagon‐like peptide‐1 (GLP‐1), peptide tyrosine 3–36), and proteins (insulin),[4g,13] and they were also constructed into nanocomposites for the intravenous delivery of chemotherapeutics (methotrexate (MTX) and sorafenib (SFN)) for cancer therapy . In the last decade, several novel “top‐down” and “bottom‐up” approaches have been developed to fabricate spherical PSi particles.…”

“…For example, the unique geometry of discoidal PSi microparticles enabled them to sequentially overcome the biological barriers that particles encountering from the intravenous administration site to the disease site, i.e., tumors;[4j] the surface modification of PSi nanoparticles with polyethylenimine (PEI) contributed to the sustained delivery of small interfering RNA (siRNA) to human breast cancer cells; and the physical encapsulation of PSi nanoparticles in acid‐degradable acetalated dextran (AcDX) facilitated the simultaneously loading of multiple chemotherapeutics into the nanocomposites for combination cancer therapy. [14b]…”

Microfluidic Generation of Nanomaterials for Biomedical Applications

“…Using a similarly designed microfluidic chip, Herranz‐Blanco et al developed an intelligent multistage drug delivery system based on PSNPs. Owing to the high mixing efficiency provided by the microchip, the nanocarriers possessed favorable monodispersion, improved surface smoothness, and thus exhibited enhanced stability in plasma . In another study, Fontana et al used microfluidic technology to decorate cancer cell membrane on the surface of PSNPs for cancer immunotherapy.…”

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

“…[24] Passive-stimuli responsiveness refers to how by applying the physiological changes, the nanoparticle will have a corresponding transformation, thus causing the release of the drugs. For example, considering the pH difference between the extra-and intra-cellular environments, several systems that have responded to low pH conditions were created by different methods, including pH sensitive polymer coatings, [51] conjugation of pH-sensitive chemical bonds, [52] and pH-responsive valve cappings. [53] Other strategies, such as using of DNA as molecular keys to assemble and transform colloidal nanoparticle systems, the conformation of which can be transformed in response to DNA via a toe-hold displacement mechanism and further meditate the cellular−particle interactions for navigating complex biological environments by changing the morphology of nanoparticles, the cellular uptake from glioma U87-MG cells can thus be enhanced up to 2.5 folds than conventional systems.…”