Multi-stage delivery nano-particle systems for therapeutic applications

Abstract

Background The daunting task for drug molecules to reach pathological lesions has fueled rapid advances in Nanomedicine. The progressive evolution of nanovectors has led to the development of multi-stage delivery systems aimed at overcoming the numerous obstacles encountered by nanovectors on their journey to the target site. Scope of Review This review summarizes major findings with respect to silicon-based drug delivery vectors for cancer therapeutics and imaging. Based on rational design, well established silicon technologies have been adapted for the fabrication of nanovectors with specific shapes, sizes, and porosities. These vectors are part of a multi-stage delivery system that contains multiple nano-components, each designed to achieve a specific task with the common goal of site-directed delivery of therapeutics. Major Conclusions Quasi-hemispherical and discoidal silicon microparticles are superior to spherical particles with respect to margination in the blood, with particles of different shapes and sizes having unique distributions in vivo. Cellular adhesion and internalization of silicon microparticles is influenced by microparticle shape and surface charge, with the latter dictating binding of serum opsonins. Based on in vitro cell studies, the internalization of porous silicon microparticles by endothelial cells and macrophages is compatible with cellular morphology, intracellular trafficking, mitosis, cell cycle progression, cytokine release, and cell viability. In vivo studies support superior therapeutic efficacy of liposomal encapsulated siRNA when delivered in multi-stage systems compared to free nanoparticles.

Particle platforms for cancer immunotherapy

“…[80][81][82] Using polystyrene particles, Foged et al 76 reported that the optimal particle size for uptake by human blood-derived DCs was 0.5 µm, with uptake predominantly occurring for particles 0.5 µm and smaller. DC uptake of polystyrene particles larger than 1 µm was, however, enhanced by modifying the particles to have a cationic surface charge.…”

Nanomedicine concepts in the general medical curriculum: initiating a discussion

“…17,18 Both are examples of what are known as "first generation" nanocarrier-based drug delivery systems, where tumors passively are targeted as a consequence of the enhanced permeation and retention effect. [19][20][21] In addition to first-generation systems, "second generation" and "third generation" nanocarrier-based drug delivery systems (designed to accomplish more deliberate, active targeting of cancerous cells) continue to be developed for clinical use. 4,11,12,18,[22][23][24][25][26][27] While the preponderance of current research and clinical applications in nanomedicine is in the area of oncology and enhanced therapies for malignant solid tumors, [25][26][27][28][29][30] a range of other efforts also are ongoing.…”

A functional nanocarrier that copenetrates extracellular matrix and multiple layers of tumor cells for sequential and deep tumor autophagy inhibitor and chemotherapeutic delivery

“…However, smaller particle sizes (< 100 nm) are required for better tumor penetration. [25][26][27][28] To balance this contradiction, large-to-small size variable nanocarriers have been designed. 29 The small-sized nanocarrier can penetrate into deep tumors based partly on passive physical diffusion along the pore within the ECM, but the MLTC still limits its penetration capability.…”