Microfluidic platform for combinatorial synthesis and optimization of targeted nanoparticles for cancer therapy.

Taking a nanoparticle (NP) from discovery to clinical translation has been slow compared to small molecules, in part by the lack of systems that enable their precise engineering and rapid optimization. In this work we have developed a microfluidic platform for the rapid, combinatorial synthesis and optimization of NPs. The system takes in a number of NP precursors from which a library of NPs with varying size, surface charge, target ligand density, and drug load is produced in a reproducible manner.

Parallel microfluidic synthesis of size-tunable polymeric nanoparticles using 3D flow focusing towards in vivo study.

Unlabelled: Microfluidic synthesis of nanoparticles (NPs) can enhance the controllability and reproducibility in physicochemical properties of NPs compared to bulk synthesis methods. However, applications of microfluidic synthesis are typically limited to in vitro studies due to low production rates. Herein, we report the parallelization of NP synthesis by 3D hydrodynamic flow focusing (HFF) using a multilayer microfluidic system to enhance the production rate without losing the advantages of reproducibility, controllability, and robustness.

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.

Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles.

Aim: Two unexplored aspects for irinotecan and cisplatin (I&C) combination chemotherapy are: actively targeting both drugs to a specific diseased cell type, and delivering both drugs on the same vehicle to ensure their synchronized entry into the cell at a well-defined ratio. In this work, the authors report the use of targeted polymeric nanoparticles (NPs) to coencapsulate and deliver I&C to cancer cells expressing the prostate-specific membrane antigen.

Materials & Methods: Targeted NPs were prepared in a single step by mixing four different precursors inside microfluidic devices.

Microfluidic technologies for accelerating the clinical translation of nanoparticles.

Using nanoparticles for therapy and imaging holds tremendous promise for the treatment of major diseases such as cancer. However, their translation into the clinic has been slow because it remains difficult to produce nanoparticles that are consistent 'batch-to-batch', and in sufficient quantities for clinical research. Moreover, platforms for rapid screening of nanoparticles are still lacking.

Targeted polymeric therapeutic nanoparticles: design, development and clinical translation.

Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newer generations of targeted and controlled release polymeric NPs are now engineered to navigate the complex in vivo environment, and incorporate functionalities for achieving target specificity, control of drug concentration and exposure kinetics at the tissue, cell, and subcellular levels.

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.

Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles.

The engineering of drug-encapsulated targeted nanoparticles (NPs) has the potential to revolutionize drug therapy. A major challenge for the smooth translation of targeted NPs to the clinic has been developing methods for the prediction and optimization of the NP surface composition, especially when targeting ligands (TL) of different chemical properties are involved in the NP self-assembly process. Here we investigated the self-assembly and properties of two different targeted NPs decorated with two widely used TLs that have different water solubilities, and developed methods to characterize and optimize NP surface composition.

Engineering of self-assembled nanoparticle platform for precisely controlled combination drug therapy.

The genomic revolution has identified therapeutic targets for a plethora of diseases, creating a need to develop robust technologies for combination drug therapy. In the present work, we describe a self-assembled polymeric nanoparticle (NP) platform to target and control precisely the codelivery of drugs with varying physicochemical properties to cancer cells. As proof of concept, we codelivered cisplatin and docetaxel (Dtxl) to prostate cancer cells with synergistic cytotoxicity.

Polymeric nanoparticles for drug delivery.

The use of biodegradable polymeric nanoparticles (NPs) for controlled drug delivery has shown significant therapeutic potential. Concurrently, targeted delivery technologies are becoming increasingly important as a scientific area of investigation. In cancer, targeted polymeric NPs can be used to deliver chemotherapies to tumor cells with greater efficacy and reduced cytotoxicity on peripheral healthy tissues.

Single-step assembly of homogenous lipid-polymeric and lipid-quantum dot nanoparticles enabled by microfluidic rapid mixing.

A key challenge in the synthesis of multicomponent nanoparticles (NPs) for therapy or diagnosis is obtaining reproducible monodisperse NPs with a minimum number of preparation steps. Here we report the use of microfluidic rapid mixing using hydrodynamic flow focusing in combination with passive mixing structures to realize the self-assembly of monodisperse lipid-polymer and lipid-quantum dot (QD) NPs in a single mixing step. These NPs are composed of a polymeric core for drug encapsulation or a QD core for imaging purposes, a hydrophilic polymeric shell, and a lipid monolayer at the interface of the core and the shell.