A universal monoclonal antibody-aptamer conjugation strategy for selective non-invasive bioparticle isolation from blood on a regenerative microfluidic platform.

Simultaneous isolation of various circulating tumor cell (CTC) subtypes from whole blood is useful in cancer diagnosis and prognosis. Microfluidic affinity separation devices are promising for CTC separation because of their high throughput capacity and automatability. However, current affinity agents, such as antibodies (mAbs) and aptamers (Apts) alone, are still suboptimal for efficient, consistent, and versatile cell analysis. By introducing a hybrid affinity agent, i.e., an aptamer-antibody (Apt-mAb) conjugate, we developed a universal and regenerative microchip with high efficiency and non-invasiveness in the separation and profiling of various CTCs from blood. The Apt-mAb conjugate consists of a monoclonal antibody that specifically binds the target cell receptor and a surface-bound aptamer that recognizes the conserved Fc region of the mAb. The aptamer then indirectly links the surface functionalization of the microfluidic channels to the mAbs. This hybrid affinity agent and the microchip platform may be widely useful for various bio-particle separations in different biological matrices. Further, the regeneration capability of the microchip improves data consistency between multiple uses and minimizes plastic waste while promoting environmental sustainability. STATEMENT OF SIGNIFICANCE: A hybrid affinity agent, Apt-mAb, consisting of a universal aptamer (Apt) that binds the conserved Fc region of monoclonal antibodies (mAbs) was developed. The invented nano-biomaterial combines the strengths and overcomes the weakness of both Apts and mAbs, thus changing the paradigm of affinity separation of cell subtypes. When Apt-mAb was used to fabricate microfluidic chips using a "universal screwdriver" approach, the microchip could be easily tuned to bind any cell type, exhibiting great universality. Besides high sensitivity and selectivity, the superior regenerative capacity of the microchips makes them reusable, which provides improved consistency and repeatability in cell profiling and opens a new approach towards in vitro diagnostic point-of-care testing devices with environmental sustainability and cost-effectiveness.

ß-Cyclodextrin-grafted hyaluronic acid as a supramolecular polysaccharide carrier for cell-targeted drug delivery.

ß-Cyclodextrin (ß-CD) was grafted onto hyaluronic acid (HA) in a single step to generate a supramolecular biopolymer (HA-ß-CD) that was explored for targeted drug delivery applications. Along with its excellent biocompatibility, the prepared HA-ß-CD exhibits not only exceptionally high loading capacity for the model drugs doxorubicin and Rhodamine B through the formation of inclusion complexes with the ß-CD component, but also the capability of targeted drug delivery to cancerous cells with a high level of expression of CD44 receptors, attributable to its HA component. The polymer can release the drug under slightly acidic conditions. With all its attributes, HA-ß-CD may be a promising cancer-cell-targeting drug carrier.

Multifunctional Graphene-Oxide-Reinforced Dissolvable Polymeric Microneedles for Transdermal Drug Delivery.

Dissolvable polymeric microneedles (DPMNs) are promising transdermal drug delivery systems with minimal invasiveness and improved patient compliance. Incorporation of a small amount of graphene oxide (GO) in the biocompatible polymers for microneedle fabrication results in important new DPMN properties, that is, dramatically enhanced mechanic strength (10-17 times at 500 mg/mL GO), improved moisture resistance, self-sterilization, antibacterial and anti-inflammatory properties (demonstrated in vitro), and near-infrared light-activated controlled drug release (demonstrated in vitro and in vivo), which were exploited for the transdermal delivery of the chemotherapeutic, HA15, to melanoma-bearing mouse models. These new properties improve their efficacy of transdermal drug delivery and ease of use, enhance their capability of controlled drug release, enlarge the scope of the polymers that can be used for DPMN fabrication, prevent microbial contamination during storage and transportation, and reduce infection risk in clinical applications.