Yeast Microcapsule-Mediated Targeted Delivery of Diverse Nanoparticles for Imaging and Therapy via the Oral Route

Abstract

Targeting of nanoparticles to distant diseased sites after oral delivery remains highly challenging due to the existence of many biological barriers in the gastrointestinal tract. Here we report targeted oral delivery of diverse nanoparticles in multiple disease models, via a "Trojan horse" strategy based on a bioinspired yeast capsule (YC). Diverse charged nanoprobes including quantum dots (QDs), iron oxide nanoparticles (IONPs), and assembled organic fluorescent nanoparticles can be effectively loaded into YC through electrostatic force-driven spontaneous deposition, resulting in different diagnostic YC assemblies. Also, different positive nanotherapies containing an anti-inflammatory drug indomethacin (IND) or an antitumor drug paclitaxel (PTX) are efficiently packaged into YC. YCs containing either nanoprobes or nanotherapies may be rapidly endocytosed by macrophages and maintained in cells for a relatively long period of time. Post oral administration, nanoparticles packaged in YC are first transcytosed by M cells and sequentially endocytosed by macrophages, then transported to neighboring lymphoid tissues, and finally delivered to remote diseased sites of inflammation or tumor in mice or rats, all through the natural route of macrophage activation, recruitment, and deployment. For the examined acute inflammation model, the targeting efficiency of YC-delivered QDs or IONPs is even higher than that of control nanoprobes administered at the same dose via intravenous injection. Assembled IND or PTX nanotherapies orally delivered via YCs exhibit remarkably potentiated efficacies as compared to nanotherapies alone in animal models of inflammation and tumor, which is consistent with the targeting effect and enhanced accumulation of drug molecules at diseased sites. Consequently, through the intricate transportation route, nanoprobes or nanotherapies enveloped in YC can be preferentially delivered to desired targets, affording remarkably improved efficacies for the treatment of multiple diseases associated with inflammation.

A Proresolving Peptide Nanotherapy for Site‐Specific Treatment of Inflammatory Bowel Disease by Regulating Proinflammatory Microenvironment and Gut Microbiota

“…[13,14] A recent study revealed the potential of Ac2-26 for the treatment of colitis after intraperitoneal or intramucosal injection of Ac2-26 in nanoparticles (NPs). [16][17][18][19][20][21] However, there are still tremendous challenges in the design and development of translational nanovehicles for oral delivery of macromolecular therapeutics, [16,[22][23][24][25] although different nanotherapies have been developed for targeted treatment of IBD. On the other hand, patient-friendly oral delivery is highly preferred for treatment of gastrointestinal and chronic diseases, owing to its convenience, high patient compliance, desirable cost-effectiveness, and good safety profile.…”

A Novel Strategy for Treating Inflammatory Bowel Disease by Targeting Delivery of Methotrexate through Glucan Particles

“…YGPs were labeled with FITC according to the previous study. [ 39 ] Briefly, 1 g of YGPs were incubated in 100 mL of sodium carbonate buffer solution (0.1 m , pH 9.2) for 0.5 h, and FITC dissolved in DMSO (1 mg mL −1 ) was added dropwise with stirring overnight in the dark. Finally, the FITC‐labeled YGPs (denoted as YGPs‐FITC) were collected by centrifugation, and washed well with sterile water, followed by lyophilization.…”

The biological challenges and pharmacological opportunities of orally administered nanomedicine delivery

“…These chitosan-bound particles were more readily transcytosed by M cells, via the ganglioside GM1 receptor. Another example of exploiting the endogenous role of Mcells is the use of yeast capsules containing nanoparticles [95]. Firstly, there are a very limited number of Peyer's patches in the human gut [89] and the total number of M cells on the intestinal surface is estimated at only one millionth the number compared to other epithelial cells [96].…”